Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, China.
Exp Biol Med (Maywood). 2024 Apr 22;249:10141. doi: 10.3389/ebm.2024.10141. eCollection 2024.
Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.
肝纤维化已成为严重的公共卫生问题，可发展为肝硬化和肝细胞癌，甚至导致死亡。大麻植物中丰富的非精神活性成分大麻二酚（CBD）在许多疾病和病理条件下发挥细胞保护作用。在我们之前的研究中，CBD 显著减轻了慢性和 binge 酒精诱导的小鼠模型中的肝损伤和人中性粒细胞中的氧化爆发。然而，CBD 对肝纤维化的作用及其潜在机制仍需要进一步研究。用四氯化碳（CCl）诱导小鼠肝纤维化模型 10 周，以探讨 CBD 的保护特性及相关分子机制。注射方案后，使用血清样本和肝脏进行分子生物学、生化和病理分析。结果表明，CBD 可有效改善肝功能，减轻小鼠肝损伤和肝纤维化进展；降低转氨酶和纤维化标志物的表达水平，改善组织病理学特征。此外，CBD 抑制炎症细胞因子水平，降低 p-NF-κB、NF-κB、p-IκBα、p-p38 MAPK 和 COX-2 的蛋白表达水平，增加 PPAR-α 的表达水平。我们发现，CBD 介导的保护作用涉及抑制 NF-κB 并激活 PPAR-α。总之，这些结果表明，CBD 的肝保护作用可能是由于抑制 CCl 诱导的小鼠中的炎症反应，而 NF-κB 和 PPAR-α 信号通路可能参与这一过程。
