Bader Eddin Lujain, Mahgoub Amar, Almarzooqi Saeeda, Adeghate Ernest, Subramanya Sandeep B, Ojha Shreesh
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.
Int J Mol Sci. 2025 Sep 1;26(17):8493. doi: 10.3390/ijms26178493.
Liver fibrosis is associated with increased rates of morbidity and mortality. At present, there are no specific treatments that can directly reverse hepatic fibrosis. The endocannabinoid system has been found to play a significant role in regulating the development and progression of liver diseases, in addition to having protective effects. In this study, we investigate the protective potential of β-Caryophyllene (BCP) against Thioacetamide (TAA)-induced liver fibrosis. Wistar rats were injected with TAA (200 mg/kg) three times per week for 8 weeks to induce liver fibrosis. They also received oral BCP before the TAA injections. AM630 (1 mg/kg) was administered to confirm the CB2 receptor-dependent effect of BCP. The BCP treatment (50 mg/kg) protected against cell injury and potentiated antioxidant defense by replenishing hepatic GSH, improving catalase activity, and inhibiting the formation of MDA. The co-administration of BCP mitigated the TAA-induced inflammatory response by decreasing the release of proinflammatory cytokines. Histological examination showed preserved cellular integrity, decreased collagen deposits with other extracellular matrix proteins, and low levels of myofibroblast activation. In addition, the BCP-treated rats demonstrated upregulated sirtuin 1 (SIRT1) expression, which had a direct inhibitory effect on hypoxia inducible factor (HIF-1α). AM630 pre-treatment inhibited all the aforementioned protective mechanisms of BCP. Based on our findings, BCP exerts protective effects in liver fibrosis, which can be attributed to its agonist action on CB2 receptors. This study provides preclinical evidence of the potential preventative benefits of BCP in liver fibrosis.
肝纤维化与发病率和死亡率的增加相关。目前，尚无能够直接逆转肝纤维化的特异性治疗方法。除了具有保护作用外，内源性大麻素系统已被发现参与调节肝脏疾病的发生发展。在本研究中，我们探究了β-石竹烯（BCP）对硫代乙酰胺（TAA）诱导的肝纤维化的保护潜力。将Wistar大鼠每周注射3次TAA（200mg/kg），持续8周以诱导肝纤维化。在注射TAA之前，它们还接受了口服BCP。给予AM630（1mg/kg）以证实BCP的CB2受体依赖性作用。BCP治疗（50mg/kg）通过补充肝脏谷胱甘肽、提高过氧化氢酶活性和抑制丙二醛的形成来保护细胞免受损伤并增强抗氧化防御。BCP的联合给药通过减少促炎细胞因子的释放减轻了TAA诱导的炎症反应。组织学检查显示细胞完整性得以保留，胶原沉积与其他细胞外基质蛋白减少，肌成纤维细胞活化水平较低。此外，BCP处理的大鼠显示沉默调节蛋白1（SIRT1）表达上调，其对缺氧诱导因子（HIF-1α）具有直接抑制作用。AM630预处理抑制了BCP的所有上述保护机制。基于我们的研究结果，BCP在肝纤维化中发挥保护作用，这可归因于其对CB2受体的激动作用。本研究为BCP在肝纤维化中潜在的预防益处提供了临床前证据。
