Multi-Omics Integration Analysis Identifies Lipid Disorder of a Non-Alcoholic Fatty Liver Disease (NAFLD) Mouse Model Improved by Zexie–Baizhu Decoction

Abstract

Non-alcoholic fatty liver disease (NAFLD) is an increasingly epidemic metabolic disease with complex pathogenesis. Multi-target therapy may be an effective strategy for NAFLD treatment, and traditional Chinese medicine (TCM) characterized by multi-ingredients and multi-targets has unique advantages in long-term clinical practice. Zexie–Baizhu (ZXBZ) decoction is a Chinese classical formula to treat body fluid disorders initially. Although many bioactive monomers from Zexie and Baizhu had been discovered to improve lipid disorders, limited research studies were focused on the aqueous decoction of ZXBZ, the original clinical formulation. In the current study, we identified 94% chemical composition of ZXBZ decoction and first discovered its hepaprotective effect in a gubra-amylin NASH (GAN) diet-induced NAFLD mouse model. Based on metabolomics and transcriptomics analyses, we speculated that lipid and glucose metabolisms might be regulated by ZXBZ decoction, which was further confirmed by improved dyslipidemia and hepatic steatosis in ZXBZ groups. Consistently with cross-omics analysis, we discovered ZXBZ decoction could influence two energy sensors, Sirt1 and AMPK, and subsequently affect related proteins involved in lipid biosynthesis, catabolism, and transport. In conclusion, ZXBZ decoction regulated energy sensors, consequently impeded lipogenesis, and promoted fatty acid oxidation (FAO) to alleviate lipid disorders and protect the liver in NAFLD models, which suggested ZXBZ decoction might be a promising treatment for NAFLD.

High-performance grating-like SERS substrate based on machine learning for ultrasensitive detection of Zexie-Baizhu decoction

“…Zexie has antiviral [ 1 ], anti-inflammatory [ 2 ] effect and Baizhu also been shown to have antioxidant [ 3 ], inhibit cancer cells value-added role [ 4 ]. The combination of all decoctions has significant effect on the treatment of Nonalcoholic fatty liver disease (NAFLD) [ 5 , 6 ]. We hope that the study will advance the exploitation of ZXBZD, which will bring new enlightenment for modern development of TCM decoctions.…”

Multi-omics reveals that green pea (Pisum sativum L.) hull supplementation ameliorates non-alcoholic fatty liver disease via the SHMT2/glycine/mTOR/PPAR-γ signaling pathway

“…4 However, the pathogenesis of NAFLD is complex, involving oxidative stress, insulin resistance, mitochondrial function, inflammation, gut barrier and gut microbes, [5][6][7] and intervention with single-target drugs may cause adverse reactions and compensatory feedback. 8 Dietary intervention, on the other hand, is a mild, simple and effective alternative treatment because of its multi-component and multi-target characteristics. Instant dark tea was reported to promote fat oxidation and enhance antioxidant activity in the liver of mice fed a HFD.…”

Green Pea (Pisum sativum L.) Hull Polyphenol Extract Alleviates NAFLD through VB6/TLR4/NF-κB and PPAR Pathways

“…NAFLD includes the initial simple fatty liver to nonalcoholic steatohepatitis, and even fibrosis, cirrhosis, and cancer. , As a global health problem, NAFLD affects 20–30% of the population, especially in the obesity group with a 75% incidence rate . Nevertheless, the specific mechanism has not yet been illustrated regarding its pathogenesis from the previously widely accepted “two-hit hypothesis” to the present “multiple parallel hits hypothesis” . Caused by overaccumulation of lipids in liver and insulin resistance, fatty liver and diabetes are regarded as the “first hit”, which can easily trigger the “second hit” that includes oxidative stress, lipid peroxidation, and inflammation .…”

“…3 Nevertheless, the specific mechanism has not yet been illustrated regarding its pathogenesis from the previously widely accepted "two-hit hypothesis" to the present "multiple parallel hits hypothesis". 4 Caused by overaccumulation of lipids in liver and insulin resistance, fatty liver and diabetes are regarded as the "first hit", 5 which can easily trigger the "second hit" that includes oxidative stress, lipid peroxidation, and inflammation. 6 The "multiple parallel hits" is a complex hypothesis involving multiple organs (or tissues) and intestinal flora in NAFLD.…”