Bicyclol

Bicyclol (SY801) is an orally active derivative of the traditional Chinese medicine Schisandra chinensis, which has antiviral, anti-inflammatory, immunomodulatory, antioxidant, anti-steatosis, anti-fibrotic and anti-tumor activities. Bicyclol regulates the expression of heat shock proteins and plays an anti-apoptosis role in hepatocytes. Bicyclol reduces the activation of NF-κB and the levels of inflammatory factors in hepatocytes infected with hepatitis C virus (HCV) by inhibiting the activation of the ROS-MAPK-NF-κB pathway, and prevents ferroptosis in acute liver injury. Bicyclol can change the expression of Mdr-1, GSH/GST and Bcl-2, increase the intracellular concentration of anticancer drugs, and sensitize drug-resistant cells to anticancer drugs. Bicyclol inhibits the proliferation of human malignant hepatoma cells by regulating the PI3K/AKT pathway and the Ras/Raf/MEK/ERK pathway. Bicyclol can be used in the study of chronic hepatitis, acute liver injury, nonalcoholic fatty liver disease, liver fibrosis and hepatocellular carcinoma^{[1][2][3][4][5][6][7][8]}. In Vitro:Bicyclol (0.1-1 mmol/L, 3 h) inhibits the release of ALT and AST, as well as the production of MDA, in CCl₄-induced hepatotoxic Wistar rat hepatocytes in a dose-dependent manner^[1].
Bicyclol (40 and 80 μM; 1 h) reduces palmitic acid (HY-N0830)-induced apoptosis in human hepatocyte HL-7702 cells and inhibits palmitic acid (HY-N0830)-induced activation of MAPKs and NF-κB in macrophages^[2].
Bicyclol (200 μM; 10 h) reduces the level of intracellular oxygen free radicals in HCV-infected Huh7.5 cells and inhibits the phosphorylation of p38, ERK, JNK, and NF-κB^[4].
Bicyclol (10 μM; 30 min) alleviates serrata-induced hepatocyte inactivation, destruction, and lipid peroxidation. Bicyclol (0-500 μM; 0-48 h) effectively inhibits the proliferation of HepG2 cells in a dose-dependent and time-dependent manner^[5].
Bicyclol (0-100 μM; 24 h) reverses vincristine sulfate (HY-N0488) resistance in VinRKB cells by 2.8, 7.3, and 20.7 times, respectively^[6].
Bicyclol (50 and 100 μM; 12-72 h) alters the intracellular drug concentrations in vincristine sulfate (HY-N0488)-resistant human epidermoid carcinoma VinRKB and doxorubicin (HY-15142A)-resistant human breast cancer AdrRMCF-7 cells, sensitizing the resistant cells to anticancer drugs^[8].
In Vivo:Bicyclol (50, 100 and 200 mg/kg; p.o.; single dose) has a dose-dependent protective effect against liver damage induced by different drugs in mice^[1].
Bicyclol (50 and 150 mg/kg; p.o.; once a day for 3 days) has a significant protective effect against Acetaminophen (HY-66005) induced mitochondrial damage in mouse hepatocytes^[1].
Bicyclol (150 mg/kg; p.o.; once a day for 3 days) inhibits the expression of Fas/FasL mRNA and the release of TNF-α in mouse hepatocytes induced by ConA and plays an anti-apoptotic role in hepatocytes^[1].
Bicyclol (300 mg/kg; p.o.; once daily for 3 days) alleviates ConA- and Acetaminophen (HY-66005) induced liver damage in mice, reducing serum transaminases, liver necrosis, mitochondrial cytochrome C and apoptosis-inducing factor (AIF) release, and liver DNA fragmentation^[1].
Bicyclol (75 and 150 mg/kg; p.o.; 6 times per week except Sunday for 7 weeks) significantly improves liver damage and fibrosis in rats and mice induces by chronic CCl4 and Dimethylnitosamine hepatotoxicity^1].
Bicyclol (25 and 50 mg/kg; p.o.; once every other day for 4 weeks) alleviates hyperlipidemia and liver damage and inhibites inflammatory signaling pathways in HFD-induced NAFLD mice^[2].
Bicyclol (200 mg/kg; i.p.; 3 times a day for 2 days) inhibits iron-induced apoptosis in the liver of CCl4-induced ALI mice and exerts a hepatoprotective effect^[5].