Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Zhejiang University, Hangzhou, China.
Eur J Pharmacol. 2016 May 15;779:22-30. doi: 10.1016/j.ejphar.2016.02.067. Epub 2016 Mar 2.
Liver fibrosis is one of the major causes of morbidity and mortality worldwide and lacks efficient therapy. Recent studies suggest the curcumin protects liver from fibrosis. However, curcumin itself is in low bioavailable concentration when administered orally, and the protective mechanism remains poorly understood. The current study aimed to investigate whether a more stable derivative of curcumin, C66, protects against CCl4-inudced liver fibrosis and examine the underlying mechanism involving cannabinoid receptor (CB receptor). At a dose lower than curcumin itself, C66 displayed a superior anti-fibrotic effect. C66 significantly reduced collagen deposition, pro-inflammatory cytokine expression, and liver enzyme activities. Mechanistic study revealed that C66 treatment decreased CCl4-induced cannabinoid receptor 1 (CB1 receptor) expression and increased cannabinoid receptor 2 (CB2 receptor) expression, along with an inhibition of JNK/NF-κB-mediated inflammatory signaling. In conclusion, this curcumin derivative attenuates liver fibrosis likely involving a CB/JNK/NF-κB-mediated pathway.
肝纤维化是全球发病率和死亡率的主要原因之一，目前缺乏有效的治疗方法。最近的研究表明姜黄素可保护肝脏免受纤维化的影响。然而，姜黄素本身经口服给药时生物利用度低，其保护机制仍知之甚少。本研究旨在探讨一种更稳定的姜黄素衍生物 C66 是否可预防 CCl4 诱导的肝纤维化，并研究涉及大麻素受体（CB 受体）的潜在机制。在低于姜黄素本身的剂量下，C66 表现出更好的抗纤维化作用。C66 可显著减少胶原沉积、促炎细胞因子表达和肝酶活性。机制研究表明，C66 治疗可降低 CCl4 诱导的大麻素受体 1（CB1 受体）表达，增加大麻素受体 2（CB2 受体）表达，并抑制 JNK/NF-κB 介导的炎症信号通路。综上所述，这种姜黄素衍生物可减轻肝纤维化，可能涉及 CB/JNK/NF-κB 介导的途径。
