Gomisin A as a multi‑target therapeutic agent: Pharmacological mechanisms, pharmacokinetics and network pharmacology (Review)

Gomisin A (GA; C23H28O7) is a principal bioactive dibenzocyclooctadiene lignan derived from Schisandra chinensis (Turcz.) Baill. (Wu Wei Zi), a herb traditionally used in Chinese medicine for its adaptogenic, hepatoprotective and detoxifying properties, particularly in treating fatigue, chronic cough and liver disorders. GA exhibits multi‑target potential against a spectrum of complex diseases. The present study aimed to assess the pharmacological profile, mechanisms, pharmacokinetics (PK) and computational docking of GA, emphasizing its potential as a multi‑target agent. A comprehensive literature search was performed in the PubMed and China National Knowledge Infrastructure database platforms. All mechanistic findings were appraised and stratified by supporting evidence strength, complemented by network pharmacology screening, molecular docking and molecular dynamics (MD) assessment of representative target complexes. GA exhibits polypharmacological properties, including hepatoprotective, anticancer, cardiovascular‑modulating, neuroprotective and anti‑inflammatory/antioxidant effects, with hepatoprotection representing the most robustly supported preclinical indication. GA modulates key signaling pathways such as the PI3K/AKT/mTOR, MAPK and ErbB receptor family pathways. Network pharmacology analysis identified STAT3, EGFR and mTOR as high‑priority candidate targets. Molecular docking predicted moderate‑to‑strong binding affinity across nine hub proteins, with that of EGFR reaching ‑7.7 kcal/mol. MD simulations further supported the conformational plausibility of the GA‑EGFR, GA‑GSK3β and GA‑STAT3 complexes. PK data identified limited oral bioavailability as a key translational bottleneck. GA holds promise as a multi‑target natural product. Advancing GA toward clinical translation requires addressing PK limitations through advanced delivery systems, alongside orthogonal validation of its predicted targets and preclinical and clinical evaluation.