Therapy For Diabetic Nephropathy Research Articles

In silico ADME-T and molecular docking study of phytoconstituents from Tithonia diversifolia (Hemsl.) A. Gray on various targets of diabetic nephropathy

Context: Tithonia diversifolia (Hemsl.) A. Grayhas been known for treatment of diabetes mellitus, yet its mechanism as anti-diabetic has not been defined. There are various therapeutic targets for diabetes and its complication such as diabetic nephropathy. Aims: To investigate the mechanism of phytoconstituents in Tithonia diversifolia to various targets of diabetic nephropathy and predict the pharmacokinetic profile such as absorption, distribution, metabolism, elimination, and toxicity (ADME-T). Methods: Eighteen phytoconstituents in Tithonia diversifolia were analyzed for drug-likeness. The molecular docking of molecules was performed to protein targets, then its molecular interaction was determined. ADME-T properties were predicted using three different web servers. Results: Drug-likeness analysis showed that all the phytoconstituents were within the range set by Lipinski’s rule of five. This study showed that Tithonia diversifolia have potential as a candidate for diabetic nephropathy therapy agent with various mechanisms by inhibiting α-glucosidase, ACE, ALR, DPP-4, LMW-PTP, RAGE, SGLT2, SUR1, and an analog of PPAR-γ. 5-Caffeoylquinic acid, catechin, diversifolin, hispidulin, tagitinin A, tagitinin C, tagitinin F, tithonine, and tirotundin were phytoconstituents with a high binding affinity to several proteins. β-gurjunene, tagitinin A,tagitinin C, tagitinin F, and tirotundin were predicted to have a better ADME-T properties than other compounds. In summary, tagitinin A, tagitinin C, tagitinin F, and tirotundin were showed the high binding affinity to various diabetes-related proteins and have a good ADME-T profile. Conclusions: This study suggests that Tithonia diversifolia constituents have potential properties as an anti-diabetic nephropathy agent, and further studies to analyze its potency are required.

Anti-Oxidative Therapy in Diabetic Nephropathy.

Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the disease. Diabetic nephropathy is one of the leading causes of end-stage kidney failure. Kidney damage in diabetic nephropathy is largely attributed to the increased oxidative stress, affecting its metabolic activity, metabolic pathways, and hemodynamic pathways. In diabetic patients, hyperglycemia causes an increase in the production of reactive oxygen species that further increase oxidative stress. These reactive oxygen species are created through a variety of pathways, providing the opportunity for treatment using anti-oxidative defense mechanisms to prevent vascular injury. This review will give an overview of oxidative stress, along with the current treatments and limitations of diabetic nephropathy. We will also discuss the potential of antioxidative therapies, with an emphasis on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.

Markers of oxidative damage lipids and DNA in men with type 1 diabetes mellitus and different levels of albuminuria

BACKGROUND : Diabetic nephropathy is a specific kidney damage that affects up to 40% of type 1 diabetes mellitus patients. There is still insufficient knowledge about oxidative stress at the different levels of albuminuria. AIM : To assess the indicators of oxidative damage to lipids, DNA and antioxidant defense in men with type 1 diabetes mellitus and albuminuria different levels. MATERIALS AND METHODS: The study was conducted during 2018–2019. The main group included 56 men of reproductive age with type 1 diabetes mellitus (T1DM) divided into 2 groups: 24 patients with albuminuria level A1 (group A1) and 32 patients with albuminuria level A2 (group A2). The control group consisted of 28 healthy men. The oxidative stress indicators content, as well as the activity of antioxidant defense system various links was evaluated. Spectrophotometric, fluorimetric and enzyme immunoassay methods were used. RESULTS : In patients of the A1 group there were higher values of the median of primary — conjugated dienes, secondary — ketodienes and conjugated trienes, final — Schiff bases products and 8-hydroxy-2 ’ -deoxyguanosine in comparison with the control. Similar changes in patients of the A2 group were found. Intergroup differences related to increased median values of TBARs and 8-hydroxy-2 ’ -deoxyguanosine in patients of the A2 group compared with A1 group. The activity of the antioxidant defense system in A1 group relative to the control by increased values of the glutathione peroxidase, reduced glutathione, oxidized glutathione median, and retinol was characterized. A2 group had higher values of glutathione peroxidase, reduced glutathione and oxidized glutathione medians in comparison with controls. Correlation analysis in A1 group showed the relationships between the duration of the disease and the products of lipid peroxidation, glycated hemoglobin with 8-hydroxy-2 ’ -deoxyguanosine. In A2 group, there was a relationship between the albumin/creatinine ratio and the duration of the disease, glomerular filtration rate and creatinine level. CONCLUSION : In men with T1DM, regardless of the albuminuria level, there are higher values of the oxidative damage lipids and DNA parameters, as well as the presence of close relationships between these parameters and the duration of the disease, which can be used to develop potential strategies for the prevention and early therapy of diabetic nephropathy.

Possible Synergistic Effect of Curcumin on Captopril /Losartan Combined Therapy in Diabetic Nephropathy

Possible Synergistic Effect of Curcumin on Captopril /Losartan Combined Therapy in Diabetic Nephropathy

Stimulation of Angiotensin Converting Enzyme 2: A Novel Treatment Strategy for Diabetic Nephropathy.

Despite current therapies for diabetic nephropathy, many patients continue to progress to end-stage renal disease requiring renal replacement therapy. While the precise mechanisms underlying diabetic nephropathy remain to be determined, it is well established that chronic activation of the renin angiotensin aldosterone system (RAAS) plays a substantial role in the pathogenesis of diabetic nephropathy. Angiotensin converting enzyme 2 (ACE2), the enzyme responsible for activating the reno-protective arm of the RAAS converts angiotensin (Ang) II into Ang 1-7 which exerts reno-protective effects. Chronic RAAS activation leads to kidney inflammation and fibrosis, and ultimately lead to end-stage kidney disease. Currently, angiotensin converting enzyme inhibitors and Ang II receptor blockers are approved for renal fibrosis and inflammation. Targeting the reno-protective arm of the RAAS should therefore, provide further treatment options for kidney fibrosis and inflammation. In this review, we examine how targeting the reno-protective arm of the RAAS can ameliorate kidney inflammation and fibrosis and rescue kidney function in diabetic nephropathy. We argue tissue ACE2 stimulation provides a unique and promising therapeutic approach for diabetic nephropathy.

LncRNA KCNQ1OT1 regulated high glucose-induced proliferation, oxidative stress, extracellular matrix accumulation, and inflammation by miR-147a/SOX6 in diabetic nephropathy (DN).

Long non-coding RNAs (lncRNAs) have been proved to play critical roles in diabetic nephropathy (DN). This study aimed to investigate the functions and underlying mechanism of potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) in DN. Blood samples were obtained from 33 DN patients and 30 healthy volunteers. Kidney biopsies tissues of DN patients (n = 10) and patients with normal kidney morphology (n = 10) were collected. We found that KCNQ1OT1 was markedly overexpressed in the blood and kidney biopsies tissues of DN patients, as well as in high glucose (HG)-cultured human glomerular mesangial (HGMC) cells. Knockdown of KCNQ1OT1 suppressed proliferation, extracellular matrix (ECM) accumulation, inflammation, and oxidative stress in HG-treated HGMC cells in vitro. KCNQ1OT1 functioned as a sponge for microRNA-147a (miR-147a), and SRY-Box Transcription Factor 6 (SOX6) was directly targeted by miR-147a. Downregulation of miR-147a or upregulation of SOX6 partly overturned the prohibitive effects of KCNQ1OT1 knockdown or miR-147a overexpression on proliferation, ECM accumulation, inflammation, and oxidative stress in HG-treated HGMC cells. Altogether, KCNQ1OT1 mediated the proliferation, ECM accumulation, inflammation, and oxidative stress in HG-treated HGMC cells via miR-147a/SOX6 axis, which might be a novel target for DN therapy.

Regression of diabetic nephropathy by treatment with empagliflozin in BTBR ob/ob mice.

The sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin lowers blood glucose via reduced tubular reabsorption of filtered glucose and is an important new therapy for diabetic nephropathy (DN). This study tested whether treatment with empagliflozin would ameliorate proteinuria and the pathologic alterations of DN including podocyte number and integrity in the leptin-deficient BTBR ob/ob mouse model of DN. Study cohorts included wild-type (WT) BTBR mice, untreated diabetic BTBR ob/ob mice and mice treated with empagliflozin for 6 weeks after development of established DN at 18 weeks of age. Hyperglycemia, proteinuria, serum creatinine, accumulation of mesangial matrix and the extent of mesangiolysis were reversed with empagliflozin treatment. Treatment with empagliflozin resulted in an increased podocyte number and podocyte density, improvement in the degree of podocyte foot process effacement and parietal epithelial cell activation. SGLT2 inhibition reduced renal oxidative stress, measured by urinary excretion of markers of RNA/DNA damage and in situ demonstration of decreased carbonyl oxidation. There was no discernable difference in accumulations of advanced glycation end-products by immunohistochemistry. The structural improvements seen in BTBR ob/ob mice treated with empagliflozin provide insights into potential long-term benefits for humans with DN, for whom there is no comparable biopsy information to identify structural changes effected by SGLT2 inhibition. The findings suggest SGLT2 inhibition may ameliorate DN through glucose lowering-dependent and -independent mechanisms that lead to podocyte restoration and delay or reversal of disease progress.

Demethylbellidifolin, a potential aldose reductase inhibitor ameliorates diabetic nephropathy by regulating the polyol pathway

BackgroundLots of plants in genus Swertia are widely used in the traditional medicine as the treatment for T2DM and its complications in Asia. However, the pharmacodynamic material basis and underlying mechanisms of these plants are still incompletely studied. Inhibition of aldose reductase to regulate polyol pathway is considered to be one effective strategy to treat many complications arising from diabetes. AimThe inhibitory effect against aldose reductase of typical components from the genus Swertia were examined, and further verified in db/db mice model to explore its in vivo renal protective ability and underlying mechanism. MethodsHuman recombinant aldose reductase (AR) was applied to detect the inhibitory activity of these components from genus Swetia in vitro, and the most active one was further analyzed in molecular docking experiment. Then, db/db diabetic mice model were employed to investigate the renal protective effects in vivo. Oxidative stress and renal function related indicators were determined using biochemical kit. Histopathological examination of kidney was conducted to evaluate pathological variations. RT-PCR was applied to measure the level of AR mRNA in renal cortex. Expression of AR, TGF-β1, Collagen Ⅳ, Nephrin and Podocin in kidney tissues were assessed by Western blot. ResultsIt turned out that demethylbellidifolin (DMB) showed the strongest inhibitory activity against AR, with an IC50 of 1.29 ± 0.16 μM, by stabilizing the active site of AR. In vivo experiment confirmed that DMB could remarkably reduce blood glucose and albuminuria level, and alleviate oxidative stress response. Meanwhile, histopathological examination also displayed that the kidney damage in db/db mice was significantly improved after treatment with DMB. Further mechanism study indicated that DMB could prevent the accumulation of sorbitol, one of the polyol pathway products. Besides, DMB could also maintaining the integrity of podocytes structure by up-regulating the expression of Nephrin and Podocin, and exert renal protective effects by inhibiting the expression of AR, Collagen Ⅳ and TGF-β1 in the polyol pathway. ConclusionsThese findings indicated that genus Swertia could be an important plant sources of aldose reductase inhibitors, and one of its typical components, DMB, exerted a therapeutic role in the treatment of diabetic nephropathy by regulating the polyol pathway to relieve the injury of cells in the kidney, and may represent a promising renal protective medication for diabetic nephropathy therapy.

Are the Protean Effects of Pentoxifylline in the Therapy of Diabetes and Its Complications Still Relevant?

Pentoxifylline (Px) has protean effects that can be utilized in the therapy of diabetes and its complications. There have been well-documented but often inconclusive improvements in peripheral arterial disease, foot ulcers, peripheral neuropathy, nephropathy, retinopathy, ischemic heart disease and cerebrovascular disease. In addition, non-alcoholic steatosis and steatohepatitis, which are closely associated with insulin resistance and type 2 diabetes, have been shown to improve with pentoxifylline. Surprisingly, pentoxifylline modestly improves insulin resistance through improvements in capillary blood flow as well as beta cell function and decreased hepatic glucose production. The therapeutic effects of pentoxifylline are complementary to the effects of drugs such as blockers of the renin-angiotensin-aldosterone system when utilized in the therapy of diabetic nephropathy.

Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity.

The rhizome of Ligusticum chuanxiong Hort. has been widely used for the therapy of diabetic nephropathy (DN) in traditional Chinese medicine (TCM). The nuclear transcription factor erythroid 2-related factor (Nrf2) is a potential target for treating DN. The purpose of this research was to study the chemical constituents from the rhizome of L. chuanxiong, evaluate their Nrf2 inducing activity, and find the molecules with potential therapeutic effect against DN. In this study, two new phthalides (1-2) along with twenty-seven known constituents were obtained from the rhizome of L. chuanxiong. Their structures were elucidated through various spectroscopic methods. Twelve constituents, including eight phthalides (2, 5, 6,10-13, 14) and four other compounds (17, 18, 20,28), stimulated NAD(P)H: quinone reductase (QR) activity, suggesting that these bioactive constituents were potential Nrf2 activators. Among the isolated compounds, phthalide levistolide A (LA, 14) upregulated the protein levels of Nrf2, NQO1, and γ-GCS in a dose-dependent manner. Our results implied that the clinical application of the rhizome of L. chuanxiong as an anti-DN drug in TCM might be attributed to the Nrf2 inducing effect of phthalides. Thus, phthalides is a group of promising leading molecules for discovering anti-DN agents.

LncRNA SOX2OT alleviates mesangial cell proliferation and fibrosis in diabetic nephropathy via Akt/mTOR-mediated autophagy

BackgroundAccumulating evidences have demonstrated that long non-coding RNAs (lncRNAs) are involved in the pathophysiology of diabetic nephropathy (DN). lncRNA SOX2OT plays an essential role in many diseases, including diabetes. Herein, we aim to investigate the underlying mechanism of lncRNA SOX2OT in DN pathogenesis.MethodsStreptozotocin-induced DN mouse models and high glucose-induced mouse mesangial cells were constructed to examine the expression pattern of lncRNA SOX2OT. The activation of autophagy was evaluated using immunohistochemistry, immunofluorescence and western blot analysis, respectively. SOX2OT overexpressing plasmid was applied to further verify the functional role of SOX2OT in DN pathogenesis. CCK-8 and EDU assays were performed to the proliferation of mesangial cells. Additionally, rapamycin, the inhibitor of mTOR signaling, was used to further clarify whether SOX2OT controls DN development through Akt/mTOR pathway.ResultslncRNA SOX2OT was markedly down-regulated both in streptozotocin-induced DN mice and high glucose-induced mouse mesangial cells. Moreover, overexpression of lncRNA SOX2OT was able to diminish the suppression of autophagy and alleviate DN-induced renal injury. Functionally, CCK-8 and EDU assays indicated that lncRNA SOX2OT overexpression significantly suppressed the proliferation and fibrosis of mesangial cells. Additionally, an obvious inhibition of Akt/mTOR was also observed with lncRNA SOX2OT overexpression, which was then further verified in vivo.ConclusionIn summary, we demonstrated that lncRNA SOX2OT alleviates the pathogenesis of DN via regulating Akt/mTOR-mediated autophagy, which may provide a novel target for DN therapy.

High glucose-stimulated enhancer of zeste homolog-2 (EZH2) forces suppression of deptor to cause glomerular mesangial cell pathology

Function of mTORC1 and mTORC2 has emerged as a driver of mesangial cell pathologies in diabetic nephropathy. The mechanism of mTOR activation is poorly understood in this disease. Deptor is a constitutive subunit and a negative regulator of both mTOR complexes. Mechanistic investigation in mesangial cells revealed that high glucose decreased the expression of deptor concomitant with increased mTORC1 and mTORC2 activities, induction of hypertrophy and, expression of fibronectin and PAI-1. shRNAs against deptor mimicked these pathologic outcomes of high glucose. Conversely, overexpression of deptor significantly inhibited all effects of high glucose. To determine the mechanism of deptor suppression, we found that high glucose significantly increased the expression of EZH2, resulting in lysine-27 tri-methylation of histone H3 (H3K27Me3). Employing approaches including pharmacological inhibition, shRNA-mediated downregulation and overexpression of EZH2, we found that EZH2 regulates high glucose-induced deptor suppression along with activation of mTOR, mesangial cell hypertrophy and fibronectin/PAI-1 expression. Moreover, expression of hyperactive mTORC1 reversed shEZH2-mediated inhibition of hypertrophy and expression of fibronectin and PAI-1 by high glucose. Finally, in renal cortex of diabetic mice, we found that enhanced expression of EZH2 is associated with decreased deptor levels and increased mTOR activity and, expression of fibronectin and PAI-1. Together, our findings provide a novel mechanism for mTOR activation via EZH2 to induce mesangial cell hypertrophy and matrix expansion during early progression of diabetic nephropathy. These results suggest a strategy for leveraging the intrinsic effect of deptor to suppress mTOR activity via reducing EZH2 as a novel therapy for diabetic nephropathy.

Effect of neutrophil-like melanin biomimic photothermal nanoparticles on glomerular mesangial cells in rats with gestational diabetic nephropathy

Gestational diabetes mellitus (GDM) is a disease with abnormal blood glucose for the first time in gestation, and its main harm is vascular lesions, usually diabetic kidney damage. A new glucose ligand modified neutrophil-like cell membrane coated melanin nanoparticle (Melanin@Glc-NCM) was designed and prepared. Through the results of cell and animal experiments the research confirmed that under near-infrared irradiation, Melanin@Glc-NCM achieved excellent kidney-targeted drug delivery. In addition, the results of photothermal therapy in diabetic nephropathy of gestational rats demonstrated that Melanin@Glc-NCM could promote glomerular mesangial cell (GMC) apoptosis and restrain GMC hyperproliferation after near-infrared irradiation to protect the kidney as a therapeutic drug for diabetic nephropathy of gestational rats.

The Multi-Therapeutic Role of MSCs in Diabetic Nephropathy.

Diabetic nephropathy (DN) is one of the most common diabetes mellitus (DM) microvascular complications, which always ends with end-stage renal disease (ESRD). Up to now, as the treatment of DN in clinic is still complicated, ESRD has become the main cause of death in diabetic patients. Mesenchymal stem cells (MSCs), with multi-differentiation potential and paracrine function, have attracted considerable attention in cell therapy recently. Increasing studies concerning the mechanisms and therapeutic effect of MSCs in DN emerged. This review summarizes several mechanisms of MSCs, especially MSCs derived exosomes in DN therapy, including hyperglycemia regulation, anti-inflammatory, anti-fibrosis, pro-angiogenesis, and renal function protection. We also emphasize the limitation of MSCs application in the clinic and the enhanced therapeutic role of pre-treated MSCs in the DN therapy. This review provides balanced and impartial views for MSC therapy as a promising strategy in diabetic kidney disease amelioration.

Lagerstroemia speciosa extract ameliorates oxidative stress in rats with diabetic nephropathy by inhibiting AGEs formation

Diabetes mellitus is amongst the most severe incurable diseases affecting a huge number of people everywhere in the world. Diabetic nephropathy (DN) is the main cause for kidney disease, possibly due to the lack of appropriate DN treatments. The current study is to assess the role of Lagerstroemia speciosa extract (LSE) in the mitigation of DN in a streptozotocin rat model of hyperlipidemia and hyperglycemia. The animal model of DN was induced in Sprague Dawley rats by administering streptozotocin and fed on a western diet for six weeks. The administration of LSE treatment at a dose of 400 mg/kg for six weeks. LSE showed a significant decline in enhanced biochemical parameters, for instance, glucose level, creatinine, and lipid profile. LSE treatment lowered the enhanced albumin level. The advanced glycation end-product level in kidneys was significantly reduced along with augmentation in the glutathione level and a decrease in lipid peroxidation. The inflammatory markers were also reduced considerably. Thus, LSE treatment effectively protects against streptozotocin-induced nephrotoxicity in rats. LSE might act as a possible adjuvant for DN therapy and needs to be investigated further.

Network Pharmacology Analysis of ZiShenWan for Diabetic Nephropathy and Experimental Verification of Its Anti-Inflammatory Mechanism.

BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The inflammatory response plays a critical role in DN. ZiShenWan (ZSW) is a classical Chinese medicinal formula with remarkable clinical therapeutic effects on DN, but its pharmacological action mechanisms remain unclear.AimIn this study, a network pharmacology approach was applied to investigate the pharmacological mechanisms of ZSW in DN therapy. Based on the results of network analysis, the core targets and signaling pathways related to anti-inflammatory effect were verified via experiments in vivo.MethodsThe candidate chemical ingredients of ZSW as well as its putative targets and known therapeutic targets of DN were acquired from appropriate databases. The “herb-ingredient-target” network for ZSW in DN treatment was established. The protein–protein interaction (PPI) network of potential targets was constructed to screen the core targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition to biochemical and pathological indicators, the core targets and signaling pathways associated with inflammation were partially validated in db/db mice at molecular level.ResultsA total of 56 active ingredients in ZSW and 166 DN-related targets were selected from databases. A high proportion of core targets and top signaling pathways participate in inflammation. ZSW markedly alleviated renal injuries pathologically and regulated related biomarkers. In particular, ZSW significantly inhibited the exaggerated release of inflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor receptor (TNF)-ɑ, and monocyte chemotactic protein (MCP)-1 as well as regulating p38 mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinase (PI3K)–protein kinase B (Akt) signaling pathways in db/db mice.ConclusionThis study first comprehensively investigated the active ingredients, potential targets, and molecular mechanism of ZSW as a therapy for DN. ZSW achieved renoprotective effects in DN via regulation of multiple targets and signaling pathways, especially by alleviating inflammation. Results indicate that ZSW is a promising multi-target therapeutic approach for DN treatment.

Clinical Nutrition Therapy of Diabetic Nephropathy

Clinical Nutrition Therapy of Diabetic Nephropathy

Mesenchymal Stem Cells: An Overview of Their Potential in Cell-Based Therapy for Diabetic Nephropathy.

Diabetic nephropathy (DN) is a devastating complication associated with diabetes mellitus, and it is the leading cause of end-stage renal diseases (ESRD). Over the last few decades, numerous studies have reported the beneficial effects of stem cell administration, specifically mesenchymal stem or stromal cells (MSCs), on tissue repair and regeneration. MSC therapy has been considered a promising strategy for ameliorating the progression of DN largely based on results obtained from several preclinical studies and recent Phase I/II clinical trials. This paper will review the recent literature on MSC treatment in DN. In addition, the roles and potential mechanisms involved in MSC treatment of DN will be summarized, which may present much needed new drug targets for this disease. Moreover, the potential benefits and related risks associated with the therapeutic action of MSCs are elucidated and may help in achieving a better understanding of MSCs.

Nephroprotective role of nanoencapsulated Tinospora cordifolia (Willd.) using polylactic acid nanoparticles in streptozotocin-induced diabetic nephropathy rats.

Currently, the field of nanomedicine, which uses active compounds from medicinal plants, has emerged as a therapy for diabetic nephropathy. From this study, the renoprotective effect of TC‐loaded PLA Nanoparticles (TC‐PLA NPs) on streptozotocin (STZ)‐induced diabetic nephropathy rats was investigated. The results showed that the nephroprotective effect of TC‐PLA NPs reduces the blood glucose level, regulates the renal parameters, decreases the cytokine levels and reduces the mRNA expressions level of different genes related to diabetic nephropathy.

An updated pharmacological insight of resveratrol in the treatment of diabetic nephropathy.

As one of the most common complications of diabetes, nephropathy develops in approximately 40% of diabetic individuals. Although end stage kidney disease is known as one of the most consequences of diabetic nephropathy, the majority of diabetic individuals might die from cardiovascular diseases and infections before renal replacement treatment. Moreover, the routine medical treatments for diabetes hold undesirable side effects. The explosive prevalence of diabetes urges clinicians and scientists to investigate the complementary or alternative therapies. Phytochemicals are emerging as alternatives with a wide range of therapeutic effects on various pathologies, including diabetic kidney disease. Of those phytochemicals, resveratrol, a natural polyphenolic stilbene, has been found to exert a broad spectrum of health benefits via various signaling molecules. In particular, resveratrol has gained a great deal of attention because of its anti-oxidative, anti-inflammatory, anti-diabetic, anti-obesity, cardiovascular-protective, and anti-tumor properties. In the renal system, emerging evidence shows that resveratrol has already been used to ameliorate chronic or acute kidney injury. This review critically summarizes the current findings and molecular mechanisms of resveratrol in diabetic renal damage. In addition, we will discuss the adverse and inconsistent effects of resveratrol in diabetic nephropathy. Although there is increasing evidence that resveratrol affords great potential in diabetic nephropathy therapy, these results should be treated with caution before its clinical translation. In addition, the unfavorable pharmacokinetics and/or pharmacodynamics profiles, such as poor bioavailability, may limit its extensive clinical applications. It is clear that further research is needed to unravel these limitations and improve its efficacy against diabetic nephropathy. Increasing investigation of resveratrol in diabetic kidney disease will not only help us better understand its pharmacological actions, but also provide novel potential targets for therapeutic intervention.