Geniposide dosage and administration time: Balancing therapeutic benefits and adverse reactions in liver disease treatment.

Autor: Qiu J; School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, China; E-institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Lin C; School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, China., Ren G; School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, China., Xu F; School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, China., Hu T; Department of Ultrasonography, Chinese PLA 903rd Hospital, Hangzhou 310013, China., Le Y; School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, China., Fan X; Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Yu Z; Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China., Liu Q; Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, Hangzhou, Zhejiang 310000, China., Wang X; E-institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: wxntcm@126.com., Dou X; School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, China. Electronic address: xbdou77@gmail.com.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Sep; Vol. 132, pp. 155799. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1016/j.phymed.2024.155799
Abstrakt: Gardenia jasminoides Ellis, a staple in herbal medicine, has long been esteemed for its purported hepatoprotective properties. Its primary bioactive constituent, geniposide, has attracted considerable scientific interest owing to its multifaceted therapeutic benefits across various health conditions. However, recent investigations have unveiled potential adverse effects associated with its metabolite, genipin, particularly at higher doses and prolonged durations of administration, leading to hepatic injury. Determining the optimal dosage and duration of geniposide administration while elucidating its pharmacological and toxicological mechanisms is imperative for safe and effective clinical application. This study aimed to evaluate the safe dosage and administration duration of geniposide in mice and investigate its toxicological mechanisms within a comprehensive dosage-duration-efficacy/toxicity model. Four distinct mouse models were employed, including wild-type mice, cholestasis-induced mice, globally farnesoid X-activated receptor (FXR) knock out mice, and high-fat diet-induced (HFD) NAFLD mice. Various administration protocols, spanning one or four weeks and comprising two or three oral doses, were tailored to each model's requirements. Geniposide has positive effects on bile acid and lipid metabolism at doses below 220 mg/kg/day without causing liver injury in normal mice. However, in mice with NAFLD, this dosage is less effective in improving liver function, lipid profiles, and bile acid metabolism compared to lower doses. In cholestasis-induced mice, prolonged use of geniposide at 220 mg/kg/day worsened liver damage. Additionally, in NAFLD mice, this dosage of geniposide for four weeks led to intestinal pyroptosis and liver inflammation. These results highlight the lipid-lowering and bile acid regulatory effects of geniposide, but also warn of potential negative impacts on intestinal epithelial cells, particularly with higher doses and longer treatment durations. Therefore, achieving optimal therapeutic results requires a decrease in treatment duration as the dosage increases, in order to maintain a balanced approach to the use of geniposide in clinical settings.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier GmbH.)
Databáze: MEDLINE
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