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Chrysanthemum morifolium attenuates metabolic and alcohol-associated liver…

- - - - Status
        
        effective drugs for treating MetALD are lacking
  - - - alcohol abuse induces gut dysbiosis and disruption of the gut barrier
        
        leads to the translocation of pathogenic bacteria and microbial metabolites into the liver
        
        releasing serum endotoxin and inflammatory cytokines, thus inducing liver injury
      - Gut microbial disturbance disrupts metabolic homeostasis, including fatty acid metabolism, which is associated with lipid metabolism in ALD patients
        
        the coexistence of metabolic dysfunction potentiates existing liver injury caused by exogenous alcohol intake by increasing endogenous alcohol-producing microbes
  - - - For example, microbiota-activated PPARγ signaling is critical in maintaining metabolic homeostasis
        
        Short-chain fatty acids（butyrate and propionate） generated via the gut microbiota improve metabolic disorders in mice by regulating PPARγ
        
        reported that ALD induces microbiota disturbance, reducing the co-expression of Fmo5 and PPARα and activating inflammation.
        
        Moreover, gut dysbiosis promotes PPARα deficiency-mediated alcoholic liver injury through the promotion of lipid accumulation, which is a prerequisite for the development of ALD
  - - - Nonetheless, the therapeutic effect of C. morifolium on MetALD and its underlying mechanism remain unclear.
- - - - The chemical constituents of the WECM were analyzed using UPLC-Q-TOF-MS.
    - - HE staining in liver
        
        Serum LDL-C, TC, TG, AST, and ALT
    - - Masson staining of rat thoracic aorta
        
        blood pressure
        
        measured the CRP, ET-1, Ang II and eNOS biochemical markers to assess vascular endothelial function
        
        serum oxidative stress biomarkers(SOD ,MDA GSH-Px) were determined
  - - - 16S rDNA sequencing was conducted with fecal samples to analyze the gut microbiota composition and abundance.
        
        Shannon and Simpson indices of the WECM-M group markedly increased compared with the control group, but the Chao1 index did not significantly change
        
        Principal coordinate analysis
  - - - nontargeted metabolomics analysis
        
        PCA
        
        OPLS-DA
        
        volcano plot
    - - Based on metabolomics and 16S rDNA findings
        
        Serum levels of 15d-PGJ2 , COX-1 , COX-2 , and PTGDS measured using ELISA kits
        
        mRNA expressions of PPARγ assessed by RT-PCR.
        
        protein levels of PPARγ and adiponectin
        
        Serum levels of TNF-α , IL-6 , IL-1β and TGF-β
    - - PPARα mRNA and protein expression