Phyllanthus emblica aqueous extract retards hepatic steatosis and fibrosis in NAFLD mice in association with the reshaping of intestinal microecology

Luo, Xiaomin; Zhang, Boyu; Pan, Yehua; Gu, Jian; Tan, Rui; Gong, Puyang

doi:10.3389/fphar.2022.893561

Cited by 21 publications

(13 citation statements)

References 62 publications

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“…Similar results were obtained in this study that Muribaculaceae had wide and negative correlations with therapeutic indicators. The abundance of Faecalibaculum is known to be significantly elevated in NAFLD mice, which was consistent with our results ( 56 , 57 ). Positive correlations were also found between Faecalibaculum and most therapeutic indicators.…”

Section: Discussionsupporting

confidence: 93%

Qingrequzhuo capsule alleviated methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice through regulating gut microbiota, enhancing gut tight junction and inhibiting the activation of TLR4/NF-κB signaling pathway

Zhang

et al. 2023

Front. Endocrinol.

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Qingrequzhuo capsule (QRQZ), composed of Morus alba L., Coptis chinensis Franch., Anemarrhena asphodeloides Bunge, Alisma plantago-aquatica subsp. orientale (Sam.) Sam., Citrus × aurantium L., Carthamus tinctorius L., Rheum palmatum L., Smilax glabra Roxb., Dioscorea oppositifolia L., Cyathula officinalis K.C.Kuan, has been used to treat nonalcoholic steatohepatitis (NASH) in clinic. However, the mechanism of QRQZ on NASH remains unclear. Recent studies have found that the dysfunction of gut microbiota could impair the gut barrier and induce the activation of TLR4/NF-kB signaling pathway, and further contribute to the inflammatory response in NASH. Modulating the gut microbiota to reduce inflammation could prevent the progression of NASH. In this study, a mouse model of NASH was generated by methionine and choline deficient diet (MCD) and treated with QRQZ. First, we evaluated the therapeutic effects of QRQZ on liver injury and inflammation in the NASH mice. Second, the changes in the gut microbiota diversity and abundance in each group of mice were measured through 16S rRNA sequencing. Finally, the effects of QRQZ on gut mucosal permeability, endotoxemia, and liver TLR4/NF-kB signaling pathway levels were examined. Our results showed that QRQZ significantly reduced the lipid accumulation in liver and the liver injury in NASH mice. In addition, QRQZ treatment decreased the levels of inflammatory cytokines in liver. 16S rRNA sequencing showed that QRQZ affected the diversity of gut microbiota and a f f e c t e d t h e r e l a t i v e a b u n d a n c e s o f D u b o s i e l l a , Lachnospiraceae_NK4A136_group, and Blautiain NASH mice. Besides, QRQZ could increase the expression of tight junction proteins (zonula occludens-1 and occludin) in gut and decrease the lipopolysaccharide (LPS) level in serum. Western blot results also showed that QRQZ treatment decreased the protein expression ofTLR4, MyD88 and the phosphorylation of IkB and NF-kBp65 and qPCR results showed that QRQZ treatment down-regulated the gene expression of interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a in liver. In conclusion, our study demonstrated that QRQZ could reduce the lipid accumulation and inflammatory response in NASH model mice. The mechanisms of QRQZ on NASH were associated with modulating gut microbiota, thereby inducing the tight junction of gut barrier, reducing the endotoxemia and inhibiting the activation of TLR4/NFkB signaling pathway in liver.

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Section: Discussionsupporting

confidence: 93%

Qingrequzhuo capsule alleviated methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice through regulating gut microbiota, enhancing gut tight junction and inhibiting the activation of TLR4/NF-κB signaling pathway

Zhang

et al. 2023

Front. Endocrinol.

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“…This suggests that Bacteroides plays an important role in alleviating hepatic lipid accumulation in NAFLD mice. Short-chain fatty acids in the gut help protect the integrity of the intestinal barrier, and some studies have claimed that norank_f_ Muribaculaceae is positively correlated with intestinal short-chain fatty acid levels ( 63 , 64 ). In the present study, camel milk and silymarin upregulated the relative abundance of norank_f_ Muribaculaceae in the intestine of NAFLD mice, and we also found that the relative abundance of norank_f_ Muribaculaceae was negatively correlated with serum TG level and liver TG level in the clustering analysis of bacterial genera and physiological indicators, suggesting that norank_f_ Muribaculaceae may regulate the levels of TG in serum and liver by increasing the content of short-chain fatty acids in the intestine.…”

Section: Discussionmentioning

confidence: 99%

Modulatory effect of camel milk on intestinal microbiota of mice with non-alcoholic fatty liver disease

Hao

Liang

et al. 2022

Front. Nutr.

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Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease of life, usually caused by unhealthy diet and lifestyle. Compared to normal individuals, the structure of the intestinal flora of NAFLD patients is altered accordingly. This study investigates the effect of camel milk on the regulation of intestinal flora structure in mice with high-fat diet-induced NAFLD. NAFLD model was established by feeding C57BL/6J mice a high-fat diet for 12 weeks, meanwhile camel milk (3.0 g/kg/d), cow milk (3.0 g/kg/d), and silymarin (200 mg/kg/d) were administered by gavage, respectively. Food intake and changes of physiological indexes in mice were observed and recorded. The 16S rRNA gene V3-V4 region was sequenced and the intestinal flora diversity and gene function were predicted in the colon contents of mice from different group. The results showed that camel milk enhanced glucolipid metabolism by downregulate the levels of blood glucose and triglyceride (TG) in serum, reduced lipid accumulation by downregulate the level of TG in the liver and improved liver tissue structure in NAFLD mice (p < 0.05). Meanwhile, camel milk had a positive modulatory effect on the intestinal flora of NAFLD mice, increasing the relative abundance of beneficial bacteria and decreasing the relative abundance of harmful bacteria in the intestinal flora of NAFLD mice, and silymarin had a similar modulatory effect. At the genus level, camel milk increased the relative abundance of Bacteroides, norank_f_Muribaculaceae and Alloprevotella and decreased the relative abundance of Dubosiella and Coriobacteriaceae_UCG-002 (p < 0.05). Camel milk also enhanced Carbohydrate metabolism, Amino acid metabolism, Energy metabolism, Metabolism of cofactors and vitamins and Lipid metabolism in NAFLD mice, thus reducing the degree of hepatic lipid accumulation in NAFLD mice and maintaining the normal structure of the liver. In conclusion, camel milk can improve the structure and diversity of intestinal flora and enhance the levels of substance and energy metabolism in NAFLD mice, which has a positive effect on alleviating NAFLD and improving the structure of intestinal flora.

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“…The resulting precipitate was lyophilized and the high-molecular weight fraction of AEPE (termed HWPE) was obtained. In our previous studies, the main chemical ingredients in AEPE were quantified by high-performance liquid chromatography (HPLC) and the content of crude polysaccharides in HWPE was determined by phenol-sulfuric acid method ( Yin et al, 2021 ; Luo et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…The AEPE and its fractions samples were prepared using the same batch of dried PE fruit (voucher specimens no. 20201212) as in our previous study (Yin et al, 2021;Luo et al, 2022). Briefly, 2000 g of PE was powdered and immersed in distilled water on a rotary shaker for 24 h at a mass ratio of 1:10 at 37 °C.…”

Section: Preparation Of Test Drugsmentioning

confidence: 99%

Tandem mass tag-based proteomics analysis reveals the multitarget mechanisms of Phyllanthus emblica against liver fibrosis

et al. 2022

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Phyllanthus emblica (PE), a traditional multiethnic herbal medicine, is commonly applied to treat liver diseases. Our previous study demonstrated that aqueous extract of PE (AEPE) could alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in vivo, but the underlying molecular mechanisms are still unclear. The present study was undertaken to clarify the multitarget mechanisms of PE in treating liver fibrosis by proteomics clues. A CCl4-induced liver fibrosis rat model was established. The anti-liver fibrosis effects of chemical fractions from AEPE were evaluated by serum biochemical indicators and pathological staining. Additionally, tandem mass tag (TMT) - based quantitative proteomics technology was used to detect the hepatic differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, gene ontology (GO) enrichment and protein-protein interaction (PPI) network were used to perform bioinformatics analysis of DEPs. Western blot analysis was used to verify the key potential targets regulated by the effective fraction of AEPE. The low-molecular-weight fraction of AEPE (LWPE) was determined to be the optimal anti-liver fibrosis active fraction, that could significantly improve ALT, AST, HA, Col IV, PCIII, LN, Hyp levels and reduce the pathological fibrotic lesion of liver tissue in model rats. A total of 195 DEPs were screened after LWPE intervention. GO analysis showed that the DEPs were related mostly to extracellular matrix organization, actin binding, and extracellular exosomes. KEGG pathway analysis showed that DEPs are mainly related to ECM-receptor interactions, focal adhesion and PI3K-Akt signaling pathway. Combined with the GO, KEGG and Western blot results, COL1A2, ITGAV, TLR2, ACE, and PDGFRB may be potential targets for PE treatment of liver fibrosis. In conclusion, LWPE exerts therapeutic effects through multiple pathways and multiple targets regulation in the treatment of liver fibrosis. This study may provide proteomics clues for the continuation of research on liver fibrosis treatment with PE.

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Phyllanthus emblica aqueous extract retards hepatic steatosis and fibrosis in NAFLD mice in association with the reshaping of intestinal microecology

Cited by 21 publications

References 62 publications

Qingrequzhuo capsule alleviated methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice through regulating gut microbiota, enhancing gut tight junction and inhibiting the activation of TLR4/NF-κB signaling pathway

Qingrequzhuo capsule alleviated methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice through regulating gut microbiota, enhancing gut tight junction and inhibiting the activation of TLR4/NF-κB signaling pathway

Modulatory effect of camel milk on intestinal microbiota of mice with non-alcoholic fatty liver disease

Tandem mass tag-based proteomics analysis reveals the multitarget mechanisms of Phyllanthus emblica against liver fibrosis

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