Network Pharmacology Reveals the Mechanism of Sini Decoction Against Aconitum carmichaelii Debeaux-Induced...

Sini Decoction (SND), particularly its components Zingiber officinale Roscoe and Glycyrrhiza uralensis Fisch, is traditionally used to mitigate the cardiotoxicity induced by Aconitum carmichaelii Debeaux, but the underlying mechanism remains incompletely understood. This study employed an integrative strategy combining network pharmacology to identify core targets, molecular docking to evaluate compound-target interactions, and in vitro experiments using H9c2 cardiomyocytes for functional validation. Network analysis identified 301 potential targets associated with aconitine-induced cardiotoxicity, with TNF, IL6, and AKT1 as core targets. Z. officinale Roscoe and G. uralensis Fisch shared 35 cardioprotective targets with aconitine toxicity, including STAT3, AKT1, and IL6. Molecular docking demonstrated strong binding affinities of 6-gingerol, a key bioactive compound of Z. officinale Roscoe, to core targets such as SRC and MAPK3. In vitro, 6-gingerol significantly alleviated aconitine-induced cytotoxicity, reduced lactate dehydrogenase release, and restored AKT and MAPK phosphorylation. In addition, it modulated the inflammatory cytokines TNF and IL6 and the apoptosis-related genes Bcl2 and Bax. These findings indicate that 6-gingerol exerts protective effects against aconitine-induced cardiotoxicity by regulating the AKT/MAPK signaling pathway and suppressing inflammation and apoptosis, providing mechanistic evidence for the detoxifying property of Sini Decoction.