Health Risks and Benefits of Chickpea (Cicer arietinum) Consumption

Subscriber access provided by CORNELL UNIVERSITY LIBRARY

Review

Look Insight: Health Risks and Benefits of Chickpea (Cicer arietinum) Consumption Rinkesh Kumar Gupta, Kriti Gupta, Akanksha Sharma, Mukul Das, Irfan Ahmad Ansari, and Premendra D. Dwivedi J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.6b02629 • Publication Date (Web): 25 Oct 2016 Downloaded from http://pubs.acs.org on October 29, 2016

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Journal of Agricultural and Food Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 69

1

Journal of Agricultural and Food Chemistry

Title page:

2

Look Insight: Health Risks and Benefits of Chickpea (Cicer arietinum) Consumption

3

Rinkesh Kumar Gupta1,2, Kriti Gupta1, Akanksha Sharma1,3, Mukul Das1, Irfan Ahmad

4

Ansari2, Premendra D. Dwivedi*

5

Affiliation:

6

1

Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute

7

of Toxicology Research (CSIR-IITR), Vish Vigyan Bhawan, 31, Mahatma Gandhi Marg,

8

Lucknow-226 001, Uttar Pradesh, India.

9 2

10

Department of Biosciences, Integral University, Kursi Road, Lucknow-226026, India

11 3

12

Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR campus Lucknow

13 14 15 16 17 18 19 20 21 22 23

*To whom correspondence should be addressed Dr. Premendra D. Dwivedi, Principal Scientist, Food Toxicology Laboratory, Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vish Vigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow-226 001, Uttar Pradesh, India. Email: [email protected]; [email protected] (P. D. Dwivedi) Tel: +91 522 2620107, 2620106, 2616191 Fax No. +91 522 2628227 Running Title: Health effects of chickpea consumption.

24 25 26

1 ACS Paragon Plus Environment


27

Abstract:

28

Chickpeas (CPs) are one of the most commonly consumed legumes especially in the

29

Mediterranean area as well as in the western world. Being one of the most nutritional elements of

30

the human diet, CP toxicity and allergy have raised health concern. CP may contain various anti-

31

nutritional compounds, including protease inhibitors, phytic acid, lectins, oligosaccharides and

32

some phenolic compounds that may impair the utilization of the nutrients by people. Also, high

33

consumption rate of CPs have enhanced the allergic problems in sensitive individuals as it

34

contains many allergens. On the other hand, beneficial health aspects of CPs consumption have

35

received attention from researchers, recently. Phytic acid, lectins, sterols, saponins, dietary

36

fibers, resistant starch, oligosaccharides, unsaturated fatty acids, amylase inhibitors and certain

37

bioactive compounds such as carotenoids and isoflavones have shown the capability of lowering

38

the clinical complications associated with various human diseases. The aim of this article is to

39

unravel the health risks as well as health promoting aspects of CPs consumption and try to fill

40

the gaps that currently exist. The present review also focuses on the various prevention strategies

41

to avoid health risks of CPs consumption using simple but promising ways.

42

Keywords: Chickpeas; Allergens; Isoflavones; Protease inhibitors; Phenolic compounds

43 44 45 46 47 48 49 2 ACS Paragon Plus Environment

Page 2 of 69

Page 3 of 69


50

Introduction

51

Health concern caused by legume consumption is a growing subject in the developed as well as

52

in developing countries.1 Several reports demonstrating both adverse and beneficial health

53

impacts have been attributed to legume intake. Among leguminous foods, chickpea (Cicer

54

arietinum L.) also called Garbanzo beans is one of the oldest valuable source of protein and a

55

main source of human nutrition. Chickpeas (CPs) produce their offspring from grains and have

56

mainly two varieties namely “Kabuli” and “Desi” type. CPs are used in several ways such as

57

whole seeds as well as spilt seeds in two that is called “dal” and many other types of traditional,

58

fermented, deep fried, sweetened and puffed products, especially in India, Spain and some other

59

developing Mediterranean countries. CPs are the world’s third most essential food legume as it is

60

currently grown on about 11.5 million hectares (ha) across the world, with a total production of 9

61

million tons.2 The energy value produced by Kabuli variety is more (365 kcal/100 g) than Desi

62

variety grains (327 kcal/100 g).3 Energy is often measured as gross energy or as a caloric value

63

(Kcal/100 g) and refers to the amount of energy contained in a food. The WHO, 2003

64

recommends high consumption of low energy containing foods that are rich in non starch

65

polysaccharides present in CPs, other vegetables and fruits. Further, beans, lentils and CPs are

66

recommended as an important part of a healthy diet for all the Australians as they contain fibre,

67

necessary vitamins and minerals. CPs are also a rich source of protein, hence included in the

68

meat and fish groups of Australians food.4 According to “Dietary Guidelines for Americans” an

69

intake of 3 cups of legumes including CPs in a week is recommended for those who consume

70

approx. 2,000 kcal/day energy value.5 The “Mediterranean Diet” has been adopted as a pattern of

71

eating in the olive growing areas of the Mediterranean region such as Cyprus, Croatia, Spain,

72

Greece, Italy, Morocco, and Portugal. This kind of diet is based on the consumption of food



73

products based on plants. The Mediterranean Diet recommend the consumption of legumes more

74

than two portions/week to minimize the risk factor and rate of cardiovascular diseases, cancer, as

75

well as the incidence of age associated diseases.6 According to United States Department of

76

Agriculture, National Nutrient Database, one cup of cooked CPs serves 269 calories, 45 g of

77

carbohydrate, 15 g of protein, 13 g of dietary fiber and 4 g of fat. Moreover, dietary consumption

78

of six food legumes namely dry beans, chickpea, cowpea, lentils, faba beans and pigeon pea

79

comes to about 6.8 kg/year per capita in the world.2

80

Despite of immunological and toxicological responses, CPs have several valuable health benefits

81

concerning the management of several diseases. This review primarily focuses on beneficial as

82

well as deleterious health effects of CPs consumption together at the same platform. This article

83

provides an overview of health benefits and possible health troubles coupled with description of

84

nutraceutical and toxic components of CPs.

85

Potential health benefits caused by nutraceutical components of chickpea

86

CPs are excellent food choice due to their health promoting components, including vegetable

87

protein, complex carbohydrate, dietary fibres, vitamins, minerals, oligosaccharides, isoflavones,

88

phospholipids, antioxidants, hence it is considered as obligatory constituent of a healthy diet

89

because its regular consumption has been found to have protective effects against various

90

diseases. Recently, several bioactive compounds of CPs have been investigated for their health

91

supporting aspects. These compounds included certain antinutritional compounds, phenolic

92

compounds including flavonoids, phenolic acids and isoflavones, bioactive peptides with

93

antioxidant, anti-cancerous as well as anti-hypertensive property, non digestible carbohydrates

94

such as dietary fibers and resistant starch, carotenoids and phytosterols. These compounds have


Page 4 of 69

Page 5 of 69


95

been found to be associated with the management of clinical complications associated with

96

several diseases such as diabetes, obesity, cancer, osteoporosis and cardiovascular diseases

97

(Table 1).

98

Chickpeas antioxidants

99

Of late, antioxidant property of CPs has been extensively studied due to presence of numerous

100

bioactive compounds including peptides and polyphenolic compounds with antioxidative

101

potential. Recently, two novel anti-oxidant peptides (P3 and P8) were isolated from enzymatic

102

hydrolysis of CPs protein concentrate. The molecular masses of P3 and P8 peptides were 327, 33

103

and 402, 49, respectively represented by Asp-His-Gly and Val-Gly-Asp-Ile amino acid

104

sequences. The P8 peptide exhibited higher anti-oxidant property than P3 peptide, but its clinical

105

relevance is yet to be explored.7 Further, four antioxidant peptides belonging to legumin seed

106

protein with the sequences of ALEPDHR, TETWNPNHPEL, FVPH and SAEHGSLH have been

107

identified in CPs protein hydrolysate. These purified peptides along with CPs protein hydrolysate

108

were studied for their antioxidant activity in CaCo 2 cells. To measure the antioxidant activity,

109

cells were exposed with either 0.5 mg/ml dose concentration of CPs protein hydrolysates or 0.3

110

mg/ml dose concentration of each peptide fraction and antioxidant potential was measured after

111

60 min. As outcomes, within peptide fractions containing TETWNPNHPEL, FVPH and

112

SAEHGSLH showed a significant increased cellular antioxidant activity compared to chickpea

113

hydrolysate protein, while peptide with ALEPDHR sequence did not show significant

114

differences.8 In future, determination of dietary relevance of these purified peptides should be

115

taken into consideration.



116

Furthermore, phenolic compounds have been recognized as a health promoting factor due to their

117

antioxidant property. CPs contain considerable amounts of phenolic compounds and

118

anthocyanins with the antioxidant properties that included flavonols, flavone glycosides and

119

oligomeric as well as polymeric proanthocyanidins, cinnamic acid, salicylic acid,

120

hydroxycinnamic acid, p-coumaric acid, gallic acid, caffeic acid, vanillic acid, ferulic acid, anise

121

acid, tannic acid, isoferulic acid, piperonyl and chlorogenic acid.9 Most of these compounds have

122

been only tasted for in vitro, cell free assays, however their dietary relevance should be

123

determined in future. Another class of phenolic compounds found in CPs are known as

124

isoflavones, which have many biological roles such as antioxidant, estrogenic, antifungal, and

125

antibacterial activities.10 Several polyphenolic compounds were identified individually and their

126

concentration was also determined in a recent study (Table 2A). Among them, concentration of

127

syringic acid followed by protocatechuic acid was found to be higher. According to the literature,

128

analysis of total phenolic content (TPC) as well as total flavonoids content (TFC) is essential

129

aspect as the amount of these compounds is directly proportional to the antioxidative potential of

130

any food.11 Therefore, the antioxidant capacity of different CPs varieties varied as TPC and TFC

131

are found at different levels in different varieties of seeds. The TPC and TFC of colored CPs

132

were found to be higher than cream and beige color seeds. Thus, CPs seeds having a colorful

133

coatings exhibit higher levels of antioxidant activity, making it more of a functional food in

134

addition to providing dietary proteins.11 The antioxidant capacity of CPs may be influenced by

135

the types of domestic processing employed prior to its consumption. During various steps of

136

processing, a significant decrease or increase may appear in either polyphenolic content of CPs

137

(Table 2B). The level of TPC is found in the range of 203-255 mg/100 g and 101-178 mg/100 g

138

for desi and kabuli chickpea varieties, respectively.12 The TPC and TFC content may vary


Page 6 of 69

Page 7 of 69


139

depending upon CP varieties, quantitative protocols as well as on growing conditions. In a recent

140

study, TPC of native CP was recently reported to have 1.54 mg/g that increased by pressure

141

cooking (53%), open pan boiling (64%) and microwave heating (more than 2 fold increase). In

142

contrast to TPC, TFC of CP that was 1.47 mg/g got significantly reduced by pressure cooking

143

(80%), open pan boiling (84%) and microwave heating (78%). However, impact of sprouting

144

and roasting on the TPC and TFC content of native CP were not having any significant

145

differences (Table 3).13 It is suggested that soaking at room temperature for 22 h followed by

146

steaming for 1 h is the best method for retaining polyphenolic contents of CP.14 Due to biological

147

significance, it must be emphasized that bioactive compounds must be retained even after CP

148

processing.

149

To exert their potent effect on human health, knowledge regarding the bioavailability of these

150

phenolic compounds is essential observation that depends upon the release of these compounds

151

from food sources. Therefore, more efforts are going on for phenolic compounds from food

152

regarding their bioavailability, metabolism as well as mechanistic aspects. Bioaccessible TPC,

153

TFC as well as individual phenolic compounds present in CPs are influenced by domestic

154

processing as listed in Table 2C. Tables of phenolic profile demonstrate that certain compounds

155

such as p-coumaric acid, salicylic acid, t-cinnamic acid do not appear in the detectable range,

156

whereas appearances of these compounds occur during the selective heat processing type.

157

Studies are needed to investigate the reaction process and participating compounds in the

158

formation of these phenolic products during specific processing. Bioaccessibility of phenolic

159

compounds present in CP has been found to be lower as CP contains considerable amount of

160

these compounds. Therefore, more attention is needed towards the development of new

161

processing methods so that the bioavailability of these compounds could be significantly 7 ACS Paragon Plus Environment


162

increased. Since, colored CP possess higher antioxidant compounds, future efforts should be

163

made to ensure that these can be used for the management and prevention of degenerative

164

diseases.

165

Management of diabetes and obesity

166

People suffering from diabetes must control their glycemic conditions, i.e. their blood glucose

167

level. The relative ability of different foods to raise the level of glucose in blood is known as

168

“glycemic index” (GI) of corresponding foods. The GI value of any food helps us to choose the

169

sources of carbohydrates causing a slow release of glucose after a meal. Among the numerous

170

starchy foods, generally beans and pulses have the lowest GI that makes them a suitable source

171

of energy for diabetic patient. Such nutrient sources with lower GI may have a crucial role in the

172

regulation of glycemic condition and insulin secretion in type 2 diabetic patients. CPs starch is

173

more resistant to intestinal digestion due to its extensive polymerization property resulting in

174

lower availability of glucose that causes slower entry into bloodstream and reduced demand of

175

insulin.15,16 This has been clearly demonstrated in case of diabetic rats as feeding of aqueous and

176

methanolic extracts of CP seeds with dose of 400 mg/kg caused significant blood glucose and

177

triglyceride levels reduction, respectively.17 Since, antinutritional compounds have toxic effects,

178

some of these from CP such as phytic acid, lectins and amylase inhibitors may also impair the

179

starch digestion, consequently leading to lower GI in the small intestine (Table 4).18 They

180

inactivate the amylase activity following different mechanisms. e.g., on one side PA binds with

181

Ca2+ required for the stabilization of amylase activity, while on the other side, it binds with

182

starch resulting into its inaccessibility for the digestive enzymes. Apart from impaired starch

183

digestion, PA may regulate blood glucose level by delaying in gastric emptying. Similarly,

184

lectins also lower blood glucose level as it binds with and disrupt intestinal mucosal cells leading 8 ACS Paragon Plus Environment

Page 8 of 69

Page 9 of 69


185

to hindrance in nutrient absorption (Table 4). Sprouted CPs with increased phenolic content have

186

shown inhibitory potential against key enzymes namely α-glucosidase and α-amylase associated

187

with type-2 diabetes, suggesting that novel health promoting factors may be generated during

188

seed metabolism.19 In future, isolation and characterization of such novel compounds and

189

metabolomics should be performed. Considering these anti-diabetic effects, CPs may be

190

considered as a chief and risk-free source of energy for the diabetic individuals. Also, such

191

bioactive compounds from CPs may be used in the development of anti-diabetic products (Figure

192

1).

193

Obesity is a major health concern for the majority of people around the globe. It is associated

194

with the risk for a variety of diseases and health complications. The causal factors for obesity are

195

multiple but among them the type and amount of eaten food are most obvious factor. Due to

196

healthy nutrients, legumes have beneficial role in the management of body weight. Pulses are

197

rich sources of dietary fiber, which is known for the protective role in the development and

198

management of obesity.20 High dietary fiber intake has several attributes such as longer eating

199

times because of lower energy density of high-fibre foods, delayed gastric emptying,

200

consequently sends earlier signs of fullness, earlier satiety due to feeling of gastric and intestinal

201

bulking, reduced absorption of nutrients and effects of short-chain fatty acids on hunger and

202

satiety. In a human study, effects of two hypocaloric diets (legume-restricted- vs. legume-based

203

diet) on metabolic and inflammatory changes, accompanying weight loss has been investigated.

204

In this study, thirty obese subjects, 17 men and 13 women were randomly distributed into two

205

groups which were assigned to two different calorie-restricted dietary treatments for 8 weeks: a

206

legume-restricted diet as a control diet or a legume-based diet with 4 servings/week (1 serving=

207

100 gm) of traditional Spanish non-soybeans legumes that included lentils, chickpeas, peas and 9 ACS Paragon Plus Environment


Page 10 of 69

208

beans. As outcomes, the L-diet was the only dietary approach inducing a significant reduction in

209

body weight, systolic BP measurements, total cholesterol, LDL and HDL concentrations.21 In an

210

animal study, increase in the body weight was successfully prevented by CP supplementation of

211

high fat diet fed rats. Rats were randomly assigned to 3 groups and diets containing normal fat,

212

high fat and high fat supplemented with chickpea were given for 8 months. Addition of 10 %

213

(w/w) CPs to the high fat diet reduced the weight gain from 6 months to the end of the

214

experiment. In addition, chickpea treatment resulted in 45% decrease in the serum TAG, 23%

215

decrease in LDL, 35% rise in HDL and 30% reduction in LDL/HDL compared to the high fat

216

diet fed group.22 Therefore, CP based diet may be considered as a healthy food for the

217

management of obesity.

218

Management of cancer and cardiovascular diseases

219

CPs contains numerous bioactive compounds that have shown their anti-cancerous potential

220

following different mechanism. The C-25 known as antifungal proteins of CP recently proved as

221

a potent anti-mycotic as well as anti-proliferative agent against human oral carcinoma cell line at

222

the concentration of 37.5 ߤg/mL by targeting p38ߙ MAP kinase.23 Future in vivo animal studies

223

as well as human studies are needed to investigate the stability and tissue specific anti-cancerous

224

activity within biological condition. Epidemiological studies have documented a low rate of

225

colon cancer in population with higher legume consumption. In this context, a major sterol

226

present in CP namely β-sitosterol (0.2% w/v) treatment up to 28 weeks in comparison to 0.9%

227

NaCI solution (control group) has been found to reduce chemical induced colon tumor counts in

228

rat.24 Further, anti-cancerous potential of CP flour in comparison to soy flour has been

229

investigated. In this study, mice with colon cancer induced by a carcinogen azoxymethane were

230

fed with 10% (w/w) CP (w/w), 10% (w/w) soy, 10% (w/w) mixed (soy and CP flours) of diet in 10 ACS Paragon Plus Environment

Page 11 of 69


231

separate groups for ten weeks. As outcomes, supplementation with 10% CP and 10% soy flours

232

had resulted in significant suppression of colonic aberrant crypt formation by 64% and 53%,

233

respectively. Combining soybean and CP flour had not shown any additional or synergistic

234

efficacy as compared to the administration of individual flours.25 The CP albumin hydrolysate

235

exhibit potent anti-tumor activity even after the tumor induction, administration of CP albumin

236

hydrolysate by gavage each day for 12 days at different doses of 50, 100, and 200 mg/kg, caused

237

significant reduction in tumor volume in mice after the 10th day of the CAH treatment.26

238

Considering the above discussed properties, CPs may serve as a functional food for the risk of

239

various types of cancer but anti-cancerous potential of these bioactive compounds should be

240

investigated at physiological conditions after CP ingestion.

241

Similar to cancer, cardiovascular disease (CVD) is another leading cause of mortality in the

242

developed and developing countries. In the context of CVD management, split legumes provide

243

various health promoting factors. Since, hypercholesterolaemia i.e. high plasma cholesterol level

244

is a characteristic of CVD, the impact of dietary fiber on the level of serum cholesterol have

245

received tremendous attention. The beans and other pulses, may contribute in lowering of the

246

plasma cholesterol level as they are a rich source of dietary fibers. The potent plasma cholesterol

247

lowering ability of dietary 10 % (w/w) CPs has been reported. High fat diet (HFD) supplemented

248

with CPs for eight months has been found to be induced a favorable plasma lipid profile

249

reflecting decreased tri-acyl glycerol (TAG), LDL-cholesterol (LDL-C) and LDL-C:HDL-

250

cholesterol levels in comparison to high fat diet fed rats. HFD-fed rats had higher TAG

251

concentration in muscle and liver, whereas the combination of CPs to the HFD drastically

252

reduced TAG concentration in muscle and liver. Apart from this, activities of lipoprotein lipase

253

in epididymal adipose tissue and hepatic TAG lipase in liver recorded a significant decrease of 11 ACS Paragon Plus Environment


Page 12 of 69

254

40 and 23 %, respectively in HFD-CP fed compared with those in HFD rats.22 Possible

255

protective and therapeutic effects of a diet containing heated chickpea in a dietary induced rat

256

model of hypercholesterolemia have been demonstrated. In type II hyperlipoproteinemic rats,

257

elevated lipid profiles were improved in the hypercholesterolemic rats receiving legume diets for

258

16 days. Moreover, results had confirmed that the chickpea was more effective than the control

259

diet containing casein in the normalization of triglycerides as well as total and LDL-cholesterol

260

levels in the plasma.27

261

Further, saponins have been extensively discussed due to increasing evidence on their hypo-

262

cholesteromic effect. CPs contain a considerable amount of saponins content i.e. 297 µg/g

263

mainly as saponin B and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyranone (DDMP) saponins.

264

Certain processing methods such as soaking and peeling of chickpeas have been found to cause

265

reduction in the total amount of saponins by 8 %. Subsequently, different cooking conditions

266

also significantly reduced the CP saponins content by 47.8%, 46.2%, 49.4%, 17.27% after

267

microwaving, frying, frying/microwaving and steaming respectively.28 More recently, the anti-

268

hyperlipidemic effect of sprouted CPs was observed in ovariectomy-induced dyslipidemic rats.

269

Dietary supplementation with 20% (w/w) germinated CPs reverses the abnormal lipid profile by

270

including higher high-density lipoprotein (HDL) cholesterol levels in serum and liver,29

271

suggesting that sprouted CPs may offer a better food choice as compared to raw CPs. Therefore,

272

dietary CPs may contribute to minimize the risk of CVD, effectively as its hypocholesteromic

273

effect has been evident in many in vivo experiments. The above discussed findings provide a

274

rational basis for the consumption of CPs as a functional food ingredient, which may be

275

beneficial for improving the hypercholesteromia related health complications.

276 12 ACS Paragon Plus Environment

Page 13 of 69


277

Hypertension prevention and estrogenic activity

278

Hypertension is a hallmark for stroke and other cardiovascular diseases. Among other strategies,

279

angiotensin I-converting enzyme (ACE) inhibitors are considered as a preventive agent in

280

hypertension.30 The ACE inhibitor peptides are anti-hypertensive in nature because ACE causes

281

high blood pressure following conversion of biologically inactive angiotensin I to the activated

282

vasoconstrictor angiotensin II and also inhibits the vasodilator bradykinin (Figure 2).31 CPs may

283

have crucial role in controlling hypertension as CP proteins are a good source of bioactive

284

peptides with inhibitory potential for ACE. In a previous study, four ACE inhibitory peptides

285

with molecular weight of 900 Da and IC50 0.1 mg/ml of each were identified in the CPs protein

286

hydrolysates after enzymatic hydrolysis. Among them, two peptides were found to be inhibited

287

competitively, whereas the other two were uncompetitive inhibitors of ACE (Answer will be

288

given).32 Peptides having higher amino acid residue number are more efficient for ACE

289

inhibition. In another study, protein/peptide profiles of CPs have also been shown to have a rich

290

composition of the small peptides under the molecular weight of 4 kDa in the protein

291

hydrolysates. The protein hydrolysate obtained from chickpea desi verities has been shown

292

higher ACE inhibition with the IC50 of 140 ± 1 µg/ml compared to its digests generated by

293

alcalase/flavourzyme having IC50 of 228 ± 3 µg/ml or papain with the IC50 of 180 ± 1 µg/ml

294

and to CP kabuli type hydrolyzed by gastrointestinal digestion (IC50 of 229 ± 1 µg/ml).33 In

295

addition to peptide, certain phenolic compounds present in CPs have been suggested as a

296

potential candidate for the ACE inhibition. Recently, CP phenolic extracts represented by ferulic

297

acid, p-hydroxybenzoic, protocatechuic, caffeic, chlorogenic and p-coumaric acids, have shown

298

a significant and dose-dependent inhibition of ACE-I. CPs phenolic extract at 40 µg/ml

299

concentrations has been shown to inhibit ACE by 33.2%.34 These bioactive compounds may have 13 ACS Paragon Plus Environment


Page 14 of 69

300

a significant contribution towards the ACE-I enzyme inactivation but their individual potency

301

regarding this is yet to be explored. It must be mentioned here that for peptides to be effective

302

ACE inhibitors, they must escape digestion and enter the circulatory system prior to entering the

303

target cells. Considering this point, further investigations to assess in vivo and clinical

304

antihypertensive potential will be required steps to confirm the discussed findings. In addition,

305

more studies are needed to investigate the optimal conditions required for the production of such

306

promising ACE inhibiting bioactive compounds.

307

Phytoestrogens, a class of chemicals produced by a variety of plants estrogenic isoflavons such

308

as formononetin, biochanin A, genistein and daidzein are currently heralded as offering

309

alternative potential therapeutic agent for serious diseases. For instance, genistein and daidzein

310

both have been found effective in the management of diabetes by acting on peroxisome

311

proliferator-activated receptors and reduces the risk of coronary heart disease by reducing the

312

level of low-density lipoprotein and triglycerides. Genistein is the potential compound found

313

effective in the treatment of cancer by acting on androgen receptor further to inhibit tyrosine

314

kinases.35 Sprouted CPs contain variable amounts of isoflavones such as formononetin, biochanin

315

A and genistein and their contents may increase by the treatment of light. The CP contents of

316

formononetin and biochanin A under light exposure were found to be 154 and 130 times higher,

317

respectively, than in untreated CP seeds. CP sprouts germinated under the light condition exhibit

318

higher amount of isoflavone as compared to other growing conditions.36 CPs isoflavones are of

319

great interest because sprouted CPs are considered as a healthy diet for human consumption,

320

globally. CPs encompass two main estrogenic components of isoflavones namely, formononetin

321

(0.10 ± 0.01 mg/10 g) and biochanin A (0.18 ± 0.02 mg/10 g).31 Recently, sprouted CP seeds

322

have been shown in estrogenic activities i.e. having an action similar to that of an estrogen. The 14 ACS Paragon Plus Environment

Page 15 of 69


323

estrogenic as well as anti-osteoporotic activity of CPs isoflavones has been investigated out in

324

ovariectomized rats. Treatments of ovariectomized rats with sprouted CPs doses of 50 and 100

325

mg/kg/day upto five weeks reflected a significant estrogenic impact on the uteruses, including

326

the increased uterine weight, epithelial height and gland number as well as in the expression of

327

the cell proliferation marker PCNA. The treatments had also improved the secretory profile of

328

ovarian hormones and pituitary gonadotropins. For instance, serum 17β-estradiol level was

329

significantly increased, while serum levels of follicle stimulating and luteinizing hormones were

330

found to be decreased in comparison to ovariectomized rats. In addition, the treatment had

331

significantly attenuated the bone loss and caused an increase in the bone mineral density, bone

332

volume/tissue volume and trabecular thickness.37 In another study, doses of 500 or 1000 mg/kg

333

body weight/day CP extract upto ten weeks have been found to prevent bone loss and

334

osteoporosis

335

RANK/RANKL/OPG system in ovariectomized rats.31 In conclusion, CP isoflavones may be

336

potentially used for the treatment of menopausal symptoms and osteoporosis caused by estrogen

337

deficiency.

338

Toxic components causing adverse health effects

339

Like many other legumes, CP contains variety of toxic substances causing deleterious

340

consequences to the human digestive system. Majority of legume plants, including CPs have the

341

ability to synthesize certain biologically active substances, considered as anti-nutritional

342

compounds. The most widely recognized anti-nutritional compounds from CPs are the protease

343

inhibitors, amylase inhibitors, phytolectins, oligosaccharides, phenolic compounds and

344

other compounds in traces (Figure 3, Table 4).38 Large intake of anti-nutritional compounds

345

causes mild to severe deleterious health effects by impairing the digestion process in human and

by

promoting

the

osteoblast

differentiation


through

regulation

of

few


Page 16 of 69

346

animals. Therefore, the amount of anti-nutritional compounds determines the nutritional quality

347

of CPs.

348

followed by adequate processing, despite certain anti-nutritional compounds may also have

349

beneficial effects on human health (Table 5). Therefore, re-evaluation of nomenclature and

350

important role of these biological compounds should be taken into consideration.

351

Protease Inhibitors (PI)

352

In recent years, several reports are listed on the occurrence, physiological function, mechanism

353

of action, and characterization of protease inhibitors derived from leguminous plants. Trypsin

354

and chymotrypsin inhibitors are widely recognized form of protease inhibitors found in different

355

varieties of CPs.39 Among different CPs varieties, “Desi” and “Kabuli” varieties contain higher

356

amount of trypsin and chymotrypsin inhibitors.40 The protease inhibitors are well defined for

357

their ability to inhibit the proteolytic enzymes that may result in impaired protein digestion. The

358

adverse health effects of protease inhibitors have been observed primarily in animal models.

359

Protease inhibitors have been found to be associated with reduced body growth and pancreatic

360

hypertrophy.41 These complications occur due to the negative feedback mechanism instead of

361

reduced protein digestibility that takes place in the intestine.42 The inactivation of trypsin and its

362

scarcity may happen in the small intestine due to the presence of protease inhibitors.

363

Subsequently, stimulation of intestinal mucosa leads to secretion of cholecystokinin hormone

364

which in turn triggers the pancreas to synthesize more trypsin. Large amounts of sulfur

365

containing amino acids are required for more trypsin synthesis as trypsin is rich in sulfur

366

containing amino acids. Therefore, other body tissue metabolism having involvement of sulfur

367

containing amino acid get affected, which in turn, can contribute to the loss of body weight.

368

Simultaneously, the stress on the pancreas caused by this unusual trend leads to the hypertrophy

Although, in legumes anti-nutritional compounds play contrary health responses


Page 17 of 69


369

and hyperplasia like pathological changes in pancreatic acinar cells, which may further lead to

370

the formation of adenomatous nodules.43

371

To combat the pancreatic hypertrophy and body loss, the elimination or inactivation of PIs is

372

required, which in turn improve the nutritional quality of CPs. The heat-labile nature of legume

373

PIs has been well known and trypsin inhibitor was found to be more vulnerable to heat than

374

cymotrypsin inhibitors.44 To achieve this task, soaking and heat treatments have been found to

375

enhance the nutritional value of several legumes including CPs. Soaking followed by dry heat

376

treatment removes trypsin inhibitor by partial or complete solublization, resulting in removal of

377

trypsin inhibitor with a discarded soaking solution.45 On the other hand, heat treatment

378

frequently inactivates the trypsin inhibitor and volatile substances in CP seeds. Trypsin inhibitors

379

of CP get inhibited by moist heat at 121 °C for 30 minutes or boiling at 100 °C but not by dry

380

heat.46 In addition to these, many other processing methods, including fermentation, autoclaving

381

and germination have been reported to significantly decrease the PI activities in CPs. The water

382

soaking treatments caused significant decrease (approx 14%) in trypsin inhibitor contents in

383

cultivar ICCV10 whereas cooking for 90 sec was able to completely inactivate the trypsin

384

inhibitor. However, germination for 72 hours caused the maximum reduction of trypsin inhibitor

385

to 83.6% in JG74 cultivar. 47 Depending on the present knowledge, it may be concluded that the

386

combination of moist heat treatment and autoclaving may be used as pivotal tools to reduce the

387

amount of PIs, more efficiently.

388

Saponins exert their toxicity by lowering the nutrient availability and decreasing the digestive

389

enzymatic activity that results in inhibition of body growth in animals.48 Tannins are phenolic

390

compounds that reduce the protein digestibility either by formation of less digestible dietary

391

protein complex or inhibition of digestive enzyme.49 CPs contain considerable amount of 17 ACS Paragon Plus Environment


Page 18 of 69

392

saponins (1–5.6 g/100 g) and tannins (0.68 mg/g) of seed dry weight. Chickpea contains mainly

393

βg saponin (a 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one type) and lower amounts of

394

Bb and Be saponins.50 As tannin content, “C- and O-glycosidic derivatives of gallic acid (3,4,5-

395

trihydroxybenzoic acid) has been found in the chickpeas. Tannin content can be reduced by some

396

domestic processing such as roasting (62%) and pressure cooking (more than 2 fold), whereas

397

open pan boiling and microwave heating increase total tannins quantity up to more than 3 fold.13

398

Therefore, processing of CPs should be done before consumption to neutralize these ANCs.

399

Amylase inhibitors (AI)

400

The pancreatic alpha amylase inhibitors have received considerable attention from biochemists

401

and nutritionists ever since their presence was revealed in several legumes, including CPs.

402

However, α-amylase inhibitor activity was lower in CPs compared to other commonly consumed

403

legumes.51 Desi varieties of CPs were found to possess higher amylase inhibitory action than

404

Kabuli varieties when activity was measured in the pancreatic and human salivary amylases.52

405

CP cultivars have been found to have significant variation in the amount of amylase inhibitors

406

(AIs) as it ranged between 11.6-81.4 g/unit in different varieties and also observed that

407

pancreatic amylase was more prone to inhibition as compared to salivary amylase.53 The α-

408

amylase inhibitor may exhibit some adverse effects on mammalian nutrition. The AIs inactivate

409

the amylase by forming an inhibitory complex with the amylase enzyme depending upon pH,

410

ionic strength, temperature, binding duration and inhibitor concentration. Thus, AIs impair the

411

starch digestion and cause reduction in body growth.54

412

Similar to other proteinaceous ANCs, heat-labile nature of CP-AIs are also well-known. The

413

activity of CP-AIs was totally diminished after 10 min boiling of CPs extract.55 Since CP are


Page 19 of 69


414

usually consumed after boiling, therefore practical consequences on starch digestibility do not

415

occur until raw seeds are consumed.

416

Phytolectins and oligosaccharides

417

Phytolectins are a structurally diverse class of sugar binding glyco-proteins found in many

418

leguminous foods. Lectins from legume are known to interact with glycoprotein on the surface of

419

erythrocytes leading to hemagglutination of all human blood types (A, B, AB and O) causing

420

hemolysis and death in rare cases. In seeds, lectins are thought to evolve as storage proteins and

421

have a defensive role in plants, whereas their biological roles are yet to be elucidated. The

422

hemagglutination activity of phytolectin is influenced by several factors such as its molecular

423

property, cell surface property, metabolomics of the cells, cultivar, growing area and collection

424

methods.56,57 Purification and characterization of legume lectins from CPs have been reported

425

earlier.58 The pa2, consisting of two subunits of 23 kDa each, is one of the most abundant lectins

426

found in CPs.59 Hemagglutination activity of CPs lectins is much lower than lentils and peas

427

lectins. Recently, a lectin belonging to plant albumin family has been structurally determined and

428

demonstrated hemagglutination activity in rabbit RBCs.60 Apart from hemagglutination, oral

429

ingestion of lectins cause a decrease in the villi surface area by shielding of brush border

430

membranes in the intestine which renders the gastric secretion required for nutrient absorption as

431

a result. This may cause a pathological condition in the intestine as continuous secretion of

432

gastric enzymes may cause adverse health effects like gastric ulcers. In livestock, feeding of raw

433

pulse seeds impairs the body growth and performance probably due to lectin’s binding affinity to

434

intestinal mucosal cells, leading to altered blood glucose homeostasis.61 Since, there is a risk of

435

food poisoning from consuming unprocessed or less processed pulses, optimization in processing

436

methods should be considered to minimize the risk factor. The lectins are highly sensitive to heat 19 ACS Paragon Plus Environment


Page 20 of 69

437

treatment as they can be completely destroyed after moist heat treatments at 100 °C.62 Dry heat

438

may not completely destroy lectins as some activity still remains even after 18 hours of dry heat

439

treatment at 100 °C. Therefore, it must be emphasized that moist heat treatment should be given

440

to these legumes including CPs prior to consumption.

441

The oligosaccharides belong to raffinose sugar family include stachyose, raffinose and

442

verbascose, causing flatulence in organism. The two sugars stachyose and raffinose together

443

constitute about 37% of the total soluble sugars in CPs.40 Usually, digestive enzymes for these

444

sugars are not found in the human gut therefore, these sugars are decomposed by bacterial

445

fermentation, resulting in production of large amounts of carbon dioxide, hydrogen and lesser

446

amounts of methane gas. Despite their demonstrated health benefits, consumption of pulses in

447

Western countries has traditionally been low. This is, in part, due to the perception that pulses

448

cause flatulence and gastrointestinal upset with the symptoms of abdominal uncomfort and

449

bowel movement. A randomized, double-blind placebo-controlled, cross-over study assessed the

450

impact of 28 consecutive days consumption of 100 g dry weight Kabuli chickpeas, green Laird

451

lentils, and green peas, in comparison to a potato control, on perceived flatulence, abdominal

452

comfort, bowel movements and overall gastrointestinal function in 21 healthy male individuals

453

aged between 19–40. During the treatment period, outcomes revealed minor changes in

454

occurrence and/or severity of flatulence and abdominal discomfort, but no changes in overall

455

gastrointestinal function. Therefore, pulses containing oligosaccharides are well tolerated with

456

negligible perceived changes in flatulence and overall gastrointestinal function when

457

incorporated into the diet of healthy adult males.63 But, large amount of CPs intake may cause

458

abdominal discomfort and gastrointestinal disturbance.

459 20 ACS Paragon Plus Environment

Page 21 of 69


460

Chickpea allergy

461

The incidences of CPs allergy have been reported at different time points from various countries

462

of the world due to global consumption.1 In the few studies carried out by our group, the

463

prevalence of CPs allergy in Indian scenario was found to be higher as compared to other

464

commonly consumed legumes.64,65 CP allergy has been found to be more prevalent (13.2%);

465

followed by green gram (11.8%), egg white (9.2%), red gram/ bean fresh (7.9% each) and bengal

466

gram/ milk/ mustard leaves (6.6% each). The risk due to CPs allergy may get magnified due to

467

cross reactivity of CPs allergens to other legume allergens as some of them share same epitopes

468

or similar sequences and/or structural features.66 CPs cross reactivity with other legumes like

469

peanut, red kidney beans, soybeans and black gram has been reported in our previous studies.64

470

CPs and lentils are the most frequent cause of allergy to legumes in Spanish children that may be

471

explained by exhibited cross reactivity to each other.67 Thus, CPs have the ability to induce

472

allergic symptoms in those susceptible individuals who may be sensitized to other cross reactive

473

legumes. Therefore, the susceptible individuals should be aware of cross reactivities and must

474

take care of all possible routes of exposure.

475

Chickpea allergens

476

The allergic potential of CPs provoked by its allergenic proteins has been well established in

477

humans as well as murine model. In addition to non-allergic proteins, CPs also contain several

478

proteins having IgE binding property that induce the allergic manifestation in sensitive

479

individuals64 and are considered major CPs allergens. CPs allergens belong to the Class 1 food

480

allergens.1 Food allergens of this category have been found to remain undigested in gastric fluid

481

that may lead to sensitization of susceptible individuals. Moreover, seven potent cross-reactive



Page 22 of 69

482

CP allergens have been identified using in silico approach. The identification of these allergenic

483

proteins was carried out on the basis of sequence similarity, structure and physicochemical

484

properties with the known legume allergens. The cross reactivity occurs in four allergens among

485

seven because these four had common sequence as well as structural similarity, with the known

486

allergens.66 The in vitro pepsin digestibility assay of CP proteins revealed that seven proteins of

487

molecular weight approximately 95, 70, 55, 45, 35, 26 and 20 kDa were resistant to digestion in

488

the simulated gastric fluid.64 Thus, these stable proteins may have the potential to elicit allergenic

489

response, independently. Further, immunological characterization of above mentioned proteins

490

using IgE binding property as a tool, was also carried out with sera of humans as well as mice

491

sensitized with CPs.64 CP allergens are derived from two allergenic polypeptides belonging to

492

the family of 2S albumin and 11S globulin seed storage protein.1 The 2S albumin belongs to

493

prolamin superfamily of allergens, whereas 11S globulin belongs to cupin superfamily of

494

allergens. Among them, 2S and Pa2 albumin of CPs were found to provoke the allergic

495

responses in CPs-sensitive individuals.59 Recently, vicilin (50 kDa) and the basic subunit of

496

legumin (20 kDa) were reported as putative CP allergens.68 The purification, characterization and

497

allergenicity assessment of 26 kDa CPs allergen have been carried out69 independently that may

498

be useful for further allergen specific immune therapy treatment. This will also help us to

499

determine the proportion of allergy caused by individual allergen in comparison to crude protein.

500

Therefore, allergenicity assessment of the purified CP allergens is also an important aspect to

501

identify the potential allergy elicitors in CPs. To remove the effector activity of CP allergens,

502

accurate IgE binding sequence (epitope) should be further characterized.

503

Mechanistic aspects of allergy and anaphylaxis caused by chickpea allergens


Page 23 of 69


504

The detailed mechanistic aspects of IgE mediated CP allergy have been explained by a study

505

done by our group.64,69 The IgE mediated reactions

506

hypersensitivity because their consequences appear in less than a minute to hours after the

507

ingestion of allergic foods in susceptible individuals. However, non IgE mediated allergic

508

reactions an outcome of either IgE/IgG mediated allergic reaction or immune complex mediated

509

responses. The allergic reactions and anaphylactic symptoms induced by CP allergens are found

510

to be associated with IgE and IgG antibodies, suggesting that the allergic symptoms appear via

511

IgE as well as IgG mediated allergic reaction.64

512

Like many other food allergens, exposure to 100 µg CP crude protein extract also induce mixed

513

cytokine (Th1/Th2) response in the spleen as higher levels of Th1 and Th2 cytokines (IL-4, IL-6,

514

IL-10, TNF-α and IFN-γ) as well as IL-17 have been found in splenocyte supernatant.64 These

515

inflammatory cytokines may trigger and aggravate the CP allergy and inflammatory responses.

516

The Th2 cytokines produced by CP allergens and some co-stimulatory factors cause class

517

switching to IgE, resulting in more CP allergen specific IgE production. Further, specific IgE

518

bound to the FcεR1 receptor of mast cells or basophiles is termed as sensitization phase. During

519

this phase no allergic symptoms occur. Furthermore, secondary exposure to CP allergens induces

520

cross-linking of IgE bound to mast cells/basophils and results in the release of various chemical

521

mediators such as histamine, mouse mast cell protease (MMCP-1), hexosaminidase, leukotrienes

522

and prostaglandin D2. Recently, Src kinases have been found to be involved in the mast cell

523

activation and degranulation via a signaling cascade triggered by CPs allergen (Figure 4).69

524

These allergic mediators are responsible for onset of allergic and sometimes anaphylactic

525

reactions in the body. CPs allergens exposure also stimulate the production of a chemokine

526

termed as chemokine (C-C motif) ligand-2 (CCL2), which recruits monocytes, memory T cells

are also termed as immediate type



Page 24 of 69

527

and dendritic cells to increase the inflammatory pathogenesis. On the other hand, CPs allergen

528

may also cause eosinophil mediated allergic reactions at various targeted tissues such as intestine

529

and lungs. Thus, CP allergens have potential to elicit the allergic responses using

530

multidimensional mechanism. Till date, studies on the mechanistic aspects of CPs allergy are

531

limited to mast cells and therefore the role of other immune cells including dendritic cells and

532

macrophages causing pathology of CP allergy need to be investigated.

533

Prevention for chickpea allergy associated clinical complications

534

Thermal processing

535

Considering the huge consumption of CPs, more emphasis should be given to the type of

536

processing methods employed that are safer for culinary options. The heat treatment is a pivotal

537

tool for the prevention of adverse health effects caused by allergic components of most of the

538

legumes. It must be mentioned here that most of the allergens are heat resistant, water soluble,

539

resistant to pH and proteases. The uniqueness of allergen such as resistance to gastric digestion,

540

solubility and the permeability of intact protein across the intestinal mucosa may be amended by

541

the applied processing methods.70

542

Multiple immuno-reactive proteins of CP have been reported to retain the same extent of

543

immuno-reactivity even after cooking or boiling. No effect occurs upon 30 min. of boiling on

544

immuno-reactivity of CPs protein, though 60 min. boiling reduced the immuno-reactivity of

545

certain proteins. On the other hand, the impact of autoclaving on CP significantly reduced the

546

number of allergenic proteins. The efficiency of autoclaving regarding the allergenicity

547

attenuation depends upon autoclaving duration as well as extent of applied pressure. An increase

548

in time and applied pressure simultaneously was found to be positively related to the reducing 24 ACS Paragon Plus Environment

Page 25 of 69


549

number of allergenic proteins. Autoclaving for 15 min at 1.2 atm pressure significantly reduced

550

the number of CP allergens, while only few immuno-reactive proteins remain stable even after

551

autoclaving at 2.6 atm for 15 min. If autoclaving time was further increased up to 30 min, it

552

almost degraded the immuno-reactive proteins except only two proteins.71 Therefore, it may be

553

inferred that autoclaving of CPs may reduce the allergenicity, effectively. However, what will be

554

the effect of such harsh conditions on taste of autoclaved CP protein is a matter of further

555

studies.

556

Instant Controlled Pressure Drop Treatment

557

Legumes are the most frequent element of human diet because of their nutritional quality and

558

protein rich content although many legumes are considered a risk factor for toxic and

559

immunogenic responses. Similar to other processing methods, the instant controlled pressure

560

drop (DIC) treatment is considered a preventive tool for reducing the toxic as well as allergic

561

potential of several allergenic foods. The DIC treatment, a food processing method is based on

562

combination of heat and steam pressure treatment. Legume allergies from peanut, lentils and

563

soybeans have been found to be reduced in extent of immuno-reactivity after the DIC treatment

564

DIC treatment at different pressure and time conditions (3-6 bar for 1-3 min).72 In case of CP,

565

DIC treatment was found to be an alternative option to autoclaving for diminishing in vitro IgE

566

binding property. It should be kept in mind that DIC treatment does not affect the total protein

567

content of legume seeds.

568

The Maillard Reaction

569

The Maillard reaction (MR) is a non-enzymatic reaction that takes place between reducing sugar

570

and compounds with a free amino group during thermal processing or long storage of foods. The 25 ACS Paragon Plus Environment


Page 26 of 69

571

impact of MR has been found to be very vague in food allergy as reviewed by Gupta et al.,

572

(2016).73 The MR significantly affects the allergic potential of foods either by

573

inactivation/destruction of epitopes or through generation of new epitopes as well as making

574

cryptic epitopes more accessible. Several studies have revealed that MR induced glycation of

575

legume allergens may reduce its allergenicity in the terms of in vitro IgE binding property.

576

However, some recent studies demonstrate that glycation of food allergens with various reducing

577

sugars attenuates the in vivo allergic responses. Allergenic potential of several purified potent

578

food allergens, including Ara h2/h6, ovalbumin, egg white and β-conglycin allergens have been

579

found to be reduced or inhibited, after glycation.73 For instance, Native Ara h 2/6 (4 mg/ml) in

580

32.5 mM phosphate buffer containing 100 mM NaCl, was heated for 15 min to 110 0C in the

581

presence of 100 mM glucose and found that for most patients this glycation reaction reduced the

582

IgE reactivity of Ara h 2/6 still further compared with thermal treatment alone, and is consistent

583

with the fact that IC50 values for glycated-Ara h 2/6 were 1.3 to 73-fold higher than that of

584

native-Ara h 2/6 (n = 30).74 Further, antigenicity of β-conglycin has been found to be

585

significantly reduced when this allergen was glycated with glucose as compared to dextran,

586

dextran, maltose, lactose, glucose or galactose mixtures (weight ratio 1:1). This reaction was

587

achieved with the incubation at 60 °C and 79 % relative humidity.75 In case of OVA allergen,

588

mannose and glucomannan as glycating agents (condition; 55 0C for 72 h at a 65% relative

589

humidity) have been found to be effective in the suppression of allergic immune responses in the

590

terms of reduced serum levels of MMCP, specific IgG1 and IgG2a.76 Considering these studies,

591

MR may alter the allergenicity of CP allergens also, which calls for investigations.

592 593 26 ACS Paragon Plus Environment

Page 27 of 69


594

Genetic engineering

595

Elimination of allergic proteins by genetic engineering would be economical and potential

596

alternatives to combat the CP allergy. Genetic engineering may offer a potential alternative to deal

597

with allergens as found in many leguminous as well as non-leguminous foods. Genetic engineering

598

also referred as genetic modification is an advancement from conventional plant breeding because it

599

increases the accuracy of gene transfer, and the time to yield the desirable plant is reduced. The

600

major problems with conventional plant breeding are it being less controlled, more random, and

601

simultaneous transfer of several undesirable genes. Recently, site directed mutagenesis and RNA

602

interference (RNAi) techniques have shown their major contribution for the development of a safe

603

delivery method. CRISPR-Cas9 is widely used to produce hypoallergenic foods with reduced

604

allergenicity. We can modify the immuno-dominant epitopes of CP allergens using site directed

605

mutagenesis methods that may result in attenuation of allergic potential of particular CPs allergens.

606

Several studies have demonstrated the potency of this method regarding production of

607

“hypoallergens”. Two of the five IgE binding epitopes of soya allergen (Gly m Bd 30K) could be

608

transformed into non- IgE binding epitopes by single-site amino acid substitutions.77 Hypoallergenic

609

mutants of Ole e 1, the major olive pollen allergen has been produced by one point (Y141A) and two

610

deletions (135 and 140) caused by site-directed mutagenesis.78 Among these, deletion at 135 deletion

611

mutant showed the strongest reduction in the IgE-binding capability of sera from olive pollen-allergic

612

patients. On the other hand, silencing of genes of interest by RNA interference technique may also be

613

a promising strategy for the management of CP allergy. Hypoallergenic CPs can be generated by

614

RNAi technology as expressions of major allergens Mal d 1, Mal d 2 and Mal d 3 were successfully

615

reduced by RNA interference, result in production of hypoallergenic apples.79 In a study carried out

616

by Dodo et al., (2008), it was observed that silencing of the immuno-dominant allergen Ara h 2 leads

617

to its significant reduction and a decrease in peanut allergenicity 80 hence, indicating the possibility of



Page 28 of 69

618

alleviating CP allergy using the RNAi technology. Moreover, it is possible to dramatically reduce the

619

level of specific allergenic proteins in CP by introducing copies of the same gene but in the antisense

620

orientation. For example, the gene encoding the 16 kDa allergen of rice inserted in the antisense

621

orientation significantly reduced levels of 16 kDa protein.81

622 623

Protein Hydrolysis

624

Protein hydrolysis may be employed to reduce the antigenicity and allergenicity.. Allergic

625

reactions caused by certain amino acids sequences may be eliminated using appropriate

626

proteases, resulting into the reduced antigenicity. Hydrolysis of protein causes modification in

627

allergenic peptides so that the altered peptides could not bind with IgE, thereby inhibiting the

628

further sensitization resulting in disappearance of allergic reactions. Protein hydrolysis can be

629

performed either by heating with acid or by addition of proteolytic enzymes. Acid hydrolysis

630

may lead to specific modification in certain amino acid residues i.e. oxidation of

631

cysteine/methionine, destruction of serine/ threonine and conversion of glutamine and asparagine

632

to glutamate and aspartate, respectively. These alterations in important amino acids may reduce

633

the nutrional value of food proteins significantly. Therefore, enzymatic hydrolysis should be

634

preferred over acid hydrolysis to reduce the allergenicity. Enzymatic treatment in combination

635

with heat treatment and ultrafiltration, are considered to be more effective in obtaining suitable

636

protein products for human nutrition with reduced risk of allergenicity.82 Several milk-based

637

hypoallergenic ingredients are manufactured by enzymatic hydrolysis that can be further

638

improved by addition of high pressure treatment. Enzymatic hydrolysis under high hydrostatic

639

pressure of beta-lactoglobulin, was found to reduce the affinity of beta-lactoglobulin to human

640

IgE.83 Further, reduced allergenicity of soybean 2S protein (Kunitz trypsin inhibitor) has been 28 ACS Paragon Plus Environment

Page 29 of 69


641

achieved by partial digestion by peptic hydrolysis for 90 min.84 In a recent study, enzymatic

642

hydrolysis through alcalase and flavourzyme has been found to be effective in attenuating

643

allergenicity of kidney beans, black gram and peanut proteins.85 Furthermore, chickpea protein

644

isolate has been also used for the production of hypoallergenic protein hydrolysates. Most

645

effective reduction in the antigenicity of extensive hydrolyzed chickpea 11S proteins has been

646

observed by sequential treatment with endo- and exopeptidases.86 Such type of specific protease

647

treatment may be employed to produce chickpea protein hydrolysate that could be useful for the

648

elaboration of specialized hypoallergenic food products.

649

Conclusively, CP has several beneficial and few deleterious health effects in humans. CP

650

induced adverse health outcomes are due to the presence of many antinutrients compounds such

651

as protease and amylase inhibitors, phytolectins, phytic acid, some oligosaccharides belonging to

652

raffinose sugar family and few allergens. These toxic and immunogenic components have been

653

shown to be efficiently neutralized by various processing methods employed such as thermal

654

treatment, autoclaving and DIC treatment. In our opinion, approximately 100 g of CPs

655

containing 4 g of amylase inhibitors may be included in the modern diet of diabetic as well as

656

obese individuals. More than 4 g of amylase inhibitors may cause abdominal discomfort and

657

diarrhea. Similarly, particular amount of CP per day containing 3 g of trypsin inhibitor may be

658

included in the modern diet to minimize the risk of cancer but one should also check the toxicity

659

of this particular type of lectin dose in healthy individuals. Considering the existing facts, CPs

660

possesses various components that are studied in animal models for their antinutritional as well

661

as nutritional property. However, more clinical trials of chickpea’s individual components are

662

needed for their toxicity as well as therapeutic potential, so that these me be used in the modern

663

diet to minimize the risk of several diseases. Preservation of these nutraceutical components in 29 ACS Paragon Plus Environment


Page 30 of 69

664

the processed CP has been a big challenge just prior to consumption. Therefore, more attention is

665

needed towards the development of processing methods to retain the bioactive compounds with

666

their biological property, while destroying the harmful antinutrients at the same time.

667

Acknowledgments

668

We are grateful to Professor Alok Dhawan, the Director of the Institute for his keen interest in

669

this study. This work was financially supported by In-Depth Network Project (BSC-0111) of

670

Council of Scientific and Industrial Research (CSIR) and GAP-315 of Indian Council Medical

671

Research, New Delhi. KG and AS are thankful to DST and CSIR, New Delhi for the award of

672

their Women Scientist (WoS) and Senior Research Fellowships. These authors have stated that

673

there is no conflict of interest.

674 675 676 677 678 679 680 681 682


Page 31 of 69


683

References

684

(1) Verma, A. K.; Kumar, S.; Das, M.; Dwivedi, P. D. A comprehensive review of legume

685

allergy. Clin Rev Allergy Immunol. 2013, 45(1), 30-46.

686

(2) Akibode, S.; Maredia, M. Global and regional trends in production, trade and consumption

687

of food legume crops. Department of Agricultural, Food and Resource Economics, Michigan

688

State University, 2011. 87.

689

(3) Maheri-Sis, N.; Chamani, M.; Sadeghi, A. A.; Mirza, A. A.; Aghajanzadeh, G. A. Nutritional

690

evaluation of kabuli and desi type chickpeas (Cicer arietinum L.) for ruminants using in vitro gas

691

production technique. Afr. J. Biotechnol. 2008, 7, 2946–2951.

692

(4) National Health and Medical Research Council. Australian Dietary Guidelines. Canberra,

693

2013. eatforhealth.gov.au.

694

(5) US Department of Health and Human Services, US Department of Agriculture. Dietary

695

Guidelines for Americans. 2005. http://health.gov/dietaryguidelines/dga2005/document.

696

(6) Motohashi, N (ed). Occurrences, Structure, Biosynthesis, and Health Benefits Based on Their

697

Evidences of Medicinal Phytochemicals in Vegetables and Fruits. Polyphenols from the

698

Mediterranean Diet: Structure, analysis and health evidence. Chapter 7. Nova Science

699

Publishers, Inc., 2014, 141 – 209. ISBN 978-1-63117-755-2.”

700

(7) Ghribi, A. M.; Sila, A.; Przybylski, R.; Nedjar-Arroume, N.; Makhlouf, I.; Blecker, C.;

701

Besbes, S. Purification and identification of novel antioxidant peptides from enzymatic

702

hydrolysate of Chickpea (Cicer arietinum L.) protein concentrate. J Funct Foods. 2015, 12, 516-

703

525. 31 ACS Paragon Plus Environment


Page 32 of 69

704

(8) Torres-Fuentes, C.; Contreras Mdel, M.; Recio, I.; Alaiz, M.; Vioque, J. Identification and

705

characterization of antioxidant peptides from chickpea protein hydrolysates. Food Chem. 2015,

706

180, 194-202.

707

(9) Mekky, R. H., Contreras, D. M.; El-Gindi, M. R.; Abdel-Monem, A. R.; Abdel-Sattar, E.;

708

Segura-Carretero, A. Profiling of phenolic and other compounds from Egyptian cultivars of

709

chickpea (Cicer arietinum L.) and antioxidant activity: a comparative study. RSC Adv. 2015,

710

5(23), 17751-17767.

711

(10) Zhao, S.; Zhang, L.; Gao, P.; Shao, Z. Isolation and characterisation of the isoflavones from

712

sprouted Chickpea seeds. Food Chem. 2009, 114, 869–873.

713

(11) Segev, A.; Bandani, H.; Kapulnik, Y.; Shomer, I.; Oren-Shamir, M.; Galili, S.;

714

Determination of Phenolic compounds, Flavonoids, and Antioxidant Capacity in Colored

715

Chickpea (Cicer arietinum L.). J. Food Sci. 2010, 75, S115-S119.

716

(12) Sharma, S.; Yadav, N.; Singh A.; Kumar, R. Antioxidant activity, nuetraceutical profile and

717

health relevant functionality of nine newly developed chickpea cultivars (Cicer arietinum L.).

718

International Journal of Natural Products Research. 2013, 3(2), 44-53.

719

(13) Hithamani, G.; Srinivasan, K. Bioaccessibility of Phenolic compounds from Wheat

720

(Triticum aestivum), Sorghum (Sorghum bicolor), Green Gram (Vigna radiata), and Chickpea

721

(Cicer arietinum) as Influenced by Domestic Food Processing. J. Agric. Food Chem.. 2014, 62,

722

11170−11179.


Page 33 of 69


723

(14) Segev, A.; Badani, H.; Galili, L.; Hovav, R.; Kapulnik, Y.; Shomer, I.; Galili, S. Total

724

Phenolic Content and Antioxidant Activity of Chickpea (Cicer arietinum L.) as Affected by

725

Soaking and Cooking Conditions. Food Nutr Sci. 2011, 2, 724-730.

726

(15) Rivellese, A.; Riccardi, G.; Giacco, A.; Pacioni, D.; Genovese, S.; Mattioli, P. L.; Mancini,

727

M. Effect of dietary fibre on glucose control and serum lipoproteins in diabetic patients. Lancet.

728

1980, 2(8192), 447-50.

729

(16) Osorio-Díaz, P.; Agama-Acevedo, E.; Mendoza-Vinalay, M.; Tovar, J.; Bello-Pérez, L. A.

730

Pasta added with CP flour: chemical composition, in vitro starch digestibility and predicted

731

glycemic index. Cienc Tecnol Aliment. 2008, 6, 6–12.

732

(17) Mustafa, A.; Eltayeb, B. I.; Ali, M. A.; Shaddad, A. S.; Mohammad, H. A. Antidiabetic and

733

hypolipidaemic effects of Cicer arientinum seeds extracts in hyperglycemic and diabetic rats. J

734

Pharm Biomed Sci. 2013, 30(30), 1046-1052.

735

(18) Thompson, L. U. Antinutrients and blood glucose. Food Technol. 1988, 42, 123-32

736

(19) Prathapan, A.; Fahad, K.; Thomas, B. K.; Philip, R. M.; Raghu, K. G. Effect of sprouting on

737

antioxidant and inhibitory potential of two varieties of Bengal gram (Cicer arietinum L.) against

738

key enzymes linked to type-2 diabetes. Int J Food Sci Nutr. 2011, 62(3), 234-8.

739

(20) Blackwood, A. D.; Salter, J.; Dettmar, P. W.; Chaplin, M. F. Dietary fibre, physicochemical

740

properties and their relationship to health. J R Soc Health. 2000, 120, 242–247.

741

(21) Hermsdorff, H. H.; Zulet, M. Á.; Abete, I.; Martínez, J. A. A legume-based hypocaloric diet

742

reduces proinflammatory status and improves metabolic features in overweight/obese subjects.

743

Eur J Nutr. 2011, 50, 61–69. 33 ACS Paragon Plus Environment


Page 34 of 69

744

(22) Yang, Y.; Zhou, L.; Gu, Y.; Zhang, Y.; Tang, J.; Li, F.; Shang, W.; Jiang, B.; Yue, X. Chen

745

M. Dietary CPs reverse visceral adiposity, dyslipidaemia and insulin resistance in rats induced

746

by a chronic high-fat diet. Br J Nutr. 2007, 98, 720–726.

747

(23) Kumar, S.; Kapoor, V.; Gill, K.; Singh, K.; Xess, I.; Das, S. N.; Dey, S. Antifungal and

748

antiproliferative protein from Cicer arietinum: a bioactive compound against emerging

749

pathogens. Biomed Res Int. 2014, 2014, 387203.

750

(24) Raicht, R. F.; Cohen, B. I.; Fazzini, E. P.; Sarwal, A. N.; Takahashi, M. Protective effect of

751

plant sterols against chemically induced colon tumors in rats. Cancer Res. 1980, 40, 403–405.

752

(25) Murillo, G.; Choi, J. K.; Pan, O.; Constantinou, A. I.; Mehta, R. G. Efficacy of garbanzo and

753

soybeans flour in suppression of aberrant crypt foci in the colons of CF-1 mice. Anticancer Res.

754

2004, 24, 3049–3055.

755

(26) Xue, Z.; Gao, J.; Zhang, Z.; Yu, W.; Wang, H.; Kou, X. Antihyperlipidemic and Antitumor

756

Effects of Chickpea Albumin Hydrolysate. Plant Foods Hum Nutr. 2012, 67, 393–400.

757

(27) Zulet, M. A.; Macarulla, M. T.; Portillo, M. P.; Noel-Suberville, C.; Higueret, P.; Martínez,

758

J. A. Lipid and glucose utilization in hypercholesterolemic rats fed a diet containing heated

759

Chickpea (Cicer aretinum L.): a potential functional food. Int J Vitam Nutr Res. 1999, 69, 403–

760

411.

761

(28) Barakat, H.; Reim, V.; Rohn, S. Stability of saponins from chickpea, soy and faba beanss in

762

vegetarian, broccoli-based bars subjected to different cooking techniques. Food Res Int. 2015,

763

76, 142–149.


Page 35 of 69


764

(29) Harini, S.; Adilaxmamma, K.; Mohan, E. M.; Srilatha, Ch.; Raj, M. A. Antihyperlipidemic

765

activity of Chickpea sprouts supplementation in ovariectomy-induced dyslipidemia in rats. J

766

Ayurveda Integr Med. 2015, 6(2), 104-10.

767

(30) Mark, K. S.; Davis, T. P. Stroke: development, prevention and treatment with peptidase

768

inhibitors. Peptides. 2000, 21(12), 1965-1973.

769

(31) Fahmy, S. R.; Soliman, A. M.; Sayed, A. A.; Marzouk, M. Possible antiosteoporotic

770

mechanism of Cicer arietinum extract in ovariectomized rats. Int J Clin Exp Pathol. 2015, 8(4),

771

3477-3490.

772

(32) Pedroche, J.; Yust, M. M.; Girón-Calle, J.; Alaiz, M.; Millán, F.; Vioque, J. Utilisation of

773

Chickpea protein isolates for production of peptides with angiotensin I-converting enzyme

774

(ACE)-inhibitory activity. Acta Pharmacol Sin. 2013, 34 (3), 380-6.

775

(33) Barbana, J. I.; Boye. Angiotensin I-converting enzyme inhibitory activity of Chickpea and

776

pea protein hydrolysates C. Food Res Int. 2010, 43, 1642–1649.

777

(34) Sreerama, Y. N.; Sashikala, V. B.; Pratape, V. M. Phenolic compounds in cowpea and horse

778

gram flours in comparison to chickpea flour: Evaluation of their antioxidant and enzyme

779

inhibitory properties associated with hyperglycemia and hypertension. Food Chem. 2012, 133(1),

780

156-162.

781

(35) Kalaiselvan, V.; Kalaivani, M.; Vijayakumar, A.; Sureshkumar, K.; Venkateskumar, K.

782

Current knowledge and future direction of research on soy isoflavones as a therapeutic agents.

783

Pharmacogn Rev. 2010, 4(8), 111-7. doi: 10.4103/0973-7847.70900.



Page 36 of 69

784

(36) Gao, Y.; Yao, Y.; Zhu, Y.; Ren, G. Isoflavone content and composition in Chickpea (Cicer

785

arietinum L.) sprouts germinated under different conditions. J. Agric. Food Chem. 2015, 63,

786

2701−2707.

787

(37) Ma H. R.; Wang, J.; Qi, H. X.; Gao, Y. H.; Pang, L. J.; Yang, Y.; Wang, Z. H.; Duan, M. J.;

788

Chen, H.; Cao, X.; Aisa, H. A. Assessment of the estrogenic activities of Chickpea (Cicer

789

arietinum L) sprout isoflavone extract in ovariectomized rats. Acta Pharmacol Sin. 2013, 34(3),

790

380-6.

791

(38) Singh, U. Antinutritional factors of Chickpea and pigeon pea and their removal by

792

processing. Plant Foods Hum Nutr. 1988, 38 (3), 251-61.

793

(39) Wati, R. K.; Theppakorn, T.; Benjakul, S.; Rawdkuen, S. Trypsin Inhibitor from 3 Legume

794

Seeds: Fractionation and Proteolytic Inhibition Study. J. Food Sci. 2010, 75 (3), C223–C228.

795

(40) Singh, U.; Jambunathan, R. Studies on desi and kabull Chickpea (Cicer arietinum L.)

796

cultivars: levels of protease inhibitors, levels of polyphenolic compounds and in vitro protein

797

digestibility. J. Food Sci. 1981, 46, 1364–1367.

798

(41) Hathcock, J. N. Residue trypsin inhibitor: Data needs for risk assessment. In Nutritional and

799

Toxicological Consequences of Food Processing, ed. M. Friedman. Plenum Press, New York,

800

USA, pp. 1991, 273-9.

801

(42) Fushiki, T.; Iwai, K. Two hypotheses on the feedback regulation of pancreatic enzyme

802

secretion. The FASEB Journal. 1989, 3 (2), 121-126.

803

(43) Roebuck, B. D. Trypsin inhibitors: potential concern for humans? J Nutr. 1987, 117(2), 398-

804

400. 36 ACS Paragon Plus Environment

Page 37 of 69


805

(44) Liener, I. E. Legume toxin in relation to protein digestibility-A Review. J. Food Sci. 1976,

806

41(5), 1076–1081.

807

(45) Frias, J.; Vidal-Valverde, C.; Sotomayor, C.; Diaz-Pollan, C.; Urbano, G. Influence of

808

processing on available carbohydrate content and antinutritional factors of CPs. Eur Food Res

809

Technol. 2000, 210 (5), pp 340-345.

810

(46) Vidal-Valverde, C.; Frías, J.; Valverde, S. Effect of processing on the soluble carbohydrate

811

content of lentils. J Food Prot. 1992, 55(4), 301-306.

812

(47) Singh, P. K.; Shrivastava, N.; Sharma, B.; Bhagyawant, S. S. Effect of Domestic Processes

813

on Chickpea Seeds for Antinutritional Contents and Their Divergence. Am. J. Food Tech. 2015,

814

3(4), 111-117.

815

(48) Francis, G.; Kerem, Z.; Makkar, H. P.; Becker, K. The biological action of saponins in

816

animal systems: a review. Br J Nutr. 2002, 88(06), 587-605.

817

(49) Singh, U. The inhibition of digestive enzymes by polyphenols of Chickpea and pigeonpea.

818

Nutr. Rep. Int. 1984, 29, 745-753.

819

(50). Kerem, Z.; German-Shashoua, H.; Yarden, O. Microwave-assisted extraction of bioactive

820

saponins from chickpea (Cicer arietinum L.) J Sci Food Agric. 2005, 85, 406–412.

821

(51) Jaffe, W. G.; Moreno, R.; Wallis, V. Amylase inhibitors in legume seeds. Nutr Rep Int.

822

1973, 7, 169-174.

823

(52) Singh, U.; Kherdekar, M. S.; Jambunathan, R. Studies on Desi and Kabuli Chickpea (Cicer

824

arietinum L.) Cultivars. The Levels of Amylase Inhibitors, Levels of Oligosaccharides and In

825

Vitro Starch Digestibility. J. Food Sci. 1982, 47(2), 510–512. 37 ACS Paragon Plus Environment


Page 38 of 69

826

(53) Mulimani, V. H.; Rudrappa G.; Supriya, D. α-Amylase inhibitors in chick pea (cicer

827

arietinum L). J Sci Food Agric. 1994, 64 (4), 413–415.

828

(54) Obiro, W. C.; Zhang, T.; Jiang, B. The nutraceutical role of the Phaseolus vulgaris α-

829

amylase inhibitor. Br J Nutr. 2008, 100(01), 1-12.

830

(55) Mulimani, V. H.; Rudrappa, G. Effect of heat treatment and germination on alpha amylase

831

inhibitor activity in chick peas (Cicer arietinum L.). Plant Foods Hum Nutr. 1994, 46(2), 133-

832

137.

833

(56) Pedroche, J.; Yust, M. M.; Lqari, H.; Megías, C.; Girón-Calle, J., Alaiz, M., Millán, F.;

834

Vioque, J. Chickpea pa2 albumin binds hemin. Plant Sci. 2005, 168 (4), 1109–1114.

835

(57) Mekbungwan, A. Application of tropical legumes for pig feed. Anim Sci. 2007, 78 (4), 342–

836

350.

837

(58) Esteban, R.; Dopico, B.; Muñoz, F. J.; Romo, S.; Labrador, E. A seedling specific

838

vegetative lectin gene is related to development in Cicer arietinum. Physiol. Plant. 2002, 114 (4),

839

619–626.

840

(59) Vioque, J.; Clemente, A.; Sánchez-Vioque, R.; Pedroche, J.; Bautista, J.; Millán, F.

841

Comparative Study of Chickpea and Pea Pa2 Albumins. J. Agric. Food Chem. 1998, 46 (9), pp

842

3609–3613.

843

(60) Sharma, U.; Katre, U. V.; Suresh, C. G. Crystal structure of a plant albumin from Cicer

844

arietinum (CP) possessing hemopexin fold and hemagglutination activity. Planta. 2014, DOI

845

10.1007/s00425-014-2236-6.


Page 39 of 69


846

(61) Bardocz, S.; Grant, G.; Pusztai, A. The effect of phytohaemagglutinin at different dietary

847

concentrations on the growth, body composition and plasma insulin of the rat. Br J Nutr. 1996,

848

76(4), 613-26.

849

(62) Liener, I. Significance for humans of biologically active factors in soybeans and other food

850

legumes. J. Am. Oil Chem. Soc. 1979, 56 (3), pp 121-129.

851

(63) Veenstra, J. M.; Duncan, A. M.; Cryne, C. N.; Deschambault, B. R.; Boye, J. I.; Benali, M.;

852

Marcotte, M.; Tosh, S. M.; Farnworth, E. R.; Wright A. J. "Effect of pulse consumption on

853

perceived flatulence and gastrointestinal function in healthy males." Food Res Int. 2010, 43(2),

854

553-559.

855

(64) Niphadkar, P. V.; Patil, S. P.; Bapat, M. M. Legumes the most important food allergen in

856

India. Allergy. 1992, 47, 318.

857

(65) Misra A.; Prasad, R.; Das, M.; Dwivedi, P. D. Prevalence of legume sensitization in patients

858

with naso-bronchial allergy. Immunopharmacol Immunotoxicol. 2008, 30(3), 529-42.

859

(66) Kulkarni, A.; Ananthanarayan, L.; Raman, K. Identification of putative and potential cross-

860

reactive CP (Cicer arietinum) allergens through an in silico approach. Comput Biol Chem. 2013,

861

47, 149-55.

862

(67) Pascual, C. Y.; Fernandez-Crespo, J.; Sanchez Pastor, S.; Ayuso, R.; Garcia Sanchez, G.;

863

Martin-Esteban, M. Allergy to lentils in Spain. Pediatr Pulmonol. 2001, 23, 41-3.

864

(68) Bar-El Dadon, S.; Pascual, C. Y.; Eshel, D.; Teper-Bamnolker, P.; Ibáñez, M. D. P.; Reifen,

865

R. Vicilin and the basic subunit of legumin are putative CP allergens. Food Chem. 2013, 138,

866

13–18. 39 ACS Paragon Plus Environment


Page 40 of 69

867

(69) Verma, A. K.; Sharma, A.; Kumar, S.; Gupta, R. K.; Kumar, D.; Gupta, K.; Giridhar, B. H.;

868

Das, M.; Dwivedi, P. D. Purification, characterization and allergenicity assessment of 26kDa

869

protein, a major allergen from Cicer arietinum. Mol Immunol. 2016, 74, 113-124.

870

(70) Herman, R. A.; Korjagin, V.

871

digestion in simulated gastric fluid. Regul Toxicol Pharmacol. 2005, 41, 175–184.

872

(71) Cuadrado, C.; Cabanillas, B.; Pedrosa, M. M,; Varela, A.; Guillamón, E.; Muzquiz, M.;

873

Crespo, J. F,; Rodriguez, J.; Burbano, C. Influence of thermal processing on IgE reactivity to

874

lentil and chickpea proteins. Mol. Nutr. Food Res. 2009, 53, 1462–1468.

875

(72) Cuadrado, C.; Cabanillas B.; Pedrosa, M. M.; Muzquiz, M.; Haddad, J.; Allaf, K.;

876

Rodriguez, J.; Crespo, J. F.; Burbano. C. Effect of Instant Controlled Pressure Drop on IgE

877

Antibody Reactivity to Peanut, Lentil, Chickpea and Soybean Proteins. Int Arch Allergy

878

Immunol. 2011, 156, 397–404.

; Schafer, B. W. Quantitative measurement of protein

(73) Gupta, R. K.; Gupta, K.; Sharma, A.; Das, M.; Ansari, I. A.; Dwivedi, P. D. Maillard reaction in food allergy: Pros and Cons. Crit Rev Food Sci Nutr, (just-accepted), 2016, DOI:10.1080/10408398.2016.1152949. (74) Vissers, Y. M.; Blanc, F.; Skov, P. S.; Johnson, P. E.; Rigby, N. M.; Przybylski-Nicaise, L.; Bernard, H.; Wal, J. M.; Ballmer-Weber, B.; Zuidmeer-Jongejan, L.; Szepfalusi, Z. Effect of heating and glycation on the allergenicity of 2S albumins (Ara h 2/6) from peanut. PLoS One, 2011, 6(8), p.e23998.


Page 41 of 69


(75) Bu, G.; Zhu, T.; Chen, F.; Zhang, N.; Liu, K.; Zhang, L.; Yang, H. Effects of saccharide on the structure and antigenicity of β-conglycinin in soybean protein isolate by glycation. Eur. Food Res. Technol. 2015, 240(2), 285-293. (76) Rupa, P.; Nakamura, S.; Katayama, S.; Mine, Y. Effects of ovalbumin glycoconjugates on alleviation of orally induced egg allergy in mice via dendritic‐cell maturation and T‐cell activation. Mol. Nutr. Food Res. 2014, 58(2), 405-417. 879

(77) Helm, R. M.; Cockrell, G.; Connaughton, C.; West, C. M.; Herman, E.; Sampson, H. A.;

880

Bannon, G. A.; Burks, A. W.; Mutational analysis of the IgE-binding epitopes of P34/Gly m Bd

881

30K. J. Allergy Clin. Immunol. 2000, 105(2), pp. 378-384.

882

(78) Marazuela, E. G.; Rodriguez, R.; Barber, D.; Villalba, M.; Batanero, E. Hypoallergenic

883

mutants of Ole e 1, the major olive pollen allergen, as candidates for allergy vaccines. Clin Exp

884

Allergy. 2007, 37(2), 251-260.

885

(79) Zuidmeer-Jongejan, L. The choice of hypoallergens for fish and peach to develop food

886

allergy specific immunotherapy (the FAST project). Clin Transl Allergy. 2011, 1, 1-1.

887

(80) Dodo, H. W.; Konan, K. N.; Chen, F. C.; Egnin, M.; Viquez, O. M. Alleviating peanut

888

allergy using genetic engineering: the silencing of the immunodominant allergen Ara h 2 leads to

889

its significant reduction and a decrease in peanut allergenicity. Plant Biotech J. 2008, 6(2),

890

pp.135-145.

891

(81) Nakamura, R.; Matsuda, T. Rice allergenic protein and molecular-genetic approach for

892

hypoallergenic rice. Biosci Biotech Biochem. 1996, 60, 1215–1221.



Page 42 of 69

893

(82) Cabanillas, B.; Pedrosa, M. M.; Rodríguez, J.; Muzquiz, M.; Maleki, S. J.; Cuadrado, C.;

894

Burbano, C.; Crespo, J. F. Influence of enzymatic hydrolysis on the allergenicity of roasted

895

peanut protein extract. Int Arch Allergy Immunol. 2012, 157(1), 41-50.

896

(83) Chicón, R.; Belloque, J.; Alonso, E.; Martín-Alvarez, P. J.; López-Fandiño, R. Hydrolysis

897

under high hydrostatic pressure as a means to reduce the binding of beta-lactoglobulin to

898

immunoglobulin E from human sera. J Food Prot. 2008, 71(7), 1453-9.

899

(84) Sung, D.; Ahn, K. M.; Lim, S. Y.; Oh, H. Allergenicity of an enzymatic hydrolysate of

900

soybean 2S protein. J Sci Food Agric. 2014, 94, 2482-2487.

901

(85) Kasera, R.; Singh, A. B.; Lavasa, S.; Prasad, K. N.; Arora, N. Enzymatic hydrolysis: a

902

method in alleviating legume allergenicity. Food Chem Toxicol. 2015, 76, 54-60.

903

(86) Clemente, A.; Vioque, J.; Sanchez-Vioque, R.; Pedroche, J.; Millán, F. Production of

904

extensive chickpea (Cicer arietinum L.) protein hydrolysates with reduced antigenic activity. J

905

Agric Food Chem. 1999, 47(9), 3776-81.

906

(87) Kalogeropoulos, N.; Chiou, A.; Ioannou, M.; Karathanos, V. T.; Hassapidou, M.;

907

Andrikopoulos, N. K. Nutritional evaluation and bioactive microconstituents (phytosterols,

908

tocopherols, polyphenols, triterpenic acids) in cooked dry legumes usually consumed in the

909

Mediterranean countries. Food Chem. 2010, 121(3), 682-90.

910

(88) Fratianni, F.; Cardinale, F.; Cozzolino, A.; Granese, T.; Albanese, D.; Di Matteo, M.;

911

Zaccardelli, M.; Coppola, R.; Nazzaro, F. Polyphenol composition and antioxidant activity of

912

different grass pea (Lathyrus sativus), lentils (Lens culinaris), and chickpea (Cicer arietinum)

913

ecotypes of the Campania region (Southern Italy). Journal of functional foods, 2014, 7, 551-557.


Page 43 of 69


914

(89) Smith, J. C.; Wilson, F. D.; Allen, P. V.; Berry, D. L. Hypertrophy and Hyperplasia of the

915

Rat Pancreas Produced by Short-term Dietary Administration of Soya-derived Protein and

916

Soybean Trypsin Inhibitor. J App Toxicol, 1989, 9(3), 175-179.

917

(90) Linde, B.; Gunnarsson, R. Influence of aprotinin on insulin absorption and subcutaneous

918

blood flow in Type 1 ( insulin-dependent ) diabetes. Diabetologia, 1985, 28, 645-648.

919

(91) Brugge, W. R.; Rosenfeld, M. S. Impairment of starch absorption by a potent amylase

920

inhibitor. Am J Gastroenterol. 1987, 82(8), 718-22.

921

(92) Puls, W.; Keup, U. Influence of an -Amylase Inhibitor (BAY d 7791) on Blood Glucose,

922

Serum Insulin and NEFA in Starch Loading Tests in Rats, Dogs and Man. Diabetologia, 1973, 9,

923

97-101.

924

(93) Kim, Y. S.; Brophy, E. J.; Nicholson, J. A. Rat intestinal brush border membrane

925

peptidases. II. Enzymatic properties, immunochemistry, and interactions with lectins of two

926

different forms of the enzyme. J Biol Chem. 1976, 251(11), 3206-12.

927

(94) Rea, R. L.; Thompson, L. U.; Jenkins, D. J. Lectins in foods and their relation to starch

928

digestibility. Nutri Res, 1985, 5(9), 919-29.

929

(95) Gee, J. M.; Wal, J. M.; Miller, K.; Atkinson, H.; Grigoriadou, F.; Wijnands, M. V.;

930

Penninks, A. M.; Wortley, G.; Johnson, I. T. Effect of saponin on the transmucosal passage of β-

931

lactoglobulin across the proximal small intestine of normal and β-lactoglobulin-sensitised rats.

932

Toxicology, 1997, 117(2), 219-28.



Page 44 of 69

933

(96) Harris WS, Dujovne CA, Windsor SL, Gerrond LL, Newton FA, Gelfand RA. Inhibiting

934

cholesterol absorption with CP-88,818 (β-tigogenin cellobioside; tiqueside): Studies in normal

935

and hyperlipidemic subjects. J Cardiovasc Pharmacol, 1997, 30(1), 55-60.

936

(97) Feeny, P. P. Inhibitory effect of oak leaf tannins on the hydrolysis of proteins by trypsin.

937

Phytochemistry, 1969, 8(11), 2119-26.

938

(98) Riedl, K. M.; Carando, S; Alessio, H. M.; McCarthy, M.; Hagerman, A. E. Antioxidant

939

activity of tannins and tannin-protein complexes: assessment in vitro and in vivo. In ACS

940

Symposium Series, 2002, 807,188-200. Washington, DC; American Chemical Society; 1999.

941

(99) Bohn, T.; Davidsson, L.; Walczyk, T.; Hurrell, R. F. Phytic acid added to white-wheat bread

942

inhibits fractional apparent magnesium absorption in humans. Am J Clin Nutr. 2004, 79(3), 418-

943

23.

944

(100) Grases, F.; Garcia-Gonzalez, R.; Torres, J. J.; Llobera, A. Effects of phytic acid on renal

945

stone formation in rats. Scand J Urol Nephrol. 1998, 32(4), 261-5.

946

(101) Marshall, J. R.; Martinez, M. E.; Albert, D. S. Wheat bran as a means of cancer

947

chemoprevention. Asia Pacific J Clin Nutr, 1999, 8, S47–S53.

948

(102) Parrish, C. C.; Pathy, D. A.; Angel, A. Dietary fish oils limit adipose tissue hypertrophy in

949

rats. Metabolism, 1990, 39(3), 217-9.

950

(103) Summers, L. K.; Fielding, B. A.; Bradshaw, H. A.; Ilic, V.; Beysen, C.; Clark, M. L.;

951

Moore, N. R.; Frayn, K. N. Substituting dietary saturated fat with polyunsaturated fat changes

952

abdominal fat distribution and improves insulin sensitivity. Diabetologia. 2002, 45, 369–377.


Page 45 of 69


953

(104) Scheppach, W.; Sommer, H.; Kirchner, T.; Paganelli, G. M.; Bartram, P.; Christl, S.;

954

Richter, F.; Dusel, G.; Kasper, H. Effect of butyrate enemas on the colonic mucosa in distal

955

ulcerative colitis. Gastroenterology, 1992, 103(1), 51-6.4.

956

(105) Manning, P. J.; Sutherland, W. H.; Walker, R. J.; Williams, S. M.; De Jong, S. A.; Ryalls,

957

A. R.; Berry, E. A. Effect of High-Dose Vitamin E on Insulin Resistance and Associated

958

Parameters in Overweight Subjects. Diabetes Care, 2004, 27(9), 2166-2171.

959

(106) Gysin, R.; Azzi, A.; Visarius, T. Gamma-tocopherol inhibits human cancer cell cycle

960

progression and cell proliferation by down-regulation of cyclins. FASEB J. 2002, 16(14), 1952-4.

961

(107) Yu, W.; Jia, L.; Park, S. K.; Li, J.; Gopalan, A.; Simmons‐Menchaca, M.; Sanders, B. G.;

962

Kline, K. Anticancer actions of natural and synthetic vitamin E forms: RRR‐α‐tocopherol blocks

963

the anticancer actions of γ‐tocopherol. Mol Nut Food Res, 2009, 53(12),1573-81.

964

(108) Kim, H. K.; Nelson-Dooley, C.; Della-Fera, M. A.; Yang, J. Y.; Zhang, W.; Duan, J.;

965

Hartzell, D. L.; Hamrick, M. W.; Baile, C. A. Genistein decreases food intake, body weight, and

966

fat pad weight and causes adipose tissue apoptosis in ovariectomized female mice. J Nutr, 2006,

967

136(2), 409-14.

968

(109) Ko, K. P.; Kim, C. S.; Ahn, Y.; Park, S. J.; Kim, Y. J.; Park, J. K.; Lim, Y. K.; Yoo, K. Y.;

969

Kim, S. S. Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in

970

Korean women but not men: results from the Korean Genome and Epidemiology Study.

971

Diabetologia, 2015, 58(4), 726-35.



Page 46 of 69

972

(110) Lian, F.; Bhuiyan, M.; Li, Y. W.; Wall, N.; Kraut, M.; Sarkar, F. H. Genistein-induced G2-

973

M arrest, p21WAF1 upregulation, and apoptosis in a non-small-cell lung cancer cell line. Nutr

974

Cancer. 1998, 31(3), 184-91.

975

(111) Banerjee, S.; Zhang, Y.; Ali, S.; Bhuiyan, M.; Wang, Z.; Chiao, P. J.; Philip, P. A.;

976

Abbruzzese, J.; Sarkar, F. H. Molecular evidence for increased antitumor activity of gemcitabine

977

by genistein in vitro and in vivo using an orthotopic model of pancreatic cancer. Cancer Res,

978

2005, 65(19), 9064-72.

979

(112) Szkudelska, K.; Nogowski, L.; Szkudelski, T. Genistein affects lipogenesis and lipolysis in

980

isolated rat adipocytes. J Steroid Biochem Mol Biol, 2000, 75(4-5), 265-71.

981

(113) Jayagopal, V.; Albertazzi, P.; Kilpatrick, E. S.; Howarth, E. M.; Jennings, P. E.; Hepburn,

982

D. A.; Atkin, S. L. Beneficial Effects of Soy Phytoestrogen Intake in Postmenopausal Women

983

With Type 2 Diabetes. Diabetes Care, 2002, 25(10), 1709-1714.

984

(114) Turktekin, M.; Konac, E.; Onen, H. I.; Alp, E.; Yilmaz, A.; Menevse, S. Evaluation of the

985

effects of the flavonoid apigenin on apoptotic pathway gene expression on the colon cancer cell

986

line (HT29). J Med Food, 2011, 14(10),1107-17.

987

(115) Liu, A. H.; Sun, X.; Wei, X. Q.; Zhang, Y. Z. Efficacy of multiple low-dose photodynamic

988

TMPYP4 therapy on cervical cancer tumour growth in nude mice. Asian Pac J Cancer Prev,

989

2013, 14(9), 5371-4.

990

(116) Han, L. K.; Sumiyoshi, M.; Zhang, J.; Liu, M. X.; Zhang, X. F.; Zheng, Y. N.; Okuda, H.;

991

Kimura, Y. Anti-obesity action of Salix matsudana leaves (Part 1). Anti-obesity action by


Page 47 of 69


992

polyphenols of Salix matsudana in high fat-diet treated rodent animals. Phytother Res, 2003,

993

17(10),1188-94.

994

(117) Gandhi, G. R.; Ignacimuthu, S.; Paulraj, M. G. Solanum torvum Swartz. fruit containing

995

phenolic compounds shows antidiabetic and antioxidant effects in streptozotocin induced

996

diabetic rats. Food Chem Toxicol. 2011, 49(11), 2725-33.

997

(118) Mallery, S. R.; Zwick, J. C.; Pei, P.; Tong, M.; Larsen, P. E.; Shumway, B. S.; Lu, B.;

998

Fields, H. W.; Mumper, R. J.; Stoner, G. D. Topical Application of a Bioadhesive Black

999

Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human

1000

Premalignant Oral Lesions. Cancer Res, 2008, 68(12), 4945-57.

1001 1002 1003 1004



Figure caption: Figure 1 Possible mechanism of blood glucose homeostasis regulated by phytolectins, phytates and amylase inhibitors that have crucial roles in diabetes management. Figure 2 The Antihypertensive potential of bioactive peptides and isoflavones with estrogenic activity presents in CP. Figure 3 Clinical complications caused by ANCs and allergens of CP. Figure 4 Possible mechanism of allergy and anaphylaxis induced by CP allergens. Figure 5 Table of Content (TOC): Graphical figure summarizing the health risk and benefits associated with chickpea consumption. 1005


Page 48 of 69

Page 49 of 69


1006 1007 1008 1009 1010 1011

1012 1013 1014 1015 1016

Table 1: Anti-obesity, anti-diabetic and anti-cancerous effects of neutraceuticals found in chick

1017

pea 49 ACS Paragon Plus Environment


S. No.

Neutraceutica

Amount

l Compound

in chick

Experimental Settings

Anti-obesity

Experimental

outcomes

Settings

Page 50 of 69

Anti-diabetic outcomes

Experimental

Anti-cancerous

Settings

Outcomes

pea 1.

Dietary fibres

17.4g/10

24 female adult Wistar

Dietary germinated

Eight

diabetic

Glucose levels of 6.3±2-4

1429 participants who

High

0g

rats were divided into

chickpea normalized

patients were given

mmol/1 after diet B were

had had one or more

intervention resulted

four

the lipid profile in

diet A (normal Italian

significantly lower than

colorectal adenoma(s)

into

Group I - Control; Group

serum

diet) for 10 days, diet

those either after diet A

3

chemoprevention.101

II

High-density

B (diet A + three to

(9.9±3.1 mmol/l) or after

identified

fourfold

increased

diet C (8.7±3.4 mmol/l).

removed were given a

groups

-

that

is,

Ovariectomized

and

liver.

mm

or

larger

lipoprotein

(HDL)

OVX

cholesterol,

body

fibres) for next 10

Daily glucose (average

high (13.5 g/day) or

uterine,

days and diet C (low

of the

low (2 g/day) placebo

spleen

carbohydrate diabetic

different times of the day)

were

diet) for another next

was

10 days.15

after diet B, and 8.2±2.3

germinated

chickpea sprouts (20% in

weight,

diet) and Group IV OVX

heart,

+ atorvastatin (1.2 mg/kg

weights

b.wt, p.o.).29

increased that were reduced

and

due

to

five values at

cancer

fibre intervention.101

3.8±2.3 3 mmol/1

mmol/1

ovariectomy.29

colon

and

(OVX) rats; Group III +

fibre

and

7.3±1.1

mmol/l, respectively, after diets A and C.15

2.

Fatty acids

62–67%

Male Wistar rats were

There

no

Seventeen subjects (6

Insulin

fed

high-fat diets

difference in body

with type II diabetes,

plasma

20%

weight between rats

6 obese and 5 obese

lipoprotein

on

containing

was


sensitivity low

and

density cholesterol

Ten patients with distal ulcerative colitis were treated for 2 weeks with sodium butyrate (100 mmol/L)

After butyrate irrigation, histological degree of inflammation decreased from 2.4

Page 51 of 69


concentrations improved

triglycerides from fish oil

of two groups but

without

or

significantly

less

were given a diet rich

with

perirenal

and

in

polyunsaturated

from

20% lard

weeks.102

triglycerides for

three

diabetes)

saturated

or

diet

rich

in fatty

epididymal fat was

polyunsaturated fatty

acids compared with the

observed in the fish

acids for two 5 weeks

diet rich in saturated fatty

oil

period.103

acids.103

fed

group

containing

LC n-3

PUFA

that

protective against

and 2 weeks with placebo in random order (single-blind trial).104

+/- 0.3 to 1.5 +/- 0.3. The endoscopic score fell from 6.5 +/- 0.4 to 3.8 +/- 0.8. On placebo, all of these parameters were 104 unchanged.

Immune incompetent Nu/Nu female BALB/c mice were injected subcutaneously with MDA-MB-231-GFP human breast cancer cells. Mice were treated with αtocopherol, γ-

γ-Tocopherol (25 µM) treated cells

has role the

accumulation

of

body fat through a lesser accumulation of fat in existing adipocytes.102 3.

Tocopherols

13.7 mg/100g

Eighty

overweight

At

3

individuals (BMI >27

plasma

kg/m2)

insulin

were

months, glucose

fasting and

concentrations

randomly allocated to

were significantly reduced

receive either 800 IU

and homeostasis model


γ-tocopherol, allracemic-αtocopherol, αtocopherol etherlinked acetic acid analog but not α-


vitamin E per day for

Page 52 of 69

assessment increased.105

3 months that was increased

to 1,200

IU per day for a further 3 months.105

4.

Carotenoids

-----------

Twelve-week-old NMRI

ATRA

The oxidative

Increased

--

male mice received one

administration

stress was evaluated

oxidation,

daily

triggered in NMRI

in 55 diabetic patients

lipid peroxidation and NO

trans

mice a reduction of

and 40 healthy

levels,

retinoic acid (ATRA) at a

body weight and of

subjects

dose of 10, 50 or 100

the

of

measuring the levels

enzymatic

mg/kg body wt during

Interscapular brown

of protein oxidation,

nonenzymatic

the 4 days.107

adipose

lipid

antioxidants and playing a

injection

subcutaneous of

all

mass

tissue,

by


protein

decreases

the

levels of and

tocopherol, allracemic-α-tocopherol, α-tocopherol etherlinked acetic acid analog and α tocopherol + γ tocopherol.107

tocopherol and α tocopherol + γ tocopherol significantly inhibited tumor burden of human MDA-MB231 cells in nude mice. Immunohistochemica l analyses of tumor tissue showed that all-rac-αT and α-TEA increased apoptosis and decreased proliferation in tumor cells while γT was associated with increased tumor cell apoptosis only.

Page 53 of 69


epididymal

white

peroxidation

and

major role in diabetic

adipose tissue and

some enzymatic and

complications.

inguinal

white

nonenzymatic

β-carotene

adipose

tissue

carotene,

depots.107

(βretino)

antioxidants.108

(µmol/l)-

healthy-

3.86±0.34,

diabetic

individual-

2.23±0.4,

Retinol

(µmol/l)-

healthy-

3.24±0.65, diabetic- 1.75±0.52.108 5.

Isoflavanoids

-----------

Ovariectomized

693 individuals with

In women, a decreasing

--

mice (9 mo old) were

mg/kg)

type 2 diabetes and

trend in the risk of type 2

given 0, 150, or 1500

food intake (FI) by

698

diabetes

mg/kg genistein for 3

14%

included

weeks. (PM),

female

Parametrial inguinal (ING),

Genistein

(1500 reduced

controls

study.

was demonstrated with

weight (BW) by 9%.

Isoflavone biological

categories of increasing

PM

ING

markers

genistein

were

daidzein,

There was no association

and

and

body

in

were

(genistein,

concentration.

and retroperitoneal (RP)

weights

fat pads were weighed

decreased 22% and

glycitein and equol)

between the risk of type 2

and assayed for apoptosis

19%

were

diabetes and the plasma

(%

Apoptosis in ING

plasma to examine

concentration of daidzein

fat

whether

and glycitein. In men, the

fragmentation.109

DNA

respectively.

was increased

measured

in

isoflavones


The pancreas of anaesthetized female nude mice was exposed to pancreatic cancer cells COLO 357 and L3.6pl. Mice were divided into four groups: (a) untreated control; (b) only gemcitabine (80 mg/kg body weight), once every other day (i.v. injection); (c) genistein, everyday orally for 10 days; and (d) genistein and 111 gemcitabine.

Treatment with either genistein or gemcitabine alone in mice harboring COLO 357 cells caused 13% and 27% reduction in tumor weight, respectively. combination of genistein and gemcitabine treatment showed significant decrease (75%) in tumor weight compared with untreated 111 control.


290%.109

Page 54 of 69

are associated with

concentrations of the four

the development of

isoflavones

type

glycitein,

2

diabetes

genistein, daidzein

showed

and

according to

equol

no

sex.110

association with risk of type 2 diabetes.110

6

Phytoestrogens

Genistein (0.01, 0.3,

A

incubated with genistein

0.6

postmenopausal

(0.01, 0.3, 0.6 and 1

clearly restricted (1

women

mM). [14C]acetate was

nM)

controlled

used as the substrate for

glucose conversion

lipogenesis.112

-----------

Rat

-------

adipocytes

were

total

of

32

of

N u d e BAL B / c m

Compared

phytoestrogen

icewere use d f

control, formononetin

supplementation

or

suppressed tumor

demonstrated

subcutaneous

growth. High dose of

diabetes were given

significantly lower mean

implantation of human

formononetin showed

to total lipids in the

phytoestrogens

(soy

values for fasting insulin

cervical

cell

much more inhibiting

absence

protein

g/day,

(mean ± SD 8.09±21.9%)

HeLa. When tumors

and

reached about 5 mm in

effect of tumor growth than low dose.115

and

1

mM)

[U-14C]

and

with

12

placebo, diet-

type

30

After

2

weeks

insulin

resistance

tumor

presence of insulin.

isoflavones

The anti-lipogenetic

mg/day)

action of genistein

placebo (cellulose 30

the mice were divided

may be an effect not

g/day) for 12 weeks.

into three groups (n

only of alteration in

114

=8) and were

glucose

132 versus

transport

and metabolism, but


(6.47± 27.7%).114

diameter,

administered per os with different doses of formononetin.115

with

Page 55 of 69


this

phytoestrogen

can also restrict the fatty acids synthesis and/or

their

esterification.112 7.

Phenolic

-----------

Polyphenols were given

Body weights at 2-9

Phenolic

compounds

-------

to female mice at a dose

weeks and the final

containing

rutin

concentrations 200 and

oral lesions and 10

improvement

of 570 mg/kg for 9

parametrial adipose

(1.36% w/w), caffeic

400 mg/kg reduced blood

healthy

seen in seven

weeks. 116

tissue weights were

acid (12.03% w/w),

glucose level by 17.04%

were asked to apply

patients’

significantly

gallic

and 42.10%,

freeze-dried

disease

lower

acid

extract

(4.78%

Phenolic

extract

at

Twenty

individuals

individuals

black

Histopathologic was

lesions, progression

in mice fed the high-

w/w) and

respectively in diabetic

raspberry

(increase) in grade in

fat diet with 5%

catechin (0.46% w/w)

rats.

Gel (0.5 g applied four

four

polyphenols.116

of S. torvum fruit was

Immunohistochemical

times

6

patients,

administered orally at

observation of islets in

weeks for a total 84g

patients’

a dose of 200 and 400

extract

applied over the study

exhibited no change

mg/kg/day

rats showed apparent β-

duration). 118

(stable

to

streptozotocin

treated

diabetic

cells regeneration.117

daily

for

and

disease)

induced diabetic rats

microscopic

for 30 days.117

appearance.118


nine lesions

in


Page 56 of 69

Table 2 (A). Phenolic contents in native chickpeas (µg/g) Sl. No.

Compound

Hithamani et al.,13 (µg/g)

Kalogeropoulos et al.,87 (µg/100g)

Fratianni et al.,88 Castelcivita Ecotype

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Gallic acid Protocatechuic acid p-hydroxy benzoic acid Gentisic acid Vanillic acid Syringic acid p-coumaric acid Ferulic acid Sinapic acid Salicylic acid Luteolin t-cinnamic acid Caffeic acid Chlorogenic acid p-Hydroxyphenylacetic acid

40.2 358.9 10.5 26.0 80.8 222.1 n.d. 0.90 7.81 n.d. 1.56 n.d. NA NA NA

n.d. n.d. 27.5 NA 56.9 n.d. 90.4 125.7 115.7 NA NA 35.3 128.7 87.9 n.d.

6,20 NA NA NA NA NA 0,43 5,03 NA NA 0,55 NA 0 4,62 NA

16. 17. 18. 19. 20. 21. 22. 23. 24.

Phloretic acid Catechin Chrysin Epicatechin Genistein Kaempferol Quercetin Resveratrol Rutin

NA NA NA NA NA NA NA NA NA

n.d. 152.7 169.7 88.3 91.7 n.d. n.d. 117.1 NA

NA 178,21 NA 1,23 NA NA 3,17 NA 0


(µg/g)

Sassano Ecotype 5,42 NA NA NA NA NA 0 8,37 NA NA 0 NA 0 7,37 NA

NA 147,49 NA 1,36 NA NA 0,37 NA 0

Page 57 of 69


Table 2 (B). Impact of domestic processing on phenolic components of chickpea % influence during these conditions Sl. No. compound native(µg/g) 1. Gallic acid 40.2 2. Protocatechuic acid 358.9 3. p-hydroxy benzoic acid 10.5 4. Gentisic acid 26.0 5. Vanillic acid 80.8 6. Syringic acid 222.1 7. p-coumaric acid n.d. 8. Ferulic acid 0.90 9. Sinapic acid 7.81 10. Salicylic acid n.d. 11. Luteolin 1.56 12. t-cinnamic acid n.d. Total identified 748.8 phenolic compound

sprouting roasting -63.4 n.d. -93.6 +43.2 -6.2 +41.9 -41.9 +32.3 -8.1 -13.1 -6.9 -186.9 n.d. n.d. n.d. n.d. 0 n.d. +29.2 (fold) n.d. n.d. n.d. n.d. n.d. -50.2 +9.5

pressure-cooking -68.6 +30.0 n.d. -47.6 -90.6 -15.8 +0.33 (fold) +7.7 -0.47 +76.6 (fold) +4.1 (fold) n.d. +7.8

open-pan boiling -60.9 -20.8 +448.5 -41.5 -57.4 +21.6 +0.51 (fold) -6.6 -93.9 +37.5 (fold) +5.3 (fold) n.d. -3.2

microwave heating -48.2 -13.0 +407.6 -28.8 -44.1 +59.7 +0.46 (fold) -6.6 -93.7 +6.57 (fold) +6.5 (fold) +2.93 (fold) +10.2

n.d. : not detectable; +sign : increase; - sign : decrease; Hithamani et al.,13

Table 2 (C). Impact of domestic processing on bioaccessible phenolic compounds of chickpea % influence during these conditions Sl. no.

compound

native(µg/g)

sprouting

roasting

pressure-cooking


open-pan boiling

microwave heating


1. Gallic acid 78.5 +4.3 2. Protocatechuic acid 45.7 +10.0 3. Salicylic acid 322.6 +63.3 4. Rutin 29.8 -54.6 5. t-cinnamic acid n.d. n.d. Total identified 476.6 -44.6 phenolic compound (µg/g) +sign : increase; - sign : decrease; Hithamani et al.,13

+13.2 +4 (fold) -27.2 +1.6 +153 (fold) +45.5

-29.5 +4.1 (fold) 0 +7.7 n.d. +25.3

1018


Page 58 of 69

+0.8 +62.1 -13.8 +34.5 n.d. -1.1

+27.6 +3.7 (fold) -0.5 +9.3 n.d. +30.6

Page 59 of 69


1019

Table 3. Impact of domestic processing on total Polyphenols and Flavonoids content and their bioaccessibility in

1020

chickpea Native

Sprouting

Roasting

1.54

1.86

1.75

1.49

1.62

1.75

+8.72

1.47 0.10

pressure cooking

Open pan boiling

Microwave heating

1021 TPC (mg/g)

a

bioaccessible TPC (mg/g)

1022

% bioaccessibility

1023

TFC (mg/g)

1024

bioaccessible TFC (mg/g)

1025

% bioaccessibility

a

_

b

b

_

2.36

2.53

3.43

1.33

1.35

1.40

+17.44

-10.72

-9.39

-6.04

1.75

1.43

0.29

0.24

0.33

0.13

0.10

0.11

0.10

0.09

0

+10

+30

+sign : increase; - sign : decrease; aGallic acid equivalents,

b

0

-10

Catechin equivalents; TPC: total phenolic content: TFC : total

flavonoids content : Hithamani et al.,13



1026

Page 60 of 69

Table 4. Toxic components of raw chickpea

Toxic compounds

Anti-nutritive

References 1027

Amount

Unit

Trypsin inhibitor activity

8.29-11.90

mg protein/dm

31, 37

Amylase inhibitor

11.6-81.4

g protein/dm

52

Phytic acid

1.21-10.6

g/kg

31, 37

Polyphenol

3.39

-

31

Saponin

0.91

mg/g

31

Tanin

4.85

mg/g

31

Raffinose

0.62-1.45

g/100g dm

31

Ciceritol

2.51-2.78

-

Stachyose

0.74-2.56

-

Verbascose

0-0.19

-

Compounds (ANCs)

Oligosaccharides


1028

Page 61 of 69


Table 5. Deleterious and beneficial effects of anti-nutrient compounds found in chick pea S.

Anti Nutrient

No.

Compound

1.


different

doses

of

Deleterious health outcomes

trypsin


Beneficial health outcomes

Dose dependent increase in relative Ten Type I diabetic patients with normal

Four

Inhibitors

inhibitor i.e. 0, 0.3, 0.6 and 1.2% in

pancreatic weight, cell volume, nuclear insulin requirement were given

I

well as plasma free insulin was

diet were given to mice on day 2 and

density as well as mitotic index was labelled soluble insulin (10U) together

higher in protease inhibitor

7.89

observed.89

with protease inhibitor (100000 KIU) or

group as compared to diluents

its

group.90

diluent

on

two

125

consecutive

The absorption rate of

125

Trypsin

I as

mornings.90 2.

Amylase

Thirteen

Inhibitors

individuals

were

given

Over the 8-h observation period, 4.7

Seven healthy male volunteers were

15 minutes after administration

lactulose 20 g, spaghetti alone, and

+/-

was

administered with 100 g of starch in 175

blood

spaghetti with amylase inhibitor (3.8

malabsorbed and 7.0 +/- 1.4% of the

ml/person that also contain α-amylase

significantly reduced and the

g). Samples of breath were collected

spaghetti with amylase inhibitor was

inhibitor (350 mg and 700 mg).92

serum

(at frequent intervals) for 2 h after the

malabsorbed. It was also found that

lactulose and for 8 h after the

amylase inhibitor at a concentration of

spaghetti meal and analyzed for

more than 5 mg/ml decreased the

hydrogen concentration.91

amylase activity by more than 96% in

1.9%

of

the

spaghetti

glucose

insulin

levels

level

were

was

increased after 30 and 45 min.92

duodenal juice.91 3.

Phytolectins

Two

rat

intestinal

brush

border

Line of precipitation was observed


Different

foods

containing

lectins

Out of these foods, chick pea


Page 62 of 69

membrane peptidases were assayed

with

when

(wholemeal bread, white bread, white

and red kidney bean lectins

for their interaction with various sugar

diffused against the two peptidases on

rice, corn flakes soybean, black eyed

(180 HU/mg and 360 HU/mg)

specific lectins.93

immunodiffusion plates. No precipitin

beans, chick pea, red kidney bean etc)

had the capability to lower the

line was formed with concanavalin A,

were tested for their capability of

blood glucose due to their

wheat germ agglutinin and ricin.93

lowering glycemic index in normal and

binding of carbohydrates and

diabetic persons.94

thereby lowering the glycemic

phytoheamagglutinin

index.94 4.

Saponins

Twenty male Brown Norway rats

histological examination of tissue

Tiqueside, a synthetic saponin was given

Tiqueside produced a dose-

were exposed to β-lactoglobulin or

samples

in 3 different doses (1, 2 and 3 gm/day)

dependent reduction in plasma

saponin or a combination of both.95

exposed to saponin

to 15 hypercholesteromic outpatients

LDL cholesterol levels in the

revealed signs of epithelial damage,

(low-density lipo protein cholesterol >

hypercholesteromic patients.96

infiltration of

160 mg/dl) for three 2 weeks treatment

eosinophils and slight to moderate

periods, each separated by a 3-week

villus atrophy.

placebo period.96

from intestinal

Damaged

segments

epithelial

cells were most evident

at

villus

tips

in

nonsensitised animals, where

the

mucosa

had

been

exposed to saponin before addition of β-lactoglobulin.95


Page 63 of 69

5.


Tannins

solutions

It was found that the water-soluble

Young rats were maintained for 6.5

Oxidative stress in different

(containing 10, 20 or 30 mg) were

fraction of tannin has the ability to

weeks on diets of rat chow and either

organs of rats that received

brought to 20”. Casein in aqueous

bind casein

water or green tea containing tannins ad

green tea (containing tannins)

solution (18.9 mg in 4 ml) was

complex.97

lib.98

was reduced in comparison of

5

ml

of

the

tannin

in

the

form

of

a

mice that received water.98

added to each, followed by 3 ml of 0.1 M sodium citrate buffer of pH 5.0. After 2 or 15 hr, samples were centrifuged (3000 revjmin, 5 min). The sedimented complexes

were

washed

with

buffer, rinsed briefly with water to remove buffer, and dried at 85 0C. 97

6.

Phytic acid

8-9 healthy adults were given 200 g

The addition of phytic acid lowered

Male rats were divided into four groups

In the rats treated with the

phytic acid-free wheat bread on days

fractional

magnesium

of 15, 10, 10 and 12 rats each. The rats

aqueous phytic acid and phytic

1 and 3. Phytic acid was added in

absorption from 32.5 +/- 6.9% (no

of Group I were treated with ethylene

acid/zinc mixture, the number

whole-meal (1.49 mmol) and in

added phytic acid) to 13.0 +/- 6.9%

glycol; of Group II with ethylene glycol

of

brown bread (0.75 mmol). Each test

(1.49 mmol added phytic acid; P

Health Risks and Benefits of Chickpea (Cicer arietinum) Consumption

Recommend Documents