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

• Published in: Journal of food biochemistry 2022-05, Vol.46 (5), p.e14041-n/a
• Main Authors: Lin, Henry Cherng‐Han, Paul, Catherine Reena, Kuo, Chia‐Hua, Chang, Yung‐Hsien, Chen, William Shao‐Tsu, Ho, Tsung‐Jung, Day, Cecilia‐Hsuan, Velmurugan, Bharath Kumar, Tsai, Yuhsin, Huang, Chih‐Yang
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins E - pharmacology; Apolipoproteins E - therapeutic use; Cell Transdifferentiation; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - metabolism; diabetic nephropathy; Drugs, Chinese Herbal - pharmacology; Fibrosis; Glucose; Glycyrrhiza uralensis - metabolism; Glycyrrhizae Radix; inflammation; Mice; Myofibroblasts - metabolism; Signal Transduction; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism
• ISSN: 0145-8884; 1745-4514
• DOI: 10.1111/jfbc.14041

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. TGF‐β is the major mediator of tubular epithelial–myofibroblast transdifferentiation that plays a pathogenic role in renal tubulointerstitial fibrosis particularly in conditions like diabetic nephropathy. TGF‐β‐mediated fibrosis under hyperglycemic condition is effectively attenuated by RGE treatment and by suppressing the Smad and Stat pathway of renal fibrosis.