Joly Raznin, Tasnim Fariha, Krutsinger Kelsey, Li Zhuorui, Pullen Nicholas A, Han Yuyan
College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
Department of Biological Sciences, University of Northern Colorado, Greeley, CO 80639, USA.
Nutrients. 2025 Apr 30;17(9):1524. doi: 10.3390/nu17091524.
Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), involves inflammation, fibrosis, steatosis, and oxidative stress. Previous research from our lab shows that cannabigerol (CBG) reduces inflammation and fibrosis in male MASH mice, but its effects in females remain unknown. Given immune cell population changes in MASLD patients, this study examines CBG's impact on methionine-choline deficient (MCD) diet-induced MASH in female mice. MCD-fed female mice are supplemented with two different doses for three weeks. Liver fibrosis, steatosis, oxidative stress, ductular reaction, and inflammation are assessed via Sirius Red, Oil Red O, immunohistochemistry, and immunofluorescence staining. Immune cell changes in non-parenchymal cells (NPCs) are analyzed via flow cytometry. CBG treatment improves liver health by reducing leukocyte infiltration. Both CBG doses significantly decrease fibrosis, oxidative stress, ductular proliferation, and inflammation in MCD-fed mice, including monocyte and T lymphocyte reductions. Additionally, CBG downregulates mast cell activation, inhibiting transforming growth factor (TGF)-β1 release, thereby suppressing hepatic stellate cell activation. This reduces collagen deposition, fibrosis, and ductular proliferation. Our findings provide insights for pre-clinical and clinical research, highlighting CBG's potential therapeutic role and dosage considerations in mitigating liver fibrosis and inflammation in female patients.
代谢功能障碍相关脂肪性肝炎（MASH）是代谢功能障碍相关脂肪性肝病（MASLD）的一种进行性形式，涉及炎症、纤维化、脂肪变性和氧化应激。我们实验室之前的研究表明，大麻二醇（CBG）可减轻雄性MASH小鼠的炎症和纤维化，但其对雌性小鼠的影响尚不清楚。鉴于MASLD患者免疫细胞群体的变化，本研究考察了CBG对蛋氨酸-胆碱缺乏（MCD）饮食诱导的雌性小鼠MASH的影响。给喂食MCD的雌性小鼠补充两种不同剂量的CBG，持续三周。通过天狼星红、油红O、免疫组织化学和免疫荧光染色评估肝纤维化、脂肪变性、氧化应激、小胆管反应和炎症。通过流式细胞术分析非实质细胞（NPC）中的免疫细胞变化。CBG治疗通过减少白细胞浸润改善肝脏健康。两种CBG剂量均显著降低了喂食MCD小鼠的纤维化、氧化应激、小胆管增殖和炎症，包括单核细胞和T淋巴细胞数量的减少。此外，CBG下调肥大细胞活化，抑制转化生长因子（TGF）-β1释放，从而抑制肝星状细胞活化。这减少了胶原蛋白沉积、纤维化和小胆管增殖。我们的研究结果为临床前和临床研究提供了见解，突出了CBG在减轻女性患者肝纤维化和炎症方面的潜在治疗作用和剂量考量。
