Zexie-Baizhu Decoction ameliorates non-alcoholic fatty liver disease through gut-adipose tissue crosstalk.

J Ethnopharmacol

National Engineering Research Center of TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, China. Electronic address:

Published: January 2025

AI Article Synopsis

  • Zexie-Baizhu Decoction (AA) is a traditional Chinese medicine formula used for metabolic disorders, particularly non-alcoholic fatty liver disease (NAFLD), but its mechanisms on gut and fat tissue are not fully understood.
  • The study aimed to explore how AA impacts gut and adipose tissue homeostasis in the context of NAFLD using various scientific methods, including RNA sequencing and lipidomics.
  • Results showed that AA significantly reduced liver damage and fat accumulation by promoting healthy gut bacteria, restoring bile acid and short-chain fatty acid levels, and activating specific receptors in adipose tissue that help break down fats.

Article Abstract

Ethnopharmacological Relevance: Zexie-Baizhu Decoction (AA), a Chinese Classical Formula composed of Alisma orientalis (Sam.) Juzep. and Aractylodes Macrocephala Koidz in the specific ratio of 5:2, has a long history of use in treating metabolic disorders. Recent studies have demonstrated AA's ameliorative effects on non-alcoholic fatty liver disease (NAFLD); however, the mechanism underlying its action on the gut and adipose tissue, key regulators of metabolism, have not been fully explored.

Aim Of The Study: This study aimed to investigate the mechanisms by which AA regulates the homeostasis of gut and adipose tissue in NAFLD.

Materials And Methods: AA (1500 mg/kg/day) or vehicle was administrated to the high-fat diet-induced and normal chow-fed mice (C57BL/6J). Plasma, the liver, gut microbiota, bile acids, and short-chain fatty acids in the gut, were systematically investigated. RNA sequencing analysis, reverse transcription quantitative real-time PCR, and Western Blotting were performed on the epididymal white adipose tissues (eWAT) to explore AA's influence on NAFLD. Lipidomics of the liver and eWAT were analyzed by liquid chromatography-mass spectrometry and desorption electrospray ionization mass spectrometry imaging.

Results: Our study demonstrated that AA administration effectively alleviated liver injury induced by NAFLD, as evidenced by reduced hepatic fat accumulation and inflammation. Mechanistically, AA modulated the composition of the gut microbiota, promoting the growth of beneficial bacteria such as Akkermansia muciniphila and restoring the balance between Firmicutes and Bacteroidetes. Furthermore, AA regulated the levels of bile acids and short-chain fatty acids in the intestine, plasma, and liver. Correspondingly in the eWAT, AA administration activated bile acid receptor (Gpbar1) and short-chain fatty acid receptor (Ffar2), facilitating lipid breakdown and attenuating triglyceride accumulation. Transcriptome analysis revealed that AA influenced gene expression related to fatty acid metabolism, thermogenesis, insulin resistance, AMPK signaling, and the tricarboxylic acid (TCA) cycle, thereby improving NAFLD at the transcriptional level. Additionally, AA treatment significantly altered the lipid composition in the liver, reducing levels of diacylglycerols, triacylglycerols, phosphatidylserines, and cholesterol esters, while increasing levels of phosphatidic acids, phosphatidylethanolamines, and sphingomyelins.

Conclusion: Our study builds a connection between the gut and adipose tissue to understand the mechanism of AA on alleviating NAFLD, providing new insights into the development of targeted therapies for this condition.

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Source
http://dx.doi.org/10.1016/j.jep.2024.118700DOI Listing

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