Gomisin D

Gomisin D (CAS 60546-10-3) is a dibenzocyclooctadiene lignan compound isolated from Schisandra chinensis, characterized by favorable in vivo absorption and a prolonged half-life. Molecular docking studies (CDOCKER energy: 49.9404) and surface plasmon resonance (SPR) analysis have demonstrated that Gomisin D exhibits high-affinity binding to PDGFRβ (KD = 3.3 × 10⁻⁵ M), with the binding process involving multiple interactions, including hydrogen bonding, pi-anion, and pi-pi stacking. The primary mechanism of action of Gomisin D is the targeting of PDGFRβ and modulation of the PDGF-BB/PDGFRβ signaling pathway, resulting in the inhibition of downstream phosphorylation of AKT, ERK, and p38 MAPK. Consequently, both in vitro and in vivo experiments have shown that Gomisin D dose-dependently suppresses the activation and proliferation of hepatic stellate cells (HSCs), promotes apoptosis of activated HSCs, and reduces the expression of α-SMA and type I collagen. Additionally, it downregulates the levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Notably, Gomisin D significantly ameliorates CCl₄-induced hepatic fibrosis in mice, as evidenced by decreased serum ALT and AST levels, alleviation of hepatic histopathological damage and collagen deposition, and the absence of significant tissue toxicity at a dosage of 50 mg/kg.

References:

[1] Wang R, Liu F, Chen P, Li S, Gu Y, Wang L, Chen C, Yuan Y. Gomisin D alleviates liver fibrosis through targeting PDGFRβ in hepatic stellate cells. Int J Biol Macromol. 2023 Apr 30;235:123639. doi: 10.1016/j.ijbiomac.2023.123639. Epub 2023 Feb 22. PMID: 36822287.