Curdione and Schisandrin C Synergistically Reverse Hepatic Fibrosis via Modulating the TGF-β Pathway and Inhibiting Oxidative Stress

Abstract

Hepatic fibrosis is the final pathway of several chronic liver diseases, which is characterized by the accumulation of extracellular matrix due to chronic hepatocyte damage. Activation of hepatic stellate cells and oxidative stress (OS) play an important role in mediating liver damage and initiating hepatic fibrosis. Hence, hepatic fibrosis can be reversed by inhibiting multiple channels such as oxidative stress, liver cell damage, or activation of hepatic stellate cells. Liuwei Wuling Tablets is a traditional Chinese medicine formula with the effect of anti- hepatic fibrosis, but the composition and mechanism of reversing hepatic fibrosis are still unclear. Our study demonstrated that one of the main active components of the Chinese medicine Schisandra chinensis, schisandrin C (Sin C), significantly inhibited oxidative stress and prevented hepatocyte injury. Meanwhile one of the main active components of the Chinese medicine Curdione inhibited hepatic stellate cell activation by targeting the TGF-β1/Smads signaling pathway. The further in vivo experiments showed that Sin C, Curdione and the combination of both have the effect of reversing liver fibrosis in mice, and the combined effect of inhibiting hepatic fibrosis is superior to treatment with Sin C or Curdione alone. Our study provides a potential candidate for multi-molecular or multi-pathway combination therapies for the treatment of hepatic fibrosis and demonstrates that combined pharmacotherapy holds great promise in the prevention and treatment of hepatic fibrosis.

A Review of Extraction and Purification, Biological Properties, Structure–Activity Relationships and Future Prospects of Schisandrin C: A Major Active Constituent of Schisandra Chinensis

“…showed that Sch C and the combination of both with Curdione had the effect of reversing liver fibrosis in mice. [57] It is found that Sch C inhibited LPS-induced inflammatory responses in mouse macrophages (Raw 264.7 cells). The inhibitory effect is presumed to be caused by blocking the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1 and 2 (ERK 1/2), and c-Jun N-terminal kinase (JNK).…”

“…It was shown that Sch C significantly inhibited oxidative stress while suppressing hepatic stellate cell activation and preventing hepatocyte injury by targeting the TGF‐ β 1/Smads signaling pathway. Further, in vivo, experiments showed that Sch C and the combination of both with Curdione had the effect of reversing liver fibrosis in mice [57] …”

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

“…Brevilin A [270] Curdione [271] Limonin [272] Piperlongumine, [273] Conophylline [274] Apigenin [224] Salvianolic acid B [216] Taxifolin [275] Paeonol [252] Pterostilbene [276] Sesamol [277] Chelerythrine [278] Physalin D [231] Methoxyeugenol [226] Apigenin [227] Dihydromyricetin (DHM)…”

“…Apart from the above-mentioned natural products targeting HSC, natural products involved in the following related mechanisms: (1) Intervening in the TGFβ/Smad signaling pathway. The natural products involved are: Tanshinone IIA [225] , Protocatechuic acid [265] , Byakangelicin [266] , Quercetin [267] , Gooseberry anthocyanins [268] , Naringenin (NIN) [198] , Germacrone [269] , Brevilin A [270] , Curdione [271] , Limonin [272] , Piperlongumine [273] , Conophylline [274] , Apigenin [227] , Sal-B [219] , Taxifolin [275] , Vanillin [275] , Pterostilbene [276] , Sesamol [277] , Chelerythrine [278] , Physalin D [234] . (2) Reduced HSC activation by activating PPAR-g: Methoxyeugenol [226] , Apigenin [227] .…”

Inhibitory effects of Schisandrin C on collagen behavior in pulmonary fibrosis

“…Schisandrin C (Sch C), one of the lignans of Schisandra Chinese, has been shown to inhibit the TGF-β 1 /Smad2/3 signaling pathway which plays an important role in ECM deposition 4 , 23 . Thus, we hypothesized that Sch C might play a beneficial role in the diminishment of ECM deposition by inhibiting LOX expression contributing to ameliorating PF.…”