Elucidating the MultiPathway Therapeutic Potential of Trichosantheskirilowii Bioactives in Intestinal Obstruction via Network Pharmacology and Molecular Dynamics.

Abstract

Intestinal obstruction (IO) disrupts normal intestinal transit and involves dysmotility, mucosal stress, and inflammation. This computational workflow evaluated a 10-compound Trichosanthes kirilowii docking panel, a filtered disease-target set, MOE docking validation, and 100 ns MOE molecular dynamics and MM/GBSA endpoint analyses. GeneCards filtering (relevance >= 10) and OMIM curation yielded a primary disease union of 756 genes; 31 targets overlapped with a broadened 203-target herb-associated set, and the overlap was significant by hypergeometric testing (p = 6.38 × 10-11). Docking across ACTB, AKT1, ALB, IL6, MYC, PTGS2, and TNFR1/TNFRSF1A showed strongest overall performance for β-D-glucopyranosyl-α-spinasterol (mean score -8.19 kcal/mol), followed by Stigmast-7-en-3β-ol 3-O-β-D-glucopyranoside, Cucurbitacin B, Bryonolic acid, and Cucurbitacin D. Redocking validation passed for ACTB, AKT1, ALB, PTGS2, and TNFR1, while IL6 and MYC were evaluated using alternative site validation. These results support a multicompound, multitarget hypothesis requiring experimental confirmation.