Inula britannica ameliorates alcohol-induced liver injury by modulating SIRT1-AMPK/Nrf2/NF-κB signaling pathway

Zhennan Meng; Mengyuan Li; Xiaoli Wang; Kuo Zhang; Chunfu Wu; Xiaoshu Zhang

doi:10.1016/j.chmed.2023.12.006

Inula britannica ameliorates alcohol-induced liver injury by modulating SIRT1-AMPK/Nrf2/NF-κB signaling pathway

Chin Herb Med. 2024 Apr 2;16(4):667-678. doi: 10.1016/j.chmed.2023.12.006. eCollection 2024 Oct.

Authors

Zhennan Meng¹, Mengyuan Li¹, Xiaoli Wang¹, Kuo Zhang², Chunfu Wu², Xiaoshu Zhang¹

Affiliations

¹ Faculity of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China.
² School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

Abstract

Objective: Inula britannica is a traditional Chinese medicinal and functional food with various effects such as anti-liver injury, hypoglycemia, antioxidants, and anti-tumor. The aim of this study was to investigate the protective effects and mechanisms of the ethanolic extract of I. britannica (EEIB) on alcohol-induced liver injury in mice.

Methods: Fifty-six female C57BL/6 mice were randomly divided into seven groups: control group (Con), ethanol feeding model group (EtOH), Silibinin positive treatment group (EtOH + Silibinin 100 mg/kg), EEIB treatment group (EtOH + EEIB 100, 200, and 400 mg/kg), and EEIB control group (EEIB 400 mg/kg). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) ethanol-feeding model was used to study the effects of EEIB on alcohol-induced lipid metabolism, inflammation, oxidative stress, and fibril formation in mice by histopathological evaluation, immunofluorescence staining, Western blotting analysis and molecular docking.

Results: EEIB reduced liver indices to different degrees to normal levels and improved liver morphology in mice. EEIB inhibited alcohol-induced liver injury by activating the sirtuin 1 (SIRT1)-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in the liver of alcohol-fed mice, in which sesquiterpenes may be the potential active ingredients, and also down-regulated the expression of alpha-smooth muscle actin (α-SMA), collagen alpha (Collagen I), tumor necrosis factor-alpha (TNF-α) and attenuated alcohol-induced liver injury. In addition, EEIB also activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which alleviated alcohol-induced liver injury at the level of oxidative stress. Notably, the EEIB control group demonstrated that EEIB had no toxic effects in mice. EEIB reduced alcoholic liver injury in a dose-dependent manner. Its therapeutic efficacy was comparable to, if not better than, that of Silibinin when administered at a dose of 400 mg/kg.

Conclusion: EEIB showed significant therapeutic effects on alcohol-induced liver injury in mice, and its mechanism of action was related to the SIRT1-AMPK, nuclear factor-kappa B (NF-κB), and Nrf2 signaling pathways, in which sesquiterpenes may be the potential active ingredients.

Keywords: Inula britannica L.; SIRT1-AMPK/Nrf2; alcoholic liver injury; inflammation; sesquiterpenes.