Glycyrrhiza uralensis root extract ameliorates high glucose-induced renal proximal tubular fibrosis by attenuating tubular epithelial-myofibroblast transdifferentiation by targeting TGF-β1/Smad/Stat3 pathway

J Food Biochem. 2022 May;46(5):e14041. doi: 10.1111/jfbc.14041. Epub 2022 Jan 21.

Abstract

Growing evidences indicate that high glucose toxicity-associated fibrotic effects play a pivotal role in diabetic nephropathy (DN). Tubular epithelial-myofibroblast transdifferentiation is a major hallmark of renal fibrosis event under diabetic stress. Roots of Glycyrrhiza uralensis (Radix glycyrrhizae) used as a sweetener and traditional Chinese medicine possess high potential for renal protection. In this study, a cell model for high glucose (HG) injury with HK-2 renal proximal tubular epithelial cell line and a type-II-diabetes model with Apoeem1/Narl /Narl mice was established and the beneficial effects of aqueous R. glycyrrhizae extract (RGE) was investigated. RGE-induced regulation on the high glucose-induced excessive production of TGF-β1 and the Smad/Stat3 mechanisms of renal fibrosis were determined. HK-2 cells were challenged with 45 mM of high glucose for 48 hr. Following high glucose challenge, the cells were treated with 0.5, 1, and 1.5 mg/ml concentrations of RGE. The effect of RGE on DN was determined using high fructose diet-induced type-II-diabetes in Apoeem1/Narl /Narl mice models. Our results showed that RGE suppressed the expression of HG-induced TGFβ signaling and associated fibrosis mechanism better than the pharmacological drug acarbose. These data suggest that RGE as a potential herbal supplement in attenuating fibrosis-associated diabetic nephropathy and a potential agent in diabetes treatments.

Keywords: Glycyrrhizae Radix; diabetic nephropathy; fibrosis; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Transdifferentiation
  • Diabetic Nephropathies* / drug therapy
  • Diabetic Nephropathies* / metabolism
  • Drugs, Chinese Herbal* / pharmacology
  • Fibrosis
  • Glucose
  • Glycyrrhiza uralensis* / chemistry
  • Humans
  • Mice
  • Myofibroblasts / metabolism
  • Plant Extracts / pharmacology
  • Signal Transduction
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Drugs, Chinese Herbal
  • Plant Extracts
  • Transforming Growth Factor beta1
  • Glucose