Research Article Details

Article ID: A02709
PMID: 34276380
Source: Front Pharmacol
Title: Chlorogenic Acid Improves NAFLD by Regulating gut Microbiota and GLP-1.
Abstract: Our previous studies have shown that chlorogenic acid (CGA) could significantly improve acute and chronic liver injury through antioxidant and anti-inflammatory activities. However, its effect on non-alcoholic fatty liver disease (NAFLD) are not entirely clear. This study aims to explore the effect of CGA on NAFLD induced by high-fat diet (HFD) and whether it regulates the gut microbiota and Glucagon-like peptide-1 (GLP-1). NAFLD mice were established by HFD and treated with or without CGA. Serum transaminase, fasting blood glucose (FBG), blood lipids, insulin, GLP-1 and lipopolysaccharide (LPS) were detected. Liver histology was evaluated with Hematoxylin-eosin staining. Toll like receptor 4 (TLR4) signaling pathway was analyzed with western blot and inflammatory cytokines were detected with real-time PCR. The content of gut microbiota were determined with real-time PCR of the bacterial 16S rRNA gene. Expressions of intestine tight junctional protein were examined with immunohistochemistry. CGA could alleviate HFD-induced hepatic steatosis and inflammation, reduce serum transaminase, FBG and blood lipids, increase insulin sensitivity. CGA also could reverse HFD-induced activation of TLR4 signaling pathway and expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver. Meanwhile, CGA increased the content of Bifidobacterium and reduced the content of Escherichia coli in feces. Furthermore, CGA could increase the expression of tight junction proteins Occludin and zonula occludens-1 (ZO-1) in intestinal tissue. Moreover, CGA could the level of LPS and increased the level of GLP-1 in portal vein. These results indicated that CGA protected against HFD-induced hepatic steatosis and inflammation probably through its anti-inflammatory effects associated with regulation of gut microbiota and an increase of GLP-1 secretion and thus could be used as a potential drug for prevention and treatment of NAFLD.
DOI: 10.3389/fphar.2021.693048

Strategy ID Therapy Strategy Synonyms Therapy Targets Therapy Drugs
S05 Anti-inflammatory inflammatory Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; Details
S06 Regulating intestinal flora intestine gut microbiota; gut microbiota farnesoid X receptor (FXR); fibroblast growth factor-19 (FGF19) Probiotics; Prebiotics; Rifaximin; Yaq-001; Cilofexor; EDP-305; EYP001a; INT-767 Details

Target ID Target Name GENE Action Class UniProtKB ID Entry Name
T06 Glucagon-like peptide 1 receptor GLP1R agonist GPCR P43220 GLP1R_HUMAN Details
T08 Tumor necrosis factor TNF inhibitor Cytokine P01375 TNFA_HUMAN Details
T09 Toll-like receptor 4 TLR4 antagonist Membrane receptor O00206 TLR4_HUMAN Details
T10 Caspase-1 CASP1 inhibitor Enzyme P29466 CASP1_HUMAN Details
T18 Acetyl-CoA carboxylase 1 ACACA inhibitor Enzyme Q13085 ACACA_HUMAN Details
T20 Fatty acid synthase FASN inhibitor Enzyme P49327 FAS_HUMAN Details

Diseases ID DO ID Disease Name Definition Class

Drug ID Drug Name Type DrugBank ID Targets Category Latest Progress
D328 Serine Chemical drug DB00133 SRR Improve insulin resistance Under clinical trials Details
D182 Insulin Biological drug DB00030 INSR agonist; CPE modulator&product of -- Under clinical trials Details
D155 Glucagon Biological drug DB00040 GCGR agonist Antidiabetic drug Under clinical trials Details
D316 S-adenosyl-L-methionine Chemical drug DB00118 GNMT cofactor Antiviral Under clinical trials Details
D094 Cysteamine Chemical drug DB00847 GSS stimulant Renal drug Under clinical trials Details
D095 Cysteamine bitartrate Chemical drug DB00847 -- -- Under clinical trials Details