Phytomedicine Plus (Aug 2021)
Gastric H+, K+-ATPase inhibitory effects of the active constituent isolated from Potentilla fulgens roots: An in vivo and in silico molecular docking studies
Abstract
Background and objective: Potentilla fulgens (Rosaceae) is an edible medicinal herb which is widely used in Indian and Chinese traditional medicine for treating gastric ulcer, diabetes, cancer and diarrhea. Literature reveals that the crude ethanolic extract (EPF) of the plant possessed promising gastroprotective effects in rodents. However, the actual chemical marker with a probable mechanism of action responsible for its anti-secretory efficacy is still left unexplored. Hence, the present investigation was aimed to examine the phytoconstituents responsible for gastric anti-secretory effect incorporating in vivo study supported by in silico molecular docking techniques. Methods: Experimentally, four EPF bioactive fractions were tested viz. chloroform (PFCH), ethylacetate (PFEA), n-butanol (PFBu) and aqueous (PFAq). As per the bioactivity guided assay, the most bioactive fraction (PFEA) was subjected to column chromatography and the isolated component (-) epicatechin (EC) was screened for its effects on gastric ulceration induced by pyloric ligation (PL) and absolute ethanol. Various gastric secretion parameters such as gastric juice volume, pH, H+, K+-ATPase activity and histamine levels were determined. In silico molecular docking study was performed to predict the binding efficacy of EC responsible for the inhibition of H+, K+-ATPase enzyme. Results: Results from the PL model indicate that PFEA, PFBu and EC showed significant gastroprotective effect (p<0.05) when compared to the ulcer control group with percentage protection of 70.16%, 55.39% and 67.00% respectively. The mechanism of action underlying the anti-secretory effect was attributed to EC (20 mg/kg, p.o.) that showed significant (p<0.05) decrease in gastric juice volume and H+, K+-ATPase activity. In silico studies revealed that EC exhibit promising inhibitory effect (binding energy of −8 kcal/mol) towards H+, K+-ATPase. This may be due to higher number of H-bond interactions (with Asp 137, Val 341, Glu 795 and Leu 811) and π-π stacking (with Tyr 799) with the amino acids of active site of H+, K+-ATPase. Conclusion: Thus, the present study indicates that the mechanism of gastroprotective activity of EC is attributed towards the potassium competitive acid blocker.
