Safety and Efficacy of Methanol Fraction of Moringa oleifera as Antihypertensive in L-NAME Induced Hypertensive Rabbits: Bedside to Bench, Implications for Bench Back to Bedside

Authors

  • A.D.A. Adedapo Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria
  • O.T. Jegede Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria
  • T.O. Omobowale Department of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
  • W. Nabofa Department of Physiology, University of Ibadan, Ibadan, Nigeria
  • A.A. Oyagbemi Department of Veterinary Physiology and Biochemistry, University of Ibadan, Ibadan, Nigeria
  • A.A. Adedapo Department of Veterinary Pharmacology and Toxicology, University of Ibadan, Ibadan, University of Ibadan, Ibadan, Nigeria

DOI:

https://doi.org/10.6000/1929-5634.2018.07.02.3

Keywords:

Moringa, hypertension, nitric-oxide, anti-oxidant, intention-to-treat, per protocol.

Abstract

Context: Hypertension, a global menace requires innovative research into the use of Moringa oleifera being promoted and traditionally used as alternative therapy.

Objective: To innovatively evaluate the mechanistic effect, safety and efficacy of the methanol fraction of M. oleifera (MMO) leaves on L-NAME induced hypertensive rabbits.

Methods: Rabbits were divided into six groups: Control, L-NAME alone, L-NAME with 100, 200 or 400 mg/kg of MMO and enalapril. Inclusion and exclusion criteria were similar baseline parameters and Day 3 systolic blood pressure (SBP) less than baseline SBP respectively. The primary outcome was a 10% reduction of SBP on Day 21. Enalapril group was excluded from analysis. Safety was assessed with liver and renal functions, hydrogen peroxide and nitric oxide concentrations to elucidate mechanistic effect.

Results: Moringa 100 mg/kg, 200 mg/kg and 400 mg/kg reduced SBP by 4.75, 18.00 and 15.25 mmHg (F=22.123, p=0.000). SBP control was achieved with MMO 200mg/kg, 14% reduction and 400mg/kg, 12% reduction. Nitric oxide concentration, 0.06, 0.094 and 0.114mmol (F= 30.255, p= 0.000) dose-dependently increased and was most predictive of SBP control (r2=0.802, p=0.000). Nitric oxide production was inversely related to heart/body weight ratio which was dose-dependently reduced. MMO reduced hydrogen peroxide and ALT level but no significant effect on urea, HDL, and TG.

Conclusion: MMO reduced SBP and dose-dependently increased nitric oxide concentration in L-NAME induced hypertensive rabbits. The effect may be mediated via activation of nitric oxide pathway. MMO demonstrated a potent anti-oxidant activity and safety. Effect on ventricular hypertrophy needs further evaluation.

References

World Health Report: Reducing risks, promoting healthy life. Geneva, Switzerland: World Health Organization, 2002. http: //www.who.int/whr/2002.

Adedapo A, Adeagbo AS, Adedapo AA. Use of botanical therapies among patients in secondary health facilities in south west Nigeria: Implications for medical education RPMP 2013; 35: 299-310.

Jed WF. Moringa oleifera: A review of the medical evidence for its nutritional, therapeutic and prophylactic properties. Trees of Life Journal 2005; 1(1): 5.

Anwar F, Latif S, Ashraf M, Gilani AH. “Moringa oleifera: a food plant with multiple medicinal uses. Phytotherapy Research 2007; 21(1): 17-25. https://doi.org/10.1002/ptr.2023

James A, Zinkankuba V. Moringa oleifera a potential tree for nutritional security in sub-Saharan Africa. Am J Res Comm 2017: 5(4). www.usa-journals.com. [Accessed on 2018 July 13].

Uphadek B, Shinkar DM, Patil PB, Saudagar RB. Moringa oleifera as a pharmaceutical excipient. Int J Curr Pharm Res 2018; 10(2): 13-16. https://doi.org/10.22159/ijcpr.2018v10i2.25883

Dangi SY, Jolly CI, Narayanan S. Antihypertensive activity of total alkaloids from the leaves of Moringaoleifera. Pharm Bio 2002; 40(02): 144-148. https://doi.org/10.1076/phbi.40.2.144.5847

Gilani AH, Aftab K, Suria A, et al. Pharmacological studies on hypotensive and spasmolytic activities of pure compounds from Moringa oleifera. Phytotherapy Research 1994; 8(2): 87-91. https://doi.org/10.1002/ptr.2650080207

Faizi S, Siddiqui BS, Saleem R, Siddiqui S, Aftab K, Gilani AH. Fully acetylatedcarbamate and hypotensive thiocarbamate glycosides from Moringa oleifera. Phytochemistry 1995; 38(4): 957-963. https://doi.org/10.1016/0031-9422(94)00729-D

Adedapo AA, Falayi OO, Oyagbemi AA. Evaluation of the analgesic, anti-inflammatory, antioxidant, phytochemical and toxicological properties of the methanol leaf extract of commercially processed Moringa oleifera in some laboratory animals. J Basic Clin Physiol Pharmacol 2015; 26: 491-499.

Shepherd JT, Katusic ZS. Endothelium-derived vasoactive factors: I. Endothelium-dependent relaxation. Hypertension 1991; 18: 76-85. https://doi.org/10.1161/01.HYP.18.5_Suppl.III76

Palmer RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988; 333: 664-66. https://doi.org/10.1038/333664a0

Jaiswal D, Rai PK, Kumar A, Mehta S, Watal G. Effect of Moringa oleifera Lam. Leaves aqueous extract therapy on hypoglycemic rats. J Ethnopharm 2009; 123(3): 392-396. https://doi.org/10.1016/j.jep.2009.03.036

Granger DL, Anstey NM, Miller WC, Weinberg JB. Measuring nitric oxide production in human clinical studies. Methods Enzymol 1999; 301: 49-61. https://doi.org/10.1016/S0076-6879(99)01068-X

von Zastrow M. Drug receptor and pharmacodynamics. In: Katzung BG, editor. Basic and clinical pharmacology. 14th ed. USA: McGraw-Hill 2018; p. 20-40.

Gupta R, Dubey DK, Kannan GM, Flora SJS. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse. Cell Biol Int 2007; 31(1): 44-56. https://doi.org/10.1016/j.cellbi.2006.09.007

Buxton ILO, Cheek DJ, Eckman D, Westfall DP, Sanders KM, Keef KD., NG-nitro L-arginine methyl ester and other alkyl esters of arginine are muscarinic receptor antagonists. Circ Res 1993; 72: 387-95. https://doi.org/10.1161/01.RES.72.2.387

Carceres A, Saraiva A, Rizzio S, Zabala L, De Leon E, Navy F. Pharmacological properties of Moringa oleifera. 2: screening for antispasmodic, anti-inflammatory and diuretic activity. J Ethnopharmacol 1992; 36(3): 233-237. https://doi.org/10.1016/0378-8741(92)90049-W

Lacy F, O’Connor DT, Schmid-Schonbein GW. Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens 1998; 16(3): 291-303. https://doi.org/10.1097/00004872-199816030-00006

Randriamboavonjy JI, Rio M, Pacaud P, Loirand G, Tesse A. Moringa oleifera seeds attenuate vascular oxidative and nitrosactive stresses in spontaneously hypertensive rats. Oxid Med Cell Longev 2017; 4129459.

Gupta SK. Intention-to-treat concept: A review. Perspective Clin Res 2011; 2(3): 109-112. https://doi.org/10.4103/2229-3485.83221

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Published

2018-08-16

How to Cite

Adedapo, A., Jegede, O., Omobowale, T., Nabofa, W., Oyagbemi, A., & Adedapo, A. (2018). Safety and Efficacy of Methanol Fraction of Moringa oleifera as Antihypertensive in L-NAME Induced Hypertensive Rabbits: Bedside to Bench, Implications for Bench Back to Bedside. Journal of Nutritional Therapeutics, 7(2), 51–58. https://doi.org/10.6000/1929-5634.2018.07.02.3

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