Persea Americana Seeds Cause Ileal Smooth Muscle Relaxation Via Stimulation of α-1 Adrenoceptors

Abstract

The effect of methanol extract of P. americana seeds on isolated ileal smooth muscle was studied for isometric response using 10 adult rabbits of both sexes. Reactivity and agonist-antagonist responses of rabbit ileum to the extract were determined in this study. The affinity, effective concentration to give 50% response (EC₅₀) and maximum response were calculated from the concentration response curves (CRC) obtained. The result for the reactivity study showed the seed extract of P. americana caused concentration dependent relaxation of isolated rabbit ileum with threshold responses at concentration of 1×10⁻⁹ mg/ml and 120 mg/ml respectively. The extract-antagonist study showed an upward and right shift in CRC in the presence of phenoxybenzamine, a non-selective adrenergic antagonist, with the EC₅₀ increased from 5.01 mg/ml to 12.59 mg/ml and affinity decreased from 0.20 to 0.08. Extract-antagonist study also showed a right and upward shift in the CRC with a greater magnitude in the presence of prazosin, an α1-adrenergic antagonist, with EC₅₀ increased from 0.32 mg/ml to 25.12 mg/ml and a consequential decrease in the affinity from 3.13 to 0.04. In the presence of propranolol, a β-adrenergic antagonist, a downward and left shift in the CRC was observed with the EC₅₀ and PA2 remaining constant at 0.1 mg/ml and 10 respectively. P. americana concentration-dependently reduced or inhibited gastric motility, increasing transit time which is important for food absorption, thus a pro-nutritive and antispasmodic effect. The interaction with α1-adrenoceptors is beneficially in heart failure management. The plant can be developed as a drug candidate for management of hypertension.

Keywords

gastrointestinal pharmacology - G protein-coupled receptors - drug research

• References

• 1 Chen Y, Ju L, Rushdi M. et al. Receptor-mediated cell mechanosensing. Mol Biol Cell 2017; 28: 3134-3155
• 2 Fukata Y, Mutsuki A. Kaibuch. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non muscle cells. Trends Physiolog Sci 2001; 22: 32-39
• 3 Jin L, Linder AE, Mills TM. et al. Inhibition of the tonic contraction in the treatment of erectile dysfunction. Exp Opin Therap Targets 2003; 7: 265-276
• 4 Reynaud Y, Fakhry J, Fothergill L. et al. The chemical coding of 5-hydroxytryptamine containing enteroendocrine cells in the mouse gastrointestinal tract. Cell Tissue Res 2016; 364: 489-497
• 5 Canals M, Poole DP, Veldhuis NA. et al. G-Protein–Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases: Reviews in Basic and Clinical Gastroenterology and Hepatology. Gastroenterol 2019; 156: 1600-1616. doi:https://doi.org/10.1053/j.gastro.2019.01.266
• 6 Kennedy L, Hodges K, Meng F. et al. Histamine and histamine receptor regulation of gastrointestinal cancers. Transl Gastrointest Cancer 2012; 1: 215-227
• 7 Sanger GJ, Broad J, Kung V. et al. Translational neuropharmacology: The use of human isolated gastrointestinal tissues. Br J Pharmacol. 2013; 168: 28-43 doi:10.1111/j.1476-5381.2012.02198.x
• 8 Baldi F, Bianco MA, Nardone G. et al. Focus on acute diarrhoeal disease. World J Gastroenterol 2009; 15: 3341-3348
• 9 Camilleri M, Sellin JH, Barrett KE. Pathophysiology, evaluation, and management of chronic watery diarrhea: Reviews in basic and clinical gastroenterology and hepatology. Gastroenterol 2017; 152: 515-532. doi:10.1053/l.gastro.2016.10.014
• 10 Meylan M, Georgieva TM, Reist M. et al. Distribution of mRNA that codes for subtypes of adrenergic receptors in the gastrointestinal tract of dairy cows. Amer J Vet Res 2004; 65: 1142-1150
• 11 Chen-Izu Y, Xiao RP, Izu LT. et al. G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels. Biophys J 2000; 79: 2547-2556
• 12 Ojewole JA, Kamadyaapa DR, Gondwe MM. et al. Cardiovascular effects of Persea americana Mill (Lauraceae) (avocado) aqueous leaf extract in experimental animals. Cardiovasc J Afr 2007; 18: 69-76
• 13 Yasir M, Das S, Kharya MD. The phytochemical and pharmacological profile of Persea americana Mill. Pharmacogn Rev 2010; 4: 77-84 doi:10.4103/0973-7847.65332
• 14 Imafidon KE, Amaechina FC. Effects of aqueous seed extract of Persea americana Mill. (Avocado) on blood pressure and lipid profile in hypertensive rats. Adv Biol Res 2010; 4: 116-121
• 15 Oridupa OA, Falade FB, Oyagbemi A. et al. Annona muricata L. leaves or Curcuma longa L. rhizomes ameliorates oxidative stress associated with hypertension in uninephrectomized Wistar rats daily loaded with sodium chloride. Eur J Med Plants 2019; 26: 1-13
• 16 Rengo G. The adrenergic system in cardiovascular pathophysiology: a translational science point of view. Front Physiol 2014; 5: 356 doi:10.3389/fphys.2014.00356
• 17 Saba AB, Oridupa OA. Pharmacological reactivity of isolated guinea pig ileum to ethanol leaf extracts of Amaranthus caudatus and Solanum melongena . Nig J Physiol Sci 2012; 27: 73-78
• 18 Oridupa OA, Saba AB. Relaxant effect of Lagenaria breviflora Roberty fruit pulp and seeds on isolated rabbit ileum. Sok J Vet Sci 2013; 11: 21-27
• 19 Rang HP, Dale MM, Ritter JM. et al. Noradrenergic transmission. In: Rang and Dale’s Pharmacology. 6th edition Elsevier Churchill Livingstone Press; 2007: 169-170
• 20 Okafor JC, Arazu RC, Ibuzo J. et al. Checklists of medicinal plants of Nigeria and their uses. James Enugu Nigeria: 2005. Pp 1-97
• 21 Huang SC. Endothelin receptors in gastrointestinal smooth muscle. Curr Prot Pep Sci 2005; 6: 547-557
• 22 Giaroni C, Knight GE, Ruan HZ. et al. P227 receptors in the murine gastrointestinal tract. Neuropharmacol 2005; 43: 1313-1323
• 23 McDonnell B, Hamilton R, Fong M. et al. Functional evidence for purinergic inhibitory neuromuscular transmission in the mouse internal anal sphincter. Gastroint Liv Physiol 2008; 294: G1041-G1051
• 24 O’Connell TD, Jensen BC, Baker AJ. et al. Cardiac α1-Adrenergic Receptors: Novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev 2014; 66: 308-333. doi:10.1124/pr.112.007203
• 25 SoRelle R. National Heart, Lung, and Blood Institute halts part of antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). Circulation 2000; 101: E9025. doi:10.1161/01.cir.101.12.e9025
• 26 Davis BR, Cutler JA, Furberg CD. et al. ALLHAT Collaborative Research Group Relationship of antihypertensive treatment regimens and change in blood pressure to risk for heart failure in hypertensive patients randomly assigned to doxazosin or chlorthalidone: further analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial. Ann Intern Med 2002; 137: 313-320 doi:10.7326/0003-4819-137-5_part_1-200209030-00006
• 27 Olushola AI, Aderibigbe KO, Stephen SO. et al. Biochemical effects of aqueous extract of Persea americana (Mill) on the myocardium of left ventricle of high salt–fed adult Wistar rats. J Evidence-Based Compl Altern Med 2017; 22: 765-769. doi:https://doi.org/10.1177/2156587217733884.