Resveratrol ameliorates diabetic nephropathy in rats through negative regulation of the p38 MAPK/TGF-β1 pathway

Abstract

Resveratrol (RSV) has been shown to have a renoprotective effect against diabetic nephropathy, but the underlying mechanisms of this have not been fully elucidated. The aim of the current study was to explore the mechanisms responsible for the therapeutic effects of RSV in rat mesangial cells in vitro and in a rat model of diabetic nephropathy. The viability of CRL-2573 rat mesangial cells and their expression levels of p38, phosphorylated (p)-p38, transforming growth factor beta 1 (TGF-β1) and fibronectin were assessed in response to treatment with high glucose, with or without RSV. Diabetic nephropathy was also induced in Sprague-Dawley rats by streptozotocin treatment. At 8 weeks, basic biochemical parameters and histopathological abnormalities as well as the expression of p38, p-p38, TGF-β1 and fibronectin in rat kidneys were compared between control diabetic rats and those treated with 20 mg/kg RSV daily for 4 weeks. In the mesangial cell line, RSV inhibited high glucose-induced increases in cell viability and fibronectin expression by significantly reducing p38 mitogen-activated protein kinase (MAPK) activation and TGF-β1 expression (P<0.05). In diabetic rats, RSV significantly decreased blood glucose, serum creatinine and urinary albumin levels, as well as the kidney weight and ratio of kidney weight/body weight compared with the control group (P<0.05). Moreover, RSV ameliorated renal histological changes and downregulated the expression of p-p38, TGF-β1 and fibronectin in the kidneys of diabetic rats. These data suggested that RSV protected renal tissue from diabetes-induced injury and that this activity may be via inhibition of the p38 MAPK/TGF-β1 signaling pathway.

Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review

“…Moreover, resveratrol showed protective effects on adipose tissue in diabetic mice by preventing ROS-mediated mitochondrial fission via AMPK-dependent upregulation of Drp1 phosphorylation, and by blocking the activation of NALP3 inflammasome via inhibition of endoplasmic reticulum stress (ERS) [93]. Resveratrol also protected against diabetic complications such as myocardial fibrosis, diabetic nephropathy, and erectile dysfunction [11,88,94]. Furthermore, maternal resveratrol administration to the rats was evidenced to prevent the offspring's glucose intolerance and islet dysfunction, which were associated with gestational diabetes [91].…”

Salidroside ameliorates diabetic nephropathy in rats by activating renal AMPK/SIRT1 signaling pathway

“…In contrast, the STZ‐induced rats’ model is widely used to study the early changes in DN and characterized by severe hyperglycemia, hypoinsulinemia, and weight loss, possibly due to the increased catabolic effects of insulin deficiency, volume depletion, and osmotic diuresis (Kitada, Ogura, & Koya, ; Qiao, Gao, Wang, Wang, & Cui, ). In diabetic animal and individuals, the early clinical manifestations of the DN involve increased hyperfiltration, glomerular filtration rate (GFR), and microalbuminuria, whereas the end‐stage of the disease is characterized by severing glomerular damage, proteinuria, macroalbuminuria, oxidative stress, interstitial fibrosis, apoptosis, and impaired kidney function (Ding & Choi, ; Hayashi et al, ; Kitada et al, , ; Mima et al, ; Qiao et al, ; Reidy, Kang, Hostetter, & Susztak, ; Szrejder & Piwkowska, ; Yao, Zhang, & Chen, ).…”

“…A summary of the mechanism of action is depicted in the provided graphical abstract ( Figure 8). (Kitada, Ogura, & Koya, 2016;Qiao, Gao, Wang, Wang, & Cui, 2017). In diabetic animal and individuals, the early clinical manifestations of the DN involve increased hyperfiltration, glomerular filtration rate (GFR), and microalbuminuria, whereas the end-stage of the disease is characterized by severing glomerular damage, proteinuria, macroalbuminuria, oxidative stress, interstitial fibrosis, apoptosis, and impaired kidney function (Ding & Choi, 2014;Hayashi et al, 2001;Kitada et al, 2003Kitada et al, , 2016Mima et al, 2008;Qiao et al, 2017;Reidy, Kang, Hostetter, & Susztak, 2014;Szrejder & Piwkowska, 2019;Yao, Zhang, & Chen, 2016).…”

Resveratrol Supplementation Prevents Hypertension in Hypertensive Pregnant Rats by Increasing Sodium Excretion and Serum Nitric Oxide Level

“…Kitada et al showed that, in diabetic db/db mice, RES treatment for 8 weeks (0.3% diet) resulted in decreased urinary albumin excretion [27]. Qiao et al showed that treatment of STZ-induced diabetic SD rats with RES (20 mg/kg/day) for 4 weeks resulted in reduced serum glucose and creatinine levels [28]. Consistent with these results, we observed that the serum urea and creatinine levels, as well as the urinary protein level, were obviously increased in a rat model of pregnant hypertension.…”