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

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 antimotility 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 H-2 receptors, H+/K+ ATPase pump and voltage gated L-type calcium channels, while possesses moderate affinities (E-value >= 8 Kcal/mol) against histaminergic H-1, muscarinic M-1, M-3 and mu-opioid, whereas lower affinities (E-value >= 9.5 Kcal/mol) vs. calmodulin, adrenergic alpha(1), phosphodiesterase enzyme and dopaminergic D-2 receptors. Lupeol-3-acetate and beta-amyrin-3-(3'-dimethyl) butyrate observed weak affinities. Conclusion: In present study, M. zapota is reported to exhibits anti-diarrheal, anti-secretory, antispasmodic, anti-motility, anti-ulcer effects and computational binding affinities against gastrointestinal targets.