2. Academic Validation
  3. Oral administration of astilbin mitigates acetaminophen-induced acute liver injury in mice by modulating the gut microbiota

Oral administration of astilbin mitigates acetaminophen-induced acute liver injury in mice by modulating the gut microbiota

  • Acta Pharmacol Sin. 2024 Sep 23. doi: 10.1038/s41401-024-01383-9.
Qin Yang 1 2,  Wen-Hao He 2,  Li Xie 2,  Tao Chen 3,  Ruo-Fan Liu 2,  Jia-Jia Hu 2,  Jia-Yin Guo 4,  Guo-Zhu Tan 1 5,  Fu-Ling Wu 6,  Peng Gu 7,  Peng Chen 8,  Yu Chen 9
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The Seventh Affiliated Hospital of Southern Medical University, Foshan, 528244, China.
  • 2 Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 3 Department of Physiology, School of Basic Medical Sciences, Gannan Medical University, Ganzhou, 341000, China.
  • 4 Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 5 Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, China.
  • 6 Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • 7 Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. kupper@smu.edu.cn.
  • 8 Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. perchen@smu.edu.cn.
  • 9 Department of Gastroenterology, The Seventh Affiliated Hospital of Southern Medical University, Foshan, 528244, China. askasky@126.com.
PMID: 39313515 DOI: 10.1038/s41401-024-01383-9
Abstract

Acetaminophen (APAP) overdose-induced acute liver injury (ALI) is characterized by extensive oxidative stress, and the clinical interventions for this adverse effect remain limited. Astilbin is an active compound found in the rhizome of Smilax glabra Roxb. with anti-inflammatory and antioxidant activities. Due to its low oral bioavailability, astilbin can accumulate in the intestine, which provides a basis for the interaction between astilbin and gut microbiota (GM). In the present study we investigated the protective effects of astilbin against APAP-induced ALI by focusing on the interaction between astilbin and GM. Mice were treated with astilbin (50 mg·kg-1·d-1, i.g.) for 7 days. After the last administration of astilbin for 2 h, the mice received APAP (300 mg/kg, i.g.) to induce ALI. We showed that oral administration of astilbin significantly alleviated APAP-induced ALI by altering the composition of GM and enriching beneficial metabolites including hydroxytyrosol (HT). GM depletion using an "antibiotics cocktail" or paraoral administration of astilbin abolished the hepatoprotective effects of astilbin. On the Other hand, administration of HT (10 mg/kg, i.g.) caused similar protective effects in APAP-induced ALI mice. Transcriptomic analysis of the liver tissue revealed that HT inhibited Reactive Oxygen Species and inflammation-related signaling in APAP-induced ALI; HT promoted activation of the Nrf2 signaling pathway to combat oxidative stress following APAP challenge in a sirtuin-6-dependent manner. These results highlight that oral astilbin ameliorates APAP-induced ALI by manipulating the GM and metabolites towards a more favorable profile, and provide an alternative therapeutic strategy for alleviating APAP-induced ALI.

Keywords

Sirt6; acetaminophen; acute liver injury; astilbin; gut microbiota; hydroxytyrosol.

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