ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
This article is part of the Research TopicRodent Model Organisms: Therapeutic Treatments and Drugs Interaction with the Gut Microbiome, Volume IIView all 18 articles
Hesperidin Alleviated D-GalN/LPS Induced Acute Liver Injury in Mice: Insights into Gut Microbiota and the Nrf2/Keap1 Pathway
Provisionally accepted
- 1Nanjing University of Chinese Medicine, Nanjing, China
- 2Southeast University, Nanjing, China
- 3Department of Critical Care Medicine, Affiliated Jinling Hospital, Nanjing University, Nanjing, China
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Plant extracts of natural origin can regulate the composition of intestinal flora through the "gut-liver axis" pathway, potentially ameliorating acute liver injury (ALI). Hesperidin (HDN), a flavonoid with protective liver bioactivity, was examined in this work for its possible use in treating and preventing D-GalN/LPS-induced ALI in mice. The aim of this research was to explore the beneficial effects of Hesperidin to prevent D-GalN/LPS-induced acute liver injury and elaborate on its hepatoprotective mechanisms. The results showed that Hesperidin significantly ameliorated D-GalN/LPS-induced abnormal transaminase activities, liver and intestinal systemic inflammation, and intestinal environmental disorders. Furthermore, inhibition of the Nrf2/keap1 signal pathway by HDN reduced the production of proinflammatory cytokines (TNF-α, IL-1β and IL-6) and boost the activity of antioxidant enzymes (CAT and SOD). HDN restored SCFAs to normal levels by upregulating the abundance of beneficial bacteria (Lachnospiraceae_NK4A136_group Alloprevotella and Clostridia_UCG-014). The alleviation of ALI by HDN occurs through protection of the intestinal mucosal barrier and reduction of LPS permeating in serum. The decrease in LPS inactivates the Nrf2/keap1 signaling pathway and prevents inflammation. In short, HDN regulates the gut−liver axis, oxidative stress, inflammation, alleviating effects in ALI mice.
Keywords: Hesperidin, Acute liver injury, Gut Microbiota, Gut-liver axis, Nrf2/Keap1 signaling pathway
Received: 15 Oct 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Li, Hou, Deng, Lu, Liu, Wang, Tong and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qi Wang
Zhihui Tong
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