The Effects of Morinda citrifolia L. Noni on High Blood

Chapter 39

Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: September 19, 2008 | doi: 10.1021/bk-2008-0993.ch039

The Effects of Morinda citrifolia L . Noni on High Blood Pressure: A Mechanistic Investigation and Case Study 1

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'Afa Kehaati Palu Raevonne A. Santiago , Brett J. West , Norman Kaluhiokalani , and Jarakae Jensen 2

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Noni Benefits Research, Tahitian Noni International, American Fork, UT 84003 Exercise and Sports Science Department, Brigham Young University of Hawaii, Laie, HI 96762

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Morinda citrifolia L. noni has been used in Polynesia for over 2,000 years. During that time, it has accumulated a myriad of reputed health benefits. Traditional healers have used different parts of the Noni tree to treat pain, inflammation, diabetes, gout, wounds, cancer, high blood pressure, and numerous other ailments. Most of the reputed benefits have been limited to published reports in the non-scientific literature. However, with the recent introduction and marketing of noni-based beverages and products, there is increased interest among members of the scientific community to better understand its basic chemistry and potential health benefits. The number of people reported to have successfully lowered their high blood pressure from drinking Noni fruit juice and TAHITIAN NONI® Juice has grown dramatically, but its mechanisms of action are largely unknown. Our focus is to elucidate the possible mechanisms involved in vitro, and to report a study on medicinally diagnosed high blood-pressure individuals,

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© 2008 American Chemical Society In Functional Food and Health; Shibamoto, T., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2008.

447 who were administered noni juice, while not taking prescribed blood-pressure medications. In vitro, TAHITIAN NONI® Juice (TNJ) in concentrations of 1 and 5% inhibited angiotensin converting enzymes (ACE) by 105 and 113%, respectively. TNJ also showed an IC of 1.6 and 4.3% of the AT1 and A T receptors, respectively. Noni fruit juice concentrate (NFJC) showed an IC50 of the AT1 and A T receptors of 1.97 and 2.29%, respectively. The test group consisted of 10 subjects (7 males, 3 females, ages 28-56 years) who were medically diagnosed with high blood pressure, but currently not taking any prescribed medications. Each subject consumed 2 ounces of TNJ twice a day, for 1 month. The group had average pre-test and post-test blood pressure of 144/83 and 132/76, respectively. The preliminary results suggest that NFJC and TNJ are able to lower high blood pressure by inhibiting ACE enzymes and AT receptors. The mechanisms elucidated warrant further clinical trials to assess the efficacy and dosage of TNJ on medically diagnosed high blood pressure patients. 50

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The ancestors of Polynesia are believed to have brought with them many plants, commonly known as canoe plants, as they migrated from Southeast Asia some 2000 years ago (7, 2). Though the exact number of canoe plants, brought, is still debated, it is estimated to be about 20-30 plants. Among the plants was Morinda citrifolia L., commonly known as noni. The popularity of the noni plant was likely due to traditional and medicinal usages. Traditional non-medicinal usage of noni includes, but is not limited to, canoe building and dyeing of traditional clothes made from the hiapo tree (Broussonetia papyrifera). The medicinal usages of the noni tree are purported by healers to include a repertoire of health benefits: antibacterial, antiviral, antifungal, kanisa (anticancer), antihelminth, mamahVia (analgesic), pupula (anti-inflammatory), fakamalohi sino (immune enhancing), hangatamaki (boils), lavea (cuts), mamulu (bruises), langa e hokotanga hui (anti-gout), suka (anti-diabetes), langa kete (stomachache), lafa (ring worms), mata kovi (styies) and toto ma'olunga (antihypertension) and others (2, 3). However, much of the scientific evidence to support these traditional claims has been lacking. The advent of Tahitian Noni International in 1996 has sparked numerous scientific research efforts that are now being reported ir\ professional scientific meetings and in peer-reviewed scientific journals. The anti-hypertension effects NFJC and TNJ were investigated to: (1) elucidate the possible mechanisms involved and (2) assess its efficacy and

In Functional Food and Health; Shibamoto, T., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2008.

448 possible dosage necessary to lower high blood pressure in medically-diagnosed high blood pressure patients.


Materials and Methods The NFJC and TNJ for this study were obtained from Tahitian Noni International. The subjects (28-56 years old) were all diagnosed by their primary-care physician to have high blood pressure, did not take prescription drugs, and were volunteer participants. Only those with an average systolic pressure > 130 and at least 1 diastolic pressure > 80 were included in this study. All blood pressure readings (pre-test and post-test) were done using an automatic cuff heart rate and blood-pressure monitor, and under supervision of a licensed physician.

Angiotensin Converting Enzyme Assay Test materials NFJC and TNJ in concentrations of 1, 5, and 10% each, were dissolved in 1% DMSO and incubated with ACE enzymes (Sigma, Milwaukee, WI), together with 500 pM (N-3-[2-furyl]acryloyl)-Phe-Gly-Gly (FAPGG) substrate. The reaction mixtures were incubated in a buffer (50 mM HEPES, 300 mM NaCl, and pH 7.5) at 25 °C for 30 minutes. The FAPGG was quantified spectrophotometrically according to established protocol (5) and compared to the reference compound Captopril.

Angiotensin Receptor Assay Angiotensin ATj\ Both NFJC and TNJ in concentrations of 1, 5, and 10%, were dissolved in 1% DMSO and incubated in a buffer (50 mM Tris-HCl, pH 7.4, 5 mM MgCl , 0.1% BSA, and 1 mM EDTA) and 0.05 nM [ I] (Sar , Ile )Angiotensin II ligand from human recombinant CHO (Chinese Hamster Ovary) cells for 60 minutes at 37 °C. A non-specific ligand containing 10 pM Angiotensin II was also used in each of the reaction mixtures. The radioligand binding was quantified and compared to the reference compound Saralasin according to the established protocol for ATi assay (4). Angiotensin AT : NFJC and TNJ concentrations for the AT2 assays were prepared as above. They were then incubated with 0.025 nM [ I] CGP42112A ligand from human recombinant Hela cells in an incubation buffer as described above for the AT . A non-specific ligand (as described above) was used according to the established protocol for A T assay (5,6). 125

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449 TAHITIAN NONI® Juice Effects on High Blood Pressure Patients Ten hypertensive patients (7 males and 3 females) were involved in this study. Blood pressure readings were collected from the patients, three different times during the pre-test phase. Two ounces of TNJ were administered, twice daily, before breakfast and dinner, during the 4-week test. At the end of the study, triple blood pressure readings were taken of each patient for comparison with the pre-test readings.


Results Angiotensin Converting Enzyme Inhibitory Effects of Noni NFJC concentrations of 1 and 5% inhibited ACE enzymes by 105 and 113%, respectively (Figure 1).

Figure 1. The inhibitory effects ofNFJC in 1 and 5% concentrations on angiotensin converting enzymes (ACE).

TNJ concentrations of 1, 5, and 10% inhibited ACE enzymes by 52, 78, and 105%, respectively (Figure 2).



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Figure 2. The inhibitory effects of TNJ in 1, 5, and 10% concentrations on ACE enzymes.

Angiotensin Receptor Effects of Noni Table I shows that both NFJC and TNJ bind significantly to angiotensin receptors AT! and A T at concentrations of 5% and 10%. 2

Table I. The Binding and Inhibitory Effects of Three Different Concen trations of NFJC and TNJ on Angiotensin Receptors A T i and A T . 2

Noni Samples NFJC

TNJ

Concentration, % 1 5 10 1 5 10

AT, 44 102 101 12 99 100

AT 7 102 102 5 62 77 2

High Blood Pressure Patients Pre-Test and Post-Test The blood pressure readings from hypertensive subjects were taken three times pre-test and three times post-test. The numbers in Table II represent an average/patient for the three blood pressure readings for both pre- and post-test.


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Table II. Average of Three Blood Pressure Readings for 10 Hypertensive Subjects (Pre-test and Post-test). Name Subject 1 Subjects Subject 3 Subject 4 Subject 5 Subject 6 Subject 7 Subject 8 Subject 9 Subject 10

Gender M M M M M F M M F F

Pre-average 135/82 149/95 152/90 145/86 143/76 140/81 154/90 149/68 135/79 142/84 144/83

Age 40 45 53 52 28 52 49 56 37 43

Post-average

mm

137/71 138/84 138/77 136/75 114/74 143/82 133/72 126/77 131/78 132/76

Discussion The results from the effects of NFJC and TNJ on ACE enzymes show that both noni samples inhibited ACE enzymes in a generally concentrationdependent manner. However, the inhibition of ACE enzymes with NFJC seems to be more pronounced than TNJ in the 1 and 5% concentrations. The inhibitory effects on ACE enzymes have been shown to lower hypertension and also lower hypertension-induce pathology (7). Similarly, results from our study showed both NFJC and TNJ inhibited A T and A T receptors. However, TNJ produced a greater inhibition of ATi compared to AT , while NFJC produced similar effects on both receptors. Concomitantly, the data show that TNJ selectively inhibited AT! over AT receptors, with IC values of 1.6 and 4.13%, respectively. The inhibition data also show that NFJC selectively inhibited ATi and A T receptors with IC values of 1.97 and 2.29%, respectively. The IC s for both NFJC and TNJ are much higher than that of the Saralasin, reference compound (0.119 nM). Such differences however, were not unexpected, since neither juice is a pure compound. However, unpublished data from our lab of noni fruit juice fractionation show that the inhibitory activities on angiotensin receptors are concentrated in the methanol extract. The methanol extract, in a 100 pg/mL concentration, inhibited both AT and A T receptors by 69 and 41%, respectively. The inhibitory effect of the methanol extract is significant since the concentration is one-tenth that of the 1% NFJC which showed to 44 and 7% inhibition of ATi and A T receptors, respectively. These results indicate that t

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NFJC is selective for AT\ receptors. This ATi receptor inhibitory selectivity has been shown to prevent diabetes-induce hypertension in mice (#). Moreover, it has been shown that A T receptor blockers suppress mediators of inflammation including ROS, C-reactive proteins, and increase the expression of inhibitory K B (JOThe inhibitory effects of NFJC and TNJ on both ACE enzymes, and the ATj and A T receptors, are possible mechanisms of action on hypertension. These effects, and perhaps others, may contribute to the lowering of blood pressure observed in the hypertensive subjects of this study. Results from this study show that the average blood pressure for the group was lowered from 144/83 to 132/76. Furthermore, except for the pre-test average diastolic pressure of subject 8, each hypertensive subjects' blood pressure was lowered. Though these results are preliminary, such reductions are significant when compared to normal blood pressure readings of 120/70. Additionally, the hypertensive subjects consumed only the test juices and no prescribed anti-hypertensive medications (Table II). These results suggest a need for other clinical and future studies of NFJC and TNJ on hypertension. 2


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Future Research Prospects The effects of noni fruit juice on normal, healthy people should be investigated to assess potentials for both adverse and beneficial effects on blood pressure. Additionally, based on our results, a large human clinical trial is warranted to investigate the effects of noni fruit juice on both female and male subjects who are seriously hypertensive, and are not taking prescribed medications, or who do not respond to other drug regimens. Finally, noni fruit juice effects on chymase, an enzyme that is also involved in hypertension, should be investigated, as many hypertensive patients also suffer from diabetic neuropathy, and do not respond to other hypertensive drug treatments.

Conclusions The present study has shown that Morinda citrifolia L noni products, NFJC and TNJ inhibit ACE enzymes and bind to and inhibit both angiotensin receptors AT! and AT . These inhibitory effects of noni on ACE enzymes and the angiotensin receptors may thus support the anecdotal therapeutic claims of traditional healers in Polynesia. Additionally, two ounces of TNJ in the morning before breakfast and before dinner were shown to lower high blood pressure in a group of diagnosed hypertensive subjects. Thus, TNJ may have the potential for use as an alternative for lowering high blood pressure. 2


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Acknowledgements Much appreciation is extended to Silivia Palu, a Tongan traditional healer, for sharing her knowledge of different ways of using noni for treatment of various diseases. We also thank Leeland White for helping in this manuscript, and the Founders of Morinda Holdings, Inc. for their financial support of this research.


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The Effects of Morinda citrifolia L. Noni on High Blood

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