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Resveratrol: Evidence for Its Nephroprotective Effect in Diabetic Nephropathy.

ABSTRACT: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Dietary habits play a major role in determining the onset and progression of DM-related disorders and a proper diet (rich in fruits and vegetables) can delay or prevent the process of DM pathogenesis. Thus, increasing attention has been paid to polyphenols and polyphenol-rich foods since their increased intake has been associated with a reduced incidence of DM and its associated complications. Resveratrol is a polyphenolic phytoalexin that is mainly found in grapevines and berries. It is available in various pharmaceutical dosages and is widely recommended as a dietary supplement due to its beneficial effects. Remarkably, resveratrol's capability to effectively lower blood glucose levels without any side effects has been amply demonstrated in many in vitro and in vivo studies. Herein, we comprehensively review and discuss the nephroprotective effect of resveratrol during DN and its associated mechanisms. Resveratrol exerts its nephroprotective effects via various mechanisms including reducing oxidative stress and advanced glycation end-product (AGE) production, stimulating autophagy, inhibiting endoplasmic reticulum (ER) stress and inflammation, ameliorating lipotoxicity, activating the AMP kinase (AMPK) pathway, and modulating angiogenesis. Moreover, the use of resveratrol as an adjuvant to conventional antidiabetic therapies could be an effective approach to manage DN in humans. However, evidence is scarce to support whether resveratrol has beneficial effects in humans during DN. Therefore, clinical studies are warranted to elucidate resveratrol's role against DN.

SUBMITTER: Gowd V

PROVIDER: S-EPMC7666903 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Validation of predicted gene expression of human mesangial cells after 24h Tacrolimus stimulus Objective: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. Materials and Methods: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology. We searched for features in interference between the DN molecular model and the tacrolimus MoA molecular model already holding annotation evidence as diagnostic or prognostic biomarker in the context of DN. Results: Thirty nine molecular features were shared between the DN molecular model, holding 252 molecular features and the tacrolimus MoA molecular model, holding 209 molecular features, with six additional molecular features affected by tacrolimus in mesangial cells. Significantly affected molecular pathways by both molecular model sets included cytokine-cytokine receptor interactions, adherens junctions, TGF-beta signaling, MAPK signaling, and calcium signaling. Molecular features involved in inflammation and immune response contributing to DN progression were significantly downregulated by tacrolimus (e.g. the tumor necrosis factor alpha (TNF), interleukin 4, or interleukin 10). On the other hand, pro-fibrotic stimuli being detrimental to renal function were induced by tacrolimus like the transforming growth factor beta 1 (TGFB1), endothelin 1 (EDN1), or type IV collagen alpha 1 (COL4A1). Conclusion: Patients with DN and elevated TNF levels might benefit from tacrolimus treatment regarding maintaining GFR and reducing inflammation. TGFB1 and EDN1 are proposed as monitoring markers to assess degree of renal damage. Next to this stratification approach, the use of drug combinations consisting of tacrolimus in addition to ACE inhibitors, angiotensin receptor blockers, TGFB1- or EDN1-receptor antagonists might warrant further studies. comparison of gene expression of human mesangial cells after 24h Tacrolimus vs. Ctrl; 4 independent experiments were conducted (4xTacrolimus 24h and 4x ctrl. 24h with Drug solvent (DMSO))

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Resveratrol: Evidence for Its Nephroprotective Effect in Diabetic Nephropathy.

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