Pharmacological and computational evaluation of Sapodilla and its constituents for therapeutic potential in hyperactive gastrointestinal disorders

Document Type : Original Article

Authors

Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad

Abstract

Objective(s): This study was designed to investigate various gastrointestinal effects of Manilkara zapota (Sapodilla), exploring its anti-diarrheal, anti-secretary, anti-spasmodic, anti-ulcer and anti-motility potential.
Materials and Methods: Antidiarrheal and anti-secretary activities were investigated using castor oil induced diarrhea and castor oil induced fluid accumulation. Isolated rabbit jejunum tissues (antispasmodic) were employed for in vitro experiments. Antiulcer, antimotility and molecular docking were performed using ethanol-HCl induced ulcer assay, charcoal meal transit time and Auto Doc Vina.
Results: Mz.Cr exhibited protection against castor oil-induced diarrhea (P<0.05 vs. saline group) and dose-dependently inhibited intestinal fluid secretions (P<0.001 vs. castor oil group). Mz.Cr caused relaxation of spontaneous and K+ (80 Mm)-induced contractions with EC50 values of 0.11mg/ml (0.08-0.1, n=4) and 0.16 mg/ml (0.09-0.2, n=4) respectively (*P<0.05**P<0.01 ***P<0.001). It showed protective effect against gastric ulcers induced by ethanol-HCl (P<0.001 vs. saline group). Mz.Cr reduced distance travelled by charcoal meal (P<0.001 vs. saline group). Plant constituents: caffeoylquinic acid and methyl 4-O-galloylchlorogenate showed high binding affinities (E-value≥-6.5 Kcal/mol) against histaminergic H2 receptors, H+/K+ ATPase pump and voltage gated L-type calcium channels, while possesses moderate affinities (E-value≥8 Kcal/mol) against histaminergic H1, muscarinic M1, M3 and mu-opioid, whereas lower affinities (E-value≥9.5 Kcal/mol) vs. calmodulin, adrenergic α1, phosphodiesterase enzyme and dopaminergic D2 receptors. Lupeol-3-acetate and β-amyrin-3-(3’-dimethyl) butyrate observed weak affinities.
Conclusion: In present study, M. zapota is reported to exhibits anti-diarrheal, anti-secretory, anti-spasmodic, anti-motility, anti-ulcer effects and computational binding affinities against gastrointestinal targets.

Keywords

References

1. Dwivedi SN, Dwivedi S, Patel PC. Medicinal Plants used by the tribals and rural people of Satna district, Madhya Pradesh for the treatment of gastrointestinal disease and disorders. Nat Prod Res. 2006;5:60-63.
2. Cseke L, Podila G. MADS-box genes in dioecious aspen II: a review of MADS-box genes from trees and their potential in forest biotechnology. 2004.
3. Colegate SM, Molyneux RJ. An introduction and overview. In Bioactive Nat Products. 2007;10-18.
4. Nascimento GG, Locatelli J, Freitas PC, Silva GL. Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria. Braz J Microbiol. 2000;31:247-256.
5. Chanda S, Nagani K. Antioxidant capacity of Manilkara zapota L. leaves extracts evaluated by four in vitro methods. Nat. and science. 2010;8:260-266.
6. Ma J, Luo X-D, Protiva P, Yang H, Ma C, Basile MJ, Weinstein IB, Kennelly ED. Bioactive novel polyphenols from the fruit of Manilkara zapota (Sapodilla). J Nat Prod. 2003;66:983-986.
7. Riaz U, Zahid H, Zafar I, Javid H, Khan F, Naeem K. Traditional uses of medicinal plants in Darra Adam Khel NWFP Pakistan. J Med Plants Res. 2010;4:1815-1821.
8. Pontes PV, Moreira RFA, Trugo LC, Maria CABD. The content of chlorogenic acids in tropical fruits. J Sci Food Agric. 2002;82:1177-1181.
9. Fayek NM, Monem ARA, Mossa MY, Meselhy MR. New triterpenoid acyl derivatives and biological study of Manilkara zapota (L.) Van Royen fruits. Pharmacognosy Res. 2013; 5:55-59.
10. Care A, Committee U. Guidelines for the capture, handling, and care of mammals as approved by the American Society of Mammalogists.
J Mammal. 1998; 79:1416-1431.
11. Evans W. 1996. Deterioration of stored Drugs Trease and Evans Pharmacognosy: London:WB Saunders Ltd.
12. Umer S, Tekewe A, Kebede N. Antidiarrhoeal and antimicrobial activity of Calpurnia aurealeaf extract. BMC Complement Altern Med. 2013;13:21-24.
13. Teke GN, Kuiate JR, Ngouateu OB, Gatsing D. Antidiarrhoeal and antimicrobial activities of Emilia coccinea (Sims) G. Don extracts. J Ethnopharmacol. 2007;112:278-283.
14. Mehmood MH, Munir S, Khalid UA, Asrar M, Gilani AH. Antidiarrhoeal, antisecretory and antispasmodic activities of Matricaria chamomilla are mediated predominantly through K+-channels activation. BMC Complement Altern Med. 2015;15:75.
15. Ateufack G, Mokam ECD, Mbiantcha M, Feudjio RBD, David N, Kamanyi A. Gastroprotective and ulcer healing effects of Piptadeniastrum Africanumon experimentally induced gastric ulcers in rats. BMC Complement Altern Med. 2015;15:214.
16. Ali B, Bashir A. The effect of some α2‐adrenoceptor agonists and antagonists on gastrointestinal transit in mice: influence of morphine, castor oil and glucose. Clin Exp Pharmacol Physiol. 1993;20:1-6.
17. Guideline O. For the testing of chemicals, Guidance document on acute oral toxicity. Environmental health and safety monograph series on testing and assessment. 2008;1-27.
18. Duhovny D, Nussinov R, Wolfson HJ. Efficient unbound docking of rigid molecules. Paper presented at the International workshop on algorithms in bioinformatics. 2002v.
19. Capasso F, Mascolo N, Izzo AA, Gaginella TS. Dissociation of castor oil‐induced diarrhoea and intestinal mucosal injury in rat: effect of NG‐nitro‐L‐arginine methyl ester. Br J Pharmacol. 1994;113:1127-1130.
20. Khan M, Khan Au, Rehman Nu, Gilani AH. Pharmacological basis for medicinal use of Lens culinarisin gastrointestinal and respiratory disorders. Phytother Res. 2014;28:1349-1358.
21. Joseph N, Esther NLT, Benoît NT, Désiré DDP, Bibi-Farouck, AO, Théophile D, Pierre K. Effects of the aqueous extract of Pittosporum mannii Hook. f. (Pittosporaceae) stem barks on spontaneous and spasmogen-induced contractile activity of isolated rat duodenum. J Ethnopharmacol. 2015;172:1-9.
22. Adinortey MB, Ansah C, Galyuon I, Nyarko A.  In vivo models used for evaluation of potential anti gastroduodenal ulcer agents. Ulcers. 2013;2013:1-12.
23. Izzo AA, Mascolo N, Capasso R, Germanò MP, De Pasquale R, Capasso F. Inhibitory effect of cannabinoid agonists on gastric emptying in the rat. Naunyn Schmiedebergs Arch Pharmacol. 1999;360:221-223.
24. Nwinyi F, Binda L, Ajoku G, Aniagu S, Enwerem N, Orisandipe A, Kubmarawa D, Gamaniel KS. Evaluation of the aqueous extract of Boswellia dalzieliistem bark for antimicrobial activities and gastrointestinal effects. Afr J Biotechnol. 2004;3:284-288.
25. Pietta PG. Flavonoids in medicinal plants. In: Rice-Evans CA, Packer L, editors. Flavonoids in health and disease. New York: Dekker; 1998. p.61-110.
26. Bajorath J.  Integration of virtual and high-throughput screening. Nat Rev Drug Discov. 2002; 1:882-894.
27. Guo F, Li SC, Wang L, Zhu D. Protein-protein binding site identification by enumerating the configurations. BMC Bioinformatics. 2012;13:158-182.
28. Patil R, Das S, Stanley A, Yadav L, Sudhakar A, Varma AK. Optimized hydrophobic interactions and hydrogen bonding at the target-ligand interface leads the pathways of drug-designing. PLoS One. 2010;5:12029-12038.
29. Hudson JW, Golding GB, Crerar MM. Evolution of allosteric control in glycogen phosphorylase. J Mol Biol.1993;234:700-721.
30. Barford D, Johnson L. The allosteric transition of glycogen phosphorylase. Nature. 1989;340:609-616.
31. Saqib U, Siddiqi MI. Probing ligand binding interactions of human alpha glucosidase by homology modeling and molecular docking. Int J Biol. 2008;2:116-121.
32. Choi J, Park Y, Lee HS, Yang Y, Yoon S. 1, 3-Diphenyl-1H-pyrazole derivatives as a new series of potent PPARγ partial agonists. Bioorganic Med. Chem. 2010;18:8315-8323.
Iranian Journal of Basic Medical Sciences
Volume 23, Issue 2
February 2020
Pages 224-235

Files

Share

How to cite

Statistics