Protective potential of ethylacetate extract of Abrus precatorius (Linn) seeds against HCl/EtOH-induced gastric ulcer via pro-inflammatory regulation: In vivo and in silico study

Gastric ulcer is the most common gastrointestinal disorder of the stomach which has become global health challenge. Management with natural therapeutic agents such as Abrus precatorius seed extract through regulation of pro-inflammatory cytokines messenger ribonucleic acid (mRNA) expression would provide relief to patients with ulcer. However, there are several reports on pharmacological efficacy of A. precatorius seed. Up-regulation of pro-inflammatory genes and elevation of the inflammatory cytokines are significant mechanism of ulcer pathogenesis. This work sought to investigate the anti-ulcerative efficacy of ethylacetate extract of Abrus precatorius seed in hydrochloric acid/Ethanol (HCl/EtOH)-induced ulcerative rats via regulation of inflammatory genes. Experimental animals were administered 100 and 200 mg/kg b.w of EEAPS, diclofenac and cimetidine (50 mg/kg b.w) for period of 8 days. One hour after the last administration, EtOH/HCl was administered orally to induce gastric injury. Stomach ulceration score, histological changes and messenger ribonucleic acid (mRNA) expression were evaluated using standard procedures. The bioactive compounds present in EEAPS were identified using high performance liquid chromatography (HPLC) followed by molecular docking against cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nuclear factor kappa (NF-KB), interleukin-1β (IL-1β) and Tumor Necrosis Factor alpha (TNF-α) proteins. Exposure of rats to EtOH/HCl significantly (P < 0.05) elevates stomach ulceration scores and up-regulation of COX-2, INOS, IL-1β, NF-kb and TNF-α mRNA expression compared to normal control rats. The alterations were reversed in animals pre-treated with EEAPS and standard drugs, 200 mg/kg b. w of EEAPS showed the highest ameliorative efficacy. HPLC analysis of EEAPS revealed the presence of 5 compounds which showed varying degrees of binding affinities when docked against target proteins. Apigenin showed the highest binding affinity (-9.6 kcal/mol) against iNOS. The results of the in silico pharmacokinetic and drug likeness properties of the compounds reveals that, these compounds are potential drug candidates. Abrus precatorius seed might be a source of new drugs and natural remedy against gastric injury through inhibition of inflammatory reactions.