Chidimma E Ominyi^1,2 , Chinelo J Onyia², Frances Ojobor¹, Lilian I Nweke^1,3, Charles O Nnadi^1,4

Abstract

Purpose: To evaluate the anti-ulcer potential of Crassocephalum crepidioides by integrating both experimental and computational approaches. Methods: Dried cold-macerated methanol extract of C. crepidioides was fractionated to obtain ethyl acetate, methanol and n-hexane fractions. The acute toxicity of the extract was determined by the Lorke method. The extract and ethyl acetate fraction were fingerprinted using the high-performance liquid chromatography-diode array detector (HPLC-DAD) technique. The in vivo anti-ulcer activity in Wistar rats was evaluated using ethanol- and indomethacin-induced models with oral Tween 80 and omeprazole as controls. The identified compounds were docked on human prostaglandin E receptor EP4, Helicobacter pylori urease and monoclonal porcine pepsin ulcerogenic factor targets for in silico studies. Results: The extract was safe up to a 5000 mg/kg dose, with no lethality or delayed overt toxicity. The HPLC-DAD identified fingerprints such as flavonoids (quercetin, kaempferol, rutin and catechin), phenolic acids (chlorogenic, gallic, ellagic and caffeic acids), and many others. The ethyl acetate fraction (500 mg/kg) elicited the highest ulcer inhibition (72.92 %), significantly (p < 0.05) higher than 20 mg/kg omeprazole (56.25 %) in the indomethacin-induced model. The binding parameters of the ligands showed that among the flavonols and phenolic acids, rutin (E = -12.12 kcal/mol, Ki = 0.001 µM) and chlorogenic acid (E = -10.13 kcal/mol, Ki = 0.037 µM) respectively elicited significantly stronger binding to the EP4, a defensive ulcerogenic protein target. Conclusion: In vivo and in silico evidence show that C. crepidioides possesses potent gastro-protective properties, which could be attributed to its polyphenolic constituents.