Arabian Journal of Chemistry (Aug 2023)
Pyrazoles containing organic extracts of Litsea glutinosa (Lour.) C. B. Rob enervate chemical-induced diarrhea in animal models evident in ligand-receptor interaction
Abstract
This research investigated the effect of organic extracts from Litsea glutinosa (Lour.) C. B. Rob bark and its five heterocyclic compounds on induced diarrheal models. The bark of L. glutinosa was extracted with chloroform, ethyl acetate, and methanol. The resultant extracts were examined for disc-diffusion-guided activity against diarrhea-causing bacteria and chemical-induced anti-diarrheal properties in castor oil- and magnesium sulfate-induced diarrheal models. The effect of the extracts on gastrointestinal motility was tested in activated charcoal meal and barium sulfate milk models. The effects of the extracts on electrolytes (Na+, K+, Cl- and HCO3–), creatinine, triglycerides (TG), C-reactive protein (CRP), and immunoglobulin E (IgE) were assessed in the blood serum of treated animals. From the GC–MS analysis of the L. glutinosa methanol extract, five heterocyclic compounds were selected, and their interactions with target receptors were investigated using molecular docking techniques. The methanol extract (MExLG) showed the highest zone of inhibition for Shigella dysentriae (ZOI, 24 ± 0.9 mm) and E. coli (ZOI, 16.00 ± 1.14 mm), Salmonella paratyphi (18.23 ± 3.06 mm) and Vibrio cholerae (22.10 ± 2.62 mm). For both castor oil- and barium sulfate-induced diarrhea, MExLG achieved the highest levels of diarrheal inhibition 82.5% and 77.33%, respectively. MExLG showed the best in Na+, K+, Cl-, and HCO3– equivalence. Serum creatinine, TG, CRP and IgE levels were significantly (P < 0.05) restored by both MExLG and ethyl acetate extract (EAxLG). Out of five compounds, 1-(2-Fluorophenyl)pyrazole-4-carboxylic acid had the closest ligand-receptor interaction to that of the standard anti-diarrheal drug loperamide. The results demonstrate that the 1-(2-Fluorophenyl)pyrazole-4-carboxylic acid of MExLG could be positioned as a potential anti-diarrheal target through further affirmation in a dose–response cell-line study.
