Chemical Education Today
Research Advances: Improving Our Understanding of Health Benefits and Dangers Associated with Nature's Chemical Cupboard by Angela G. King Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, United States
[email protected].
The Secret behind the Cone Snail's Venom Pump Scientists have discovered the secret of how an amazing sea snail injects its venom after shooting a harpoon-like tooth into its prey, or some unlucky swimmer, at jetliner speeds (1). The creatures, called cone snails, use a highly specialized structure that instantly pumps the paralyzing venom through the tooth and into its target. Helena Safavi-Hemami, Anthony Purcell, and colleagues note that cone snails live mainly in the shallows of the world's tropical oceans. Prized by seashell collectors for their beautiful shells, the snails are up to nine inches long. Their mouths have a blow-gun-like structure that shoots a barbed, dart-like “tooth” at about 400 mph. The tooth injects venom into fish, worms, or other prey. The snails occasionally sting swimmers, causing pain and sometimes death. They can reload the shooter with additional harpoons. The venom is produced in the venom duct, a long tube attached to the harpoon on one end and to the venom bulb in the snail's mouth (Figure 1). The scientists used a combination of proteomics, molecular biology, and morphological examination to study the role of the venom bulb in venom delivery and translocation. Analysis of proteins in venom bulbs found high concentrations of arginine kinase, a protein that enables squid and scallops to swim away from danger with extreme speed. Its abundance in the bulb suggests that arginine kinase enables the venom bulb to undergo rapid, repeated contractions to quickly force the venom through the venom duct to the harpoon and into the prey, the scientists say. These researchers also identified specialized muscles in the venom bulb that appear to aid in this process. More information on Purcell's research is available online (2). Educators interested in this research may want to use a published experiment in which students analyze snake venom by electrophoresis (3), or incorporate the chemistry of bee stings into their lecture (4). Research Advances has previously reported on a new method for identifying compounds in spider venom without the isolation of individual compounds (5). Concerns about the Safety of Certain “Healthful” PlantBased Antioxidants Scientists are calling for more research on the possibility that some supposedly healthful phytoantioxidants (PAO), including those renowned for their apparent ability to prevent cancer, may actually aggravate or even cause cancer in some individuals. Their
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Figure 1. Venom apparatus of cone snails. (A) Cartoon depicting a cone snail hunting a marine worm. (B) Schematic of the cone snail venom apparatus. The venom is synthesized in the tubular venom gland and translocated into the proboscis prior to injection. The venom bulb is located at the distal end of the venom gland. Harpoon-like radular teeth are synthesized in the radular sac and are moved into the proboscis and propelled into the prey by a high-speed hydraulic mechanism. Venom is then injected into the prey through the hollow radular tooth. (C) Crosssection through the venom bulb of Conus novaehollandiae stained to differentiate muscle (red) from collagen (blue); scale bar: 50 μm. The complementary schematic representation of the venom bulb depicts the orientation of the collagen sheet and fibers (white). (D) Longitudinal section through the venom bulb; scale bar: 50 μm. (E) Magnification of the cross-section through the bulb. The radial (dashed line), circular (light blue area), and longitudinal (white circles) muscle fibers are depicted. (F) Comparison of the epithelial layers of the venom bulb (Fi and Fii) and venom gland (Fiii and Fiv). Venom granules that fill the lumen and the secretory cells of the venom gland (purple and yellow ovoid shapes in Fiii and Fiv) are absent from the bulb. The circular (light blue area) and radial (dashed line) muscle fibers of the bulb are depicted. Reprinted with permission from ref 1. Copyright 2010 American Chemical Society.
recommendation for caution follows a study in which the two antioxidants quercetin and ferulic acid (Figure 2, 1 and 2)
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r 2011 American Chemical Society and Division of Chemical Education, Inc. pubs.acs.org/jchemeduc Vol. 88 No. 3 March 2011 10.1021/ed1011426 Published on Web 01/11/2011
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appeared to aggravate kidney cancer in severely diabetic laboratory rats (6). Kuan-Chou Chen, Robert Peng, and colleagues note that vegetables, fruits, and other plant-based foods are rich in antioxidants that appear to fight cancer, diabetes, heart disease, and other disorders. Among those antioxidants is quercetin, especially abundant in onions and black tea, and ferulic acid, found in corn, tomatoes, and rice bran. Both are also ingredients in certain herbal remedies and dietary supplements. But questions remain about the safety and effectiveness of some antioxidants, with research suggesting that quercetin could contribute to the development of cancer, the scientists note. The team of researchers found that diabetic laboratory rats fed either quercetin or ferulic acid developed more advanced forms of kidney cancer, and concluded the two antioxidants appear to aggravate or possibly cause kidney cancer (Figure 3). “Some researchers believe that quercetin should not be used by healthy people for prevention until it can be shown that quercetin does not itself cause cancer”, the report states. “In this study we report that quercetin aggravated, at least, if not directly caused, kidney cancer in rats”, the authors of the report add, suggesting that health agencies like the U.S. Food and Drug Administration should reevaluate the safety of plant-based antioxidants. While tumorigenicity of ferulic acid is unclear, for quercetin the scientists attribute it to the prooxidant effect, the insulinsecretagogue bioactivity, and competitive and noncompetitive inhibition of O-methyltransferase (6).
Figure 2. Structure of antioxidants quercetin (1) and ferulic acid (2). Structures provided by A. King.
Quercetin is a model flavonoid and published teaching labs use its inherent fluorescence to determine the binding constant for a protein-flavonoid interaction (7). This Journal has also published an undergraduate experiment in which flavonoids in wine are quantified using high performance liquid chromatography (8). Black Rice versus Inflammation Scientists are reporting evidence that black rice, a variety of the grain that is the staple food for one-third of the world's population yet little-known in the West, may help soothe the inflammation involved in allergies, asthma, and other diseases (9). Black rice contains bioactive anthocyanin pigments, while the more common brown rice contains caffeic, ferulic, and gallic acids among other simple phenols (10), and Mendel Friedman and colleagues point out that their previous research showed several potential health benefits of eating black rice bran. Those experiments, which were done in cell cultures, hinted that black rice bran suppressed the release of histamine, which causes inflammation. Bran is the outer husk of the grain, which is removed during the processing of brown rice to produce the familiar white rice. In the new study, researchers tested the effects of black rice bran extract on skin inflammation in laboratory mice. When they injected the extract into the mice, it reduced skin inflammation by about 32% compared to control animals, and also decreased production of certain biomarkers known to promote inflammation. Brown rice bran extract did not have these effects, the researchers say. When the scientists fed the mice a diet containing 10% black rice bran, it reduced swelling associated with allergic contact dermatitis, a common type of skin irritation (Figure 4). The findings “further demonstrate the potential value of black rice bran as an anti-inflammatory and anti-allergic food ingredient and possibly also as a therapeutic agent for the treatment and prevention of diseases associated with chronic inflammation”, the article notes.
Figure 3. Photographs of kidneys. Rat groups c, e, g, and h apparently show nodular tumors on the renal cortical layer. The control group had kidneys normal in size and texture (a). The other groups apparently show renal cell tumors in groups: b, diabetic; c, glibenclamide (600 μg/kg); d, gallic acid; e, rutin; f, EGCG; g, ferulic acid; and h, quercetin; or g, adenocarcinoma in ferulic acid; and h, quercetin. All phytoantioxidants were incorporated at 70 mg/kg of diet. The experimental period was 28 weeks. Reprinted with permission from ref 6. Copyright 2010 American Chemical Society.
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action mechanism and the identities of individual compounds in the extract that initiate the biological response. Anthocyanins are a colorful way to introduce students to chemical concepts, and published experiments include activities involving pH, hydrolysis, sulfite quantification in wine, and chromatographic separation of anthocyanins (11-14). Anthocyanin chemistry can be integrated into topics ranging from autumn leaf changes (15) to recent advances in solar power (16, 17). Friedman has also led research on antimicrobial compounds found in food extracts. A description of this research reports on how this work may lead to food wrap that fights pathogens that may cause food-borne illness (18). Literature Cited
Figure 4. Changes in thickening or swelling of ear skins of mice. (A) Effect of treatment of rice bran extracts by intraperitoneal injection on TPAinduced ear thickening or swelling at various time points. The intraperitoneal treatment of vehicle (DMSO) alone (striped bar), brown rice bran extract (open bar), and black rice bran extract (closed bar) was performed for 14 days followed by topical application of TPA. Data are expressed as mean, SD (n = 10). (B) Effect of the treatment of rice bran extracts by intraperitoneal injection on histological changes in stained TPA-induced ear tissues. Panel 1, normal skin; Panel 2, intraperitoneal injection with vehicle alone prior to topical application of TPA; Panel 3, intraperitoneal injection with brown rice bran extract prior to topical application of TPA; Panel 4, intraperitoneal injection with black rice bran extract prior to topical application of TPA. The symbols * and ** in panel A denote data statistically different from the group subjected to intraperitoneal injection with vehicle alone at p < 0.05 and p < 0.01, respectively. Reprinted with permission from ref 9. Copyright 2010 American Chemical Society.
Friedman's team determined that the black rice extract elicited marked changes in the expression of six genes, but researchers will have to do further work to determine the molecular
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1. Safavi-Hemami, H.; Young, N.; Williamson, N.; Purcell, A. Proteomic Interrogation of Venom Delivery in Marine Cone Snails: Novel Insights into the Role of the Venom Bulb. J. Proteome Research 2010, 9, 5610–5619. 2. University of Melbourne Web Page for Tony Purcell. http://www. biochemistry.unimelb.edu.au/research/res_purcell.html (accessed Dec 2010). 3. Evans, C.; Torre, F. J. Chem. Educ. 1988, 65, 101–1012. 4. O'Connor, R.; Peck, L. J. Chem. Educ. 1980, 57, 206–209. 5. King, A. J. Chem. Educ. 2005, 82, 10–14. 6. Hsieh, C.-L.; Peng, C.; Cheng, Y.-M.; Lin, L.-Y.; Ker, Y.-B.; Chang, C.-H.; Chen, K.-C.; Peng, R. Quercetin and Ferulic Acid Aggravate Renal Carcinoma in Long-Term Diabetic Victims. J. Agric. Food Chem. 2010, 58, 9273–9280. 7. Ingersoll, C.; Strollo, C. J. Chem. Educ. 2007, 84, 1313–1315. 8. da Queija, C.; Queiros, M.; Rodrigues, L. J. Chem. Educ. 2001, 78, 236–237. 9. Choi, S.; Kim, S.; Kang, M.; Nam, S.; Friedman, M. Protective Effects of Black Rice Bran against Chemically Induced Inflammation of Mouse Skin. J. Agric. Food Chem. 2010, 58, 10007–10015. 10. Zhang, M.; Zhang, R.; Zhang, F.; Liu, R. Phenolic Profiles and Antioxidant Activity of Black Rice Bran of Different Commercially Available Varieties. J. Agric. Food Chem. 2010, 58, 7580–7587. 11. Markwell, J.; Curtright, R.; Rynearson, J. J. Chem. Educ. 1996, 73, 306–309. 12. Curtright, R.; Emry, R.; Markwell, J. J. Chem. Educ. 1999, 76, 249–254. 13. Soares, M.; Ramos, L.; Cavalheiro, E. J. Chem. Educ. 2002, 79, 1111–1113. 14. Curtright, R.; Rynearson, J.; Markwell, J. J. Chem. Educ. 1994, 71, 682–684. 15. Alkema, J.; Seager, S. J. Chem. Educ. 1982, 59, 183–186. 16. Smestad, G.; Gratzel, M. J. Chem. Educ. 1998, 75, 752–756. 17. Smestad, G. J. Chem. Educ. 1998, 75, 1203. 18. Spices and Herbs Web Page of the McCormick Science Institute. http://www.mccormickscienceinstitute.com/content.cfm? ID=10503 (accessed Dec 2010).
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