Effects of Shenling Baizhu powder on intestinal microflora metabolites and liver mitochondrial energy metabolism in nonalcoholic fatty liver mice

Zheng Yao; Jia Guo; Bing Du; Li Hong; Ying Zhu; Xiaoyi Feng; Yuanlu Hou; Anhua Shi

doi:10.3389/fmicb.2023.1147067

Effects of Shenling Baizhu powder on intestinal microflora metabolites and liver mitochondrial energy metabolism in nonalcoholic fatty liver mice

Front Microbiol. 2023 Jul 18:14:1147067. doi: 10.3389/fmicb.2023.1147067. eCollection 2023.

Authors

Zheng Yao^{1

2

3}, Jia Guo^{1

4}, Bing Du^{1

5}, Li Hong^{1

6}, Ying Zhu¹, Xiaoyi Feng¹, Yuanlu Hou¹, Anhua Shi^{1

2

3}

Affiliations

¹ School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, China.
² The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, China.
³ Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Kunming, China.
⁴ Dongtai City Hospital of Traditional Chinese Medicine, Dongtai, China.
⁵ Heilongjiang Provincial Hospital of Traditional Chinese Medicine, Harbin, China.
⁶ Wuhan Special Service Recuperation Center, Wuhan, China.

Abstract

Background & purpose: Non-alcoholic fatty liver disease (NAFLD) is characterised by the excessive accumulation of triglycerides in the liver. Shenling Baizhu powder (SLBZP) is formulated from various natural medicinal plants that protect the liver and are used to treat intestinal diseases. SLBZP improves the symptoms of NAFLD. However, its mechanism of action remains unclear. Herein, we investigated the ameliorative effect of SLBZP on model mice with high-fat-diet (HFD)-induced NAFLD. Additionally, we evaluated the impact of SLBZP on the intestinal flora and its metabolites and mitochondrial energy metabolism in NAFLD.

Methods: We used HFD to establish a mouse model of NAFLD. Different drug interventions were administered. We measured serum biochemical indices. Liver sections were visualised with hematoxylin-eosin and oil red O staining. 16S rDNA amplicon sequencing technology was used to analyse the diversity and abundance of the intestinal flora. Short-chain fatty acids (SCFAs) in the intestinal contents were detected using GC-MS. Liver tissue was sampled to detect mitochondrial membrane functional indices. Western blotting was used to determine the levels of mitochondrial pathway-related proteins, namely, uncoupling protein 2 (UCP2), adenosine monophosphate-activated protein kinase (AMPK) and inhibitory factor 1 (IF1) of F1Fo ATP synthesis/hydrolase, in the liver.

Results: The spleen-invigorating classic recipe of SLBZP reduced liver lipid deposition in mice with HFD-induced NAFLD. Additionally, SCFAs produced by intestinal flora metabolism regulated the UCP2/AMPK/IF1 signalling pathway involved in liver mitochondrial energy metabolism to improve the liver mitochondrial membrane permeability, respiratory state and oxidative phosphorylation efficiency of mice with NAFLD. Finally, SLBZP increased the liver ATP level.

Conclusion: Our results suggest that the therapeutic effect of SLBZP on NAFLD is related to the regulation of hepatic mitochondrial energy metabolism by intestinal flora and its metabolites and is possibly associated with the UCP2/AMPK/IF1 signalling pathway.

Keywords: AMPK; IF1; NAFLD; Shenling Baizhu powder; UCP2; intestinal flora; mitochondria; short-chain fatty acid.