Kuo Shun-Li, Su Chun-Han, Lai Kuei-Hung, Chang Yu-Chia, You Jyh-Sheng, Peng Hsin-Hsin, Chen Chun-Hong, Lin Chi-Chen, Chen Po-Jen, Hwang Tsong-Long
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Chinese Medicine Obstetrics and Gynecology, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Food Science, College of Human Ecology, Fu Jen Catholic University, New Taipei City, Taiwan.
Biomed J. 2025 Feb;48(1):100731. doi: 10.1016/j.bj.2024.100731. Epub 2024 Apr 26.
Autoimmune hepatitis (AIH) is an immune-mediated hepatic disease associated with intense complications. AIH is more common in females and needs effective drugs to treat. Guizhi Fuling Wan (GZFLW) is a traditional Chinese herbal formula for treating various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH.
The tandem MS-based analysis was used to identify secondary metabolites in GZFLW. Therapeutic effects of GZFLW were tested in a concanavalin A (Con A)-induced AIH model in mice. Ethnopharmacological mechanisms underlying the antiapoptotic, antioxidant, and immunomodulatory protective effects were determined.
Oral administration of GZFLW attenuates AIH in a Con A-induced hepatotoxic model in vivo. The tandem MS-based analysis identified 15 secondary metabolites in GZFLW. The Con A-induced AIH syndromes, including hepatic apoptosis, inflammation, reactive oxygen species accumulation, function failure, and mortality, were significantly alleviated by GZFLW in mice. Mechanistically, GZFLW restrained the caspase-dependent apoptosis, restored the antioxidant system, and decreased pro-inflammatory cytokine production in the livers of Con A-treated mice. Besides, GZFLW repressed the Con A-induced hepatic infiltration of inflammatory cells, splenic T cell activation, and splenomegaly in mice.
Our findings demonstrate the applicable potential of GZFLW in treating AIH. It prompts further investigation of GZFLW as a treatment option for AIH and possibly other hepatic diseases.
自身免疫性肝炎(AIH)是一种与严重并发症相关的免疫介导性肝病。AIH在女性中更为常见,需要有效的药物进行治疗。桂枝茯苓丸(GZFLW)是一种用于治疗各种妇科疾病的传统中药配方。在本研究中,我们旨在拓展GZFLW在AIH治疗方面的新用途。
采用基于串联质谱的分析方法来鉴定GZFLW中的次生代谢产物。在刀豆蛋白A(Con A)诱导的小鼠AIH模型中测试GZFLW的治疗效果。确定其抗凋亡、抗氧化和免疫调节保护作用背后的民族药理学机制。
口服GZFLW可减轻体内Con A诱导的肝毒性模型中的AIH。基于串联质谱的分析鉴定出GZFLW中的15种次生代谢产物。GZFLW可显著减轻Con A诱导的AIH综合征,包括肝细胞凋亡、炎症、活性氧积累、功能衰竭和死亡率。从机制上讲,GZFLW抑制了半胱天冬酶依赖性凋亡,恢复了抗氧化系统,并减少了Con A处理小鼠肝脏中促炎细胞因子的产生。此外,GZFLW还抑制了Con A诱导的小鼠肝脏炎症细胞浸润、脾T细胞活化和脾肿大。
我们的研究结果证明了GZFLW在治疗AIH方面的应用潜力。这促使进一步研究将GZFLW作为AIH及可能的其他肝病的治疗选择。