Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice

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

Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice

Biomed J. 2024 Apr 25:100731. doi: 10.1016/j.bj.2024.100731. Online ahead of print.

Authors

Shun-Li Kuo¹, Chun-Han Su², Kuei-Hung Lai³, Yu-Chia Chang⁴, Jyh-Sheng You⁵, Hsin-Hsin Peng⁶, Chun-Hong Chen⁷, Chi-Chen Lin⁸, Po-Jen Chen⁹, Tsong-Long Hwan¹⁰

Affiliations

¹ Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan; Division of Chinese Medicine Obstetrics and Gynecology, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan. Electronic address: b9105001@cgmh.org.tw.
² Department of Food Science, College of Human Ecology, Fu Jen Catholic University, New Taipei City, 242062, Taiwan. Electronic address: 154286@mail.fju.edu.tw.
³ Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110301, Taiwan; Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 110301, Taiwan. Electronic address: kueihunglai@tmu.edu.tw.
⁴ Research Center for Chinese Herbal Medicine and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333324, Taiwan. Electronic address: ycchang03@mail.cgust.edu.tw.
⁵ Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Taoyuan 333008, Taoyuan, Taiwan. Electronic address: y0606@mail.cgu.edu.tw.
⁶ Division of Chinese Medicine Obstetrics and Gynecology, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan; Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333323, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan. Electronic address: josephine.peng@mail.cgu.edu.tw.
⁷ Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung 824410, Taiwan. Electronic address: anubis0620@gamil.com.
⁸ Program in Translational Medicine, National Chung-Hsing University, Taichung, 402202, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, 404327, Taiwan; Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan. Electronic address: ed113510@edah.org.tw.
⁹ Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung 824410, Taiwan; Graduate Institute of Medicine, I-Shou University, Kaohsiung 824410, Taiwan. Electronic address: lincc@email.nchu.edu.tw.
¹⁰ Research Center for Chinese Herbal Medicine and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333324, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City 243303, Taiwan; Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan. Electronic address: htl@mail.cgust.edu.tw.

PMID: 38677491
DOI: 10.1016/j.bj.2024.100731

Abstract

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.

Keywords: Guizhi Fulin Wan; antioxidant system; apoptosis; autoimmune hepatitis; inflammation.