Hang Zeng,Yiming Jiang,Pan Chen,Xiaomei Fan,Dongshun Li,Aiming Liu,Xiaochao Ma,Wen Xie,Peiqing Liu,Frank J Gonzalez,Min Huang,Huichang Bi
Background and Purpose Currently, ursodeoxycholic acid and obeticholic acid are the only two FDA-approved drugs for cholestatic liver diseases. Thus, new therapeutic approaches need to be developed. Here we have evaluated the anti-cholestasis effects of Schisandrol B (SolB), a bioactive compound isolated from Schisandra sphenanthera . Experimental Approach Hepatoprotective effect of SolB against intrahepatic cholestasis, induced by lithocholic acid (LCA), was evaluated in mice. Metabolomic analysis and gene analysis were used to assess involvement of pregnane X receptor (PXR). Molecular docking, cell-based reporter gene analysis and knockout mice were used to demonstrate the critical role of the PXR pathway in the anti-cholestasis effects of SolB. Key Results SolB protected against LCA-induced intrahepatic cholestasis. Furthermore, therapeutic treatment with SolB decreased mortality in cholestatic mice. Metabolomics and gene analysis showed that SolB accelerated metabolism of bile acids, promoted bile acid efflux into the intestine, and induced hepatic expression of the PXR-target genes Cyp3a11, Ugt1a1 , and Oatp2, which are involved in bile acid homeostasis. Mechanistic studies showed that SolB activated human PXR and up-regulated PXR target genes in human cell lines. Additionally, SolB did not protect Pxr -null mice from liver injury induced by intrahepatic cholestasis, thus providing genetic evidence that the effect of SolB was PXR-dependent. Conclusion and Implications These findings provide direct evidence for the hepatoprotective effects of SolB against cholestasis by activating PXR. Therefore, SolB may provide a new and effective approach to the prevention and treatment of cholestatic liver diseases.
A significant quantity of residues will produce when volatile oil in Schisandra chinensis fruit is extracted by steam distillation. It is important to investigate the residues for potential use. Currently, there is an increasing demand for anti-photoaging products due to the skin damage caused by UV radiation. In this paper, the ingredients of the residues were investigated, and the anti-photoaging activities of residues extracts were studied. The results showed that the residues still contained notable amounts of lignans, flavonoids, and organic acids. In the extracted fraction of dichloromethane (DE), the residues contained higher amounts of schizandrol B and schisantherin A compared to the fresh fruit. The levels were particularly high at 17.39 ± 0.02 and 52.58 ± 0.04 mg/ml, respectively. By lowering the amount of matrix metalloproteinase-1 (MMP-1), reactive oxygen species (ROS) accumulation, and type I collagen (COL-I) loss in fibroblasts, the residues showed targeted benefits in the fight against skin photoaging. In particular, the DE-R phase of residues was very successful in raising the level of COL-I, matching or even exceeding that of retinol (ROL) and undistilled fresh fruits. Protocatechuic acid, schizandrol A, schizandrol B, schisantherinA, schisandrin A and schizandrin B were found to have a significant correlation with the anti-photoaging ability of residues. Particularly, there was a strong and significant correlation between an increase in COL-I and schizandrol B (|ρ| = 0.829*) and schisantherin A (|ρ| = 0.928**), and the distillation procedure has the potential to increase the amount of schizandrol B and schisantherin A in the residues. Graphical
危险品化学品经营许可证（带存储）