Chlorogenic Acid Prevents Hyperuricemia Nephropathy via Regulating TMAO-Related Gut Microbes and Inhibiting the PI3K/AKT/mTOR Pathway

J Agric Food Chem. 2022 Aug 24;70(33):10182-10193. doi: 10.1021/acs.jafc.2c03099. Epub 2022 Aug 11.


Hyperuricemia is an independent hazard factor of renal injury and can induce renal fibrosis, promoting the development of chronic kidney disease (CKD). This study aimed to explore the probability of chlorogenic acid (CGA) as a potential substance for preventing hyperuricemia nephropathy (HN). Pretreatment with CGA downregulated SUA, BUN, and CR levels, relieved oxidative stress and inflammatory response, alleviated kidney fibrosis, and contributed to the prevention of HN. In the gut microbiota, Blautia, Enterococcus, and Faecalibaculum related to trimethylamine N-oxide (TMAO) synthesis were significantly increased in HN rats. In addition, it showed a significant increase in serum TMAO content in HN rats. However, CGA regulated the cascade response of the microbiota-TMAO signaling to reverse the increase of serum TMAO. CGA also decreased the protein expression of protein kinase B (AKT) phosphorylation, phosphatidylinositide 3-kinase (PI3K), and mammalian target of rapamycin (mTOR) by reducing the production of TMAO. CGA delayed kidney fibrosis in HN rats as evidenced by regulating the cascade response of the microbiota-TMAO-PI3K/AKT/mTOR signaling pathway. In summary, CGA can be an excellent candidate for HN prevention.

Keywords: gut microbiota; hyperuricemia nephropathy; inflammation; kidney fibrosis; trimethylamine N-oxide.

MeSH terms

  • Animals
  • Chlorogenic Acid
  • Fibrosis
  • Gastrointestinal Microbiome*
  • Hyperuricemia* / chemically induced
  • Hyperuricemia* / drug therapy
  • Hyperuricemia* / genetics
  • Mammals / metabolism
  • Methylamines / metabolism
  • Phosphatidylinositol 3-Kinase
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Rats
  • Renal Insufficiency, Chronic* / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • Uric Acid


  • Methylamines
  • Uric Acid
  • Chlorogenic Acid
  • mTOR protein, rat
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • trimethyloxamine