Reparative and Toxicity-Reducing Effects of Liposome-Encapsulated Saikosaponin in Mice with Liver Fibrosis

Saikosaponin d (SSd), a primary active component of the Chinese herb Bupleurum falcatum, has antitumor and anti-liver fibrosis effects. However, the toxicity of SSd at high doses can induce conditions such as metabolic disorders and hemolysis in vivo, thus hampering its clinical use. This study investigated the toxicity-reducing effects of liposome encapsulation of pure SSd and the therapeutic action of SSd-loaded liposomes (Lipo-SSd) in liver fibrosis in vitro and in vivo. Lipo-SSd (diameter, 31.7 ± 7.8 nm) were prepared at an entrapment efficiency of 94.1%. After 10-day incubation, a slow release profile of 56% SSd from Lipo-SSd was observed. The IC50 of SSd on hepatic stellate cells was approximately 2.9 μM. Lipo-SSd exhibited much lower cytotoxicity than did pure SSd. In the in vivo toxicity assay, Lipo-SSd significantly increased mice survival rate and duration compared with pure SSd at the same dose. These in vitro and in vivo data all indicate that liposomal encapsulation can reduce the cytotoxicity of SSd. The histopathological analysis results demonstrated that in mice with thioacetamide-induced liver fibrosis, Lipo-SSd exerted more obvious fibrosis- and inflammation-alleviating and liver tissue-reparative effects than did pure SSd; these effects are potentially attributable to the sustained release of SSd. In conclusion, Lipo-SSd fabricated here have anti-liver fibrosis effects and lower toxicity compared with that of pure SSd.

Keywords: Saikosaponin; cytotoxicity; liposome; liver fibrosis.