2. Academic Validation
  3. Efficacy and mechanism of action of Yanxiao Di'naer formula for non-alcoholic steatohepatitis treatment based on metabolomics and RNA sequencing

Efficacy and mechanism of action of Yanxiao Di'naer formula for non-alcoholic steatohepatitis treatment based on metabolomics and RNA sequencing

  • J Ethnopharmacol. 2024 Oct 28:333:118487. doi: 10.1016/j.jep.2024.118487.
Dong-Xuan Zheng 1,  Qiang Hou 2,  Tao-Tao Xue 3,  Xiang Gao 4,  Ruo-Yu Geng 5,  Li-Mei Wen 6,  Zhi Wang 7,  Qiang Yin 8,  Hai-Long Yin 9,  Jun-Ping Hu 10,  Jian-Hua Yang 11
Affiliations

Affiliations

  • 1 Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, China. Electronic address: zdx15651074992@163.com.
  • 2 Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, China. Electronic address: hq_sci@163.com.
  • 3 Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, China. Electronic address: xtt1221@email.sntcm.edu.cn.
  • 4 Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, China. Electronic address: 17690922658@163.com.
  • 5 Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, China. Electronic address: gryxjmu@163.com.
  • 6 Department of Pharmacy, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China. Electronic address: wendywenlimei@163.com.
  • 7 Department of Pharmacy, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China. Electronic address: wzls913@163.com.
  • 8 Xinjiang Uygur Pharmaceutical Co., LTD., Urumqi, Xinjiang, China. Electronic address: yinqiang@renfu.com.cn.
  • 9 Xinjiang Uygur Pharmaceutical Co., LTD., Urumqi, Xinjiang, China. Electronic address: yinhailong@renfu.com.cn.
  • 10 Department of Pharmacy, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China. Electronic address: hjp-yft@163.com.
  • 11 Department of Pharmacognosy, School of Pharmacy, Xinjiang Medical University, Urumqi, China; Department of Pharmacy, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China. Electronic address: yjh_yfy@163.com.
PMID: 38925322 DOI: 10.1016/j.jep.2024.118487
Abstract

Ethnopharmacological relevance: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear.

Objective: The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms.

Methods: The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro. In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo. Metabolomics and RNA Sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα.

Results: This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA Sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p-NF-κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA.

Conclusions: YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.

Keywords

AMPKα1/pparα/NF-κB pathway; Nonalcoholic steatohepatitis; RNA sequencing; Yanxiao Di'naer formula.

Figures
Products