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.

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.

• Authors: Henry Cherng-Han Lin, Catherine Reena Paul, Chia-Hua Kuo, Yung-Hsien Chang, William Shao-Tsu Chen, Tsung-Jung Ho, Cecilia-Hsuan Day, Bharath Kumar Velmurugan, Yuhsin Tsai, Chih-Yang Huang
• Journal: Journal of food biochemistry (J Food Biochem) Vol. 46 Issue 5 Pg. e14041 (05 2022) ISSN: 1745-4514 [Electronic] United States
• PMID: 35064587 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Wiley Periodicals LLC.

Chemical References

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

Topics

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