The seamless integration of dietary plant-derived natural flavonoids and gut microbiota may ameliorate non-alcoholic fatty liver disease: a network pharmacology analysis

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):217-232. doi: 10.1080/21691401.2023.2203734.


We comprised metabolites of gut microbiota (GM; endogenous species) and dietary plant-derived natural flavonoids (DPDNFs; exogenous species) were known as potent effectors against non-alcoholic fatty liver disease (NAFLD) via network pharmacology (NP). The crucial targets against NAFLD were identified via GM and DPDNFs. The protein interaction (PPI), bubble chart and networks of GM or natural products- metabolites-targets-key signalling (GNMTK) pathway were described via R Package. Furthermore, the molecular docking test (MDT) to verify the affinity was performed between metabolite(s) and target(s) on a key signalling pathway. On the networks of GNMTK, Enterococcus sp. 45, Escherichia sp.12, Escherichia sp.33 and Bacterium MRG-PMF-1 as key microbiota; flavonoid-rich products as key natural resources; luteolin and myricetin as key metabolites (or dietary flavonoids); AKT Serine/Threonine Kinase 1 (AKT1), CF Transmembrane conductance Regulator (CFTR) and PhosphoInositide-3-Kinase, Regulatory subunit 1 (PIK3R1) as key targets are promising components to treat NAFLD, by suppressing cyclic Adenosine MonoPhosphate (cAMP) signalling pathway. This study shows that components (microbiota, metabolites, targets and a key signalling pathway) and DPDNFs can exert combinatorial pharmacological effects against NAFLD. Overall, the integrated pharmacological approach sheds light on the relationships between GM and DPDNFs.

Keywords: cAMP signalling pathway; combinatorial pharmacological effects; dietary plant-derived natural flavonoids; gut microbiota; network pharmacology; non-alcoholic fatty liver disease.

MeSH terms

  • Flavonoids / pharmacology
  • Gastrointestinal Microbiome*
  • Humans
  • Molecular Docking Simulation
  • Network Pharmacology
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Non-alcoholic Fatty Liver Disease* / metabolism


  • Flavonoids