<p>Renoprotective Effect of Formononetin by Suppressing Smad3 Expression in Db/Db Mice</p>

Abstract

Purpose: Glomerular sclerosis and renal interstitial fibrosis are the most important pathologies in the development of kidney damage under diabetic conditions. Smad3 plays antagonistic roles in high glucose-induced renal tubular fibrosis, which is an important treatment target for diabetic nephropathy (DN). Formononetin (FMN) has multiple effects on diabetic vascular complications including DN. However, whether it plays an anti-fibrosis role by regulating smad3 is unclear. The purpose of this study was to evaluate the renoprotective effect of FMN by suppressing smad3 expression in db/db mice. Methods: FMN was orally administered to db/db mice with a dose of 25 or 50 mg/kg/day for 8 weeks. At the end of the study, serum, urine, and kidney samples were collected for biochemical and pathological examinations. The expressions of proteins and mRNA associated with renal fibrosis were determined by biochemical, histological, immunofluorescence, and real-time PCR analysis. Results: The results showed that FMN substantially improved the glucolipid metabolism, reduced the oxidative stress, and protected renal function in db/db mice. Meanwhile, protein and mRNA expression of smad3 and related regulatory factor of extracellular matrix deposition were significantly suppressed. Conclusion: The present study suggested that FMN has a good renoprotective effect in DN, which plays an anti-fibrosis role in db/db mice by suppressing the expression of smad3.

Formononetin Attenuates Renal Tubular Injury and Mitochondrial Damage in Diabetic Nephropathy Partly via Regulating Sirt1/PGC-1α Pathway

“…Firstly, we investigated the effects of FMN on renal function and morphological changes in diabetic rats. Several studies explored the renal protective effects of FMN in type 2 diabetes models ( Oza and Kulkarni, 2019 ; Lv et al, 2020 ; Zhuang et al, 2020 ). Our study aimed to investigate the protective effects of FMN on renal tubular impairment and mitochondrial dysfunction in STZ-induced type 1 diabetic rats.…”

Based on Network Pharmacology and Molecular Docking to Explore the Underlying Mechanism of Huangqi Gegen Decoction for Treating Diabetic Nephropathy

“…Studies have shown that formononetin can improve glucose and lipid metabolism, reduce oxidative stress, and protect the kidney in diabetic db/db mice. Moreover, the inhibition of Smad3 protein and related regulatory factors of extracellular matrix could contribute to alleviation of renal fibrosis [ 27 ]. Kaempferol has anti-inflammation, antioxidation, antidiabetes, and antiaging effects [ 28 ].…”

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“…It is compatible with [20], which showed that AST and ALT levels were reduced after A. annua L treatment. A. annua L. was reported to improve proteinuria and eliminate NS progression [21]. Many researches have also argued that ARS can minimize renal lesion in rats by inhibiting the platelet-derived plant growth factor B expression (PDGF-B) [22], metalloproteinase tissue inhibitor-2 spatiotemporal activation of protein kinase c (PKC), and its hetero-demer function [23].…”