In-silico study of active phytochemicals and molecular mechanism of Hydrocotyle javanica Thunb.in treating MDR enterobacterial infection
TL;DR
It is highlighted that phytocompounds from Hydrocotyle javanica exhibit significant binding affinity toward key enterobacterial targets, along with favorable ADME and toxicity profiles, which suggest their potential as promising lead molecules for anti-enterobacterial drug development, warranting further experimental validation.
Abstract
Enterobacterial infections being severe, with a high mortality rate, particularly affecting ICU patients, and 80% newborns. These infections have multifactorial multi-drug resistance (MDR) mechanisms, which frequently causes current antibiotic therapies to fail, mortality rate remains high, and creating an urgent need for alternative multi-targeted therapies, such as plant-derived compounds to restore clinical effectiveness. This study aims to discover novel anti enteric compounds in Hydrocotyle javanica Thunb. (H. javanica) belongs to Apiaceae family and understanding their interaction mechanism with enterobacterial infection targeted genes, using network pharmacology with in-silico docking and molecular dynamics simulation approaches. Four bioactive compounds as tetracosanoic acid, alpha-Amyrenyl acetate, stigmasterol glucoside, stigmasterol were identified as potential therapeutic agents. Most of the compounds exhibited favourable pharmacokinetic properties, complying with Lipinski’s rule, with high bioavailability score 0.85 and non-toxic profiles. In-silico antibacterial prediction indicated both bacterial and bacteriostatic activities. A total of 53 common targets were identified with network analysis revealing key hub genes including HSD11B1, PTGS2,FDFT1,CYPHA1, and AKR1C2. Functional enrichment analysis showed significant involvement in immune and inflammatory pathways, particularly calcium signaling, MAPK signaling and reactive oxygen species related pathways. The docking result showed highest binding affinity, with stigmasterol showing highest score (-10.7 kcal/mol). A 100 ns molecular dynamics simulation further confirmed the stability of the stigmasterol-protein complex, with stable RMSD values 1–2 Å, low RMSF fluctuations and consistent hydrogen bonding, indicating sustained structural integrity. The present study highlights that phytocompounds from Hydrocotyle javanica exhibit significant binding affinity toward key enterobacterial targets, along with favorable ADME and toxicity profiles. These findings suggest their potential as promising lead molecules for anti-enterobacterial drug development, warranting further experimental validation.