{"title":"桂枝茯苓丸可改善小鼠由金刚烷胺 A 引起的自身免疫性肝炎。","authors":"Shun-Li Kuo, Chun-Han Su, Kuei-Hung Lai, Yu-Chia Chang, Jyh-Sheng You, Hsin-Hsin Peng, Chun-Hong Chen, Chi-Chen Lin, Po-Jen Chen, Tsong-Long Hwan","doi":"10.1016/j.bj.2024.100731","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 used to treat various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100731"},"PeriodicalIF":4.1000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice.\",\"authors\":\"Shun-Li Kuo, Chun-Han Su, Kuei-Hung Lai, Yu-Chia Chang, Jyh-Sheng You, Hsin-Hsin Peng, Chun-Hong Chen, Chi-Chen Lin, Po-Jen Chen, Tsong-Long Hwan\",\"doi\":\"10.1016/j.bj.2024.100731\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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 used to treat various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Our findings demonstrate the applicable potential of GZFLW in treating AIH. 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引用次数: 0
摘要
背景:自身免疫性肝炎(AIH)是一种免疫介导的肝病,伴有严重的并发症。自身免疫性肝炎多见于女性,需要有效的药物来治疗。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。本研究旨在拓展桂枝茯苓丸治疗 AIH 的新用途:方法:采用串联质谱分析法鉴定 GZFLW 中的次生代谢物。方法:采用串联质谱分析法鉴定了 GZFLW 中的次生代谢物,并在小鼠由 Con A 诱导的 AIH 模型中测试了 GZFLW 的治疗效果。确定了抗细胞凋亡、抗氧化和免疫调节保护作用的民族药理学机制:结果:在 Con A 诱导的体内肝毒性模型中,口服 GZFLW 可减轻 AIH。基于串联质谱的分析确定了 GZFLW 中的 15 种次生代谢物。GZFLW 能显著缓解 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。从机理上讲,GZFLW抑制了Caspase依赖性细胞凋亡,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还能抑制Con A诱导的小鼠肝脏炎症细胞浸润、脾脏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。结论:我们的研究结果表明了 GZFLW 在治疗 AIH 方面的应用潜力,这也促使我们进一步研究 GZFLW 作为 AIH 及其他肝病治疗方法的可能性。
Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice.
Background: 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 used to treat various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍:
Biomedical Journal publishes 6 peer-reviewed issues per year in all fields of clinical and biomedical sciences for an internationally diverse authorship. Unlike most open access journals, which are free to readers but not authors, Biomedical Journal does not charge for subscription, submission, processing or publication of manuscripts, nor for color reproduction of photographs.
Clinical studies, accounts of clinical trials, biomarker studies, and characterization of human pathogens are within the scope of the journal, as well as basic studies in model species such as Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealing the function of molecules, cells, and tissues relevant for human health. However, articles on other species can be published if they contribute to our understanding of basic mechanisms of biology.
A highly-cited international editorial board assures timely publication of manuscripts. Reviews on recent progress in biomedical sciences are commissioned by the editors.