Sublingual Dripping Pill Formulation of Ganoderma amboinense Fruiting Body Extract Attenuates CCl4-Induced Liver Fibrosis via Multi-Pathway Regulation

Liver fibrosis remains difficult to treat, in part because many hepatoprotective triterpenoids suffer from poor oral bioavailability and lack of optimized delivery formats. Ganoderma amboinense is a rare “antler” reishi species long valued in Eastern traditions yet scarcely studied for its phytochemical and pharmacological potential. Here, we report the first investigation of an ethanol-extracted G. amboinense sublingual dripping pill formulation (GDP) in a carbon-tetrachloride (CCl4)–induced mouse model of liver fibrosis. Mice treated with GDP at one- and five-times the human equivalent dose were compared to groups receiving unprocessed G. amboinense powder (GP) or purified ganoderic acid A (GA-A). GDP significantly prevented CCl4-induced weight loss and hepatomegaly, normalizing liver-to-body weight ratios and serum AST/ALT activities (p < 0.05). Histological evaluation showed that GDP markedly reduced hepatocellular necrosis and collagen deposition, restoring tissue architecture. Furthermore, GDP suppressed hepatic expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, COX-2) and profibrotic markers (TGF-β1, CTGF, α-SMA) to levels comparable with or superior to GA-A. These results demonstrate that a dripping pill dosage form can effectively deliver G. amboinense triterpenoids and unlock their hepatoprotective activity, supporting further development of GDP as a novel liver-support nutraceutical.