CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Key Laboratory of Biotechnology of Antibiotics, The National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Biomed Pharmacother. 2022 Jun;150:113083. doi: 10.1016/j.biopha.2022.113083. Epub 2022 May 10.
Bicyclol, a synthetic hepatoprotective and anti-inflammatory agent approved in China, was widely used to treat various hepatitis accompanied by elevated serum aminotransferases. However, the pharmacological effects and mechanisms of bicyclol on advanced liver diseases, such as fibrosis/cirrhosis and hepatocellular carcinoma (HCC), remain to be explored. Here, we revealed that bicyclol prevents from formatting severe fibrosis, slows the progression of moderate liver fibrosis, accelerates the regression of moderate liver fibrosis, decreases the malignancy of HCC in rat models induced by diethylnitrosamine (DEN), and also blocks steatohepatitis to HCC in mice induced by western diet plus carbon tetrachloride and DEN. The detailed pharmacological mechanism showed that bicyclol alleviates chronic progressive liver diseases by inhibiting the levels of IL-6 and subsequent phosphorylated STAT3. Conclusion: Bicyclol plays significant protective roles in multiply stages of fibrosis/cirrhosis-HCC and nonalcoholic fatty liver disease-related HCC via inhibiting IL-6/STAT3 signaling pathway. Therefore, bicyclol might be a promising therapeutic strategy for treating advanced liver diseases.
双环醇是一种已在中国获批的合成护肝及抗炎药物，广泛用于治疗伴有血清转氨酶升高的各种肝炎。然而，双环醇在纤维化/肝硬化和肝细胞癌（HCC）等晚期肝病中的药理作用和机制仍有待探索。在这里，我们揭示了双环醇可预防严重纤维化形成，减缓中度肝纤维化的进展，加速中度肝纤维化的消退，降低二乙基亚硝胺（DEN）诱导的大鼠模型中 HCC 的恶性程度，还可阻断由西方饮食加四氯化碳和 DEN 诱导的小鼠脂肪性肝炎向 HCC 的进展。详细的药理机制表明，双环醇通过抑制 IL-6 及其后续磷酸化 STAT3 的水平来缓解慢性进行性肝病。结论：双环醇通过抑制 IL-6/STAT3 信号通路，在纤维化/肝硬化-HCC 的多个阶段和非酒精性脂肪性肝病相关 HCC 中发挥显著的保护作用。因此，双环醇可能是治疗晚期肝病的一种有前途的治疗策略。
