Salidroside from Rhodiola rosea L. attenuates diabetic nephropathy in STZ induced diabetic rats via anti-oxidative stress, anti-inflammation, and inhibiting TGF-β1/Smad pathway

Introduction: Advanced glycation end products, oxidative stress, and TGF-β expression play a crucial role in pathophysiology of diabetic nephropathy. Inhibition of oxidative stress and TGF-β expression by natural traditional medicines may give an economic and safe alternative treatment option. Triphala churna, a traditional medicine, has been proved to have potent antioxidant activity, and individual components of it have shown significant antidiabetic activity. Hence, the present study was designed to study the effect of Triphala churna in diabetic nephropathy in rats. Methods: Diabetes was induced in rats by administration of streptozotocin (55 mg/kg i.p.). Four weeks after induction of diabetes, the animals were treated with Triphala churna at the doses of 250, 500, and 1,000 mg/kg for next 4 weeks. Various biochemical and urine parameters such as glucose, creatinine, blood urea nitrogen (BUN), total protein, and albumin were assessed at the end of study. Creatinine clearance, BUN clearance, and glomerular filtration rate were determined. Oxidative stress parameters such as malondialdehyde, catalase, reduced glutathione, and superoxide dismutase were determined in kidney tissues. TGF-β1 expression was measured with ELISA, immunohistochemistry, and western blot techniques. Histopathology study was carried out with haemotoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining to determine histological changes. Results: Treatment with Triphala churna significantly improved urine parameters. Triphala churna treatment also improved plasma proteins, albumin, creatinine, and BUN levels. The oxidative stress was reduced in the kidney with the treatment of Triphala churna. Histopathological studies revealed that Triphala churna reduced kidney damage. Immunohistochemistry, ELISA, and western blotting study revealed that treatment with Triphala decreased the expression of TGF-β in kidney tissues. Conclusion: From the results, it can be concluded that Triphala churna has a significant nephroprotective effect because of its capability of inhibiting oxidative stress and TGF-β in diabetes.

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Biochanin‐A has anti‐diabetic, anti‐hyperlipidemic, anti‐oxidant and protective effects on diabetic nephropathy via suppression of TGF‐β1 and PAR‐2 genes expression in kidney tissues of STZ‐induced diabetic rats

Biotechnology and Applied Biochemistry ◽

10.1002/bab.2272 ◽

2021 ◽

Author(s):

Jamal Amri ◽

Mona Alaee ◽

Rasool Babaei ◽

Zahra Salemi ◽

Reza Meshkani ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Diabetic Rats ◽

Biochanin A ◽

Protective Effects ◽

Genes Expression ◽

Anti Oxidant ◽

Tgf Β1

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Mangiferin Attenuates Diabetic Nephropathy by Inhibiting Oxidative Stress Mediated Signaling Cascade, TNFα Related and Mitochondrial Dependent Apoptotic Pathways in Streptozotocin-Induced Diabetic Rats

PLoS ONE ◽

10.1371/journal.pone.0107220 ◽

2014 ◽

Vol 9 (9) ◽

pp. e107220 ◽

Cited By ~ 94

Author(s):

Pabitra Bikash Pal ◽

Krishnendu Sinha ◽

Parames C. Sil

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Diabetic Rats ◽

Signaling Cascade ◽

Apoptotic Pathways

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Flavonoids on diabetic nephropathy: advances and therapeutic opportunities

Chinese Medicine ◽

10.1186/s13020-021-00485-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Qichao Hu ◽

Caiyan Qu ◽

Xiaolin Xiao ◽

Wenwen Zhang ◽

Yinxiao Jiang ◽

...

Keyword(s):

Oxidative Stress ◽

Natural Products ◽

Diabetic Nephropathy ◽

Metabolic Diseases ◽

Inflammatory Responses ◽

The Body ◽

Diabetic Patients ◽

Public Attention ◽

Wide Range ◽

Tgf Β1

AbstractWith the advances in biomedical technologies, natural products have attracted substantial public attention in the area of drug discovery. Flavonoids are a class of active natural products with a wide range of pharmacological effects that are used for the treatment of several diseases, in particular chronic metabolic diseases. Diabetic nephropathy is a complication of diabetes with a particularly complicated pathological mechanism that affects at least 30% of diabetic patients and represents a great burden on public health. A large number of studies have shown that flavonoids can alleviate diabetic nephropathy. This review systematically summarizes the use of common flavonoids for the treatment of diabetic nephropathy. We found that flavonoids play a therapeutic role in diabetic nephropathy mainly by regulating oxidative stress and inflammation. Nrf-2/GSH, ROS production, HO-1, TGF-β1 and AGEs/RAGE are involved in the process of oxidative stress regulation. Quercetin, apigenin, baicalin, luteolin, hesperidin, genistein, proanthocyanidin and eriodictyol were found to be capable of alleviating oxidative stress related to the aforementioned factors. Regarding inflammatory responses, IL-1, IL-6β, TNF-α, SIRT1, NF-κB, and TGF-β1/smad are thought to be essential. Quercetin, kaempferol, myricetin, rutin, genistein, proanthocyanidin and eriodictyol were confirmed to influence the above targets. As a result, flavonoids promote podocyte autophagy and inhibit the overactivity of RAAS by suppressing the upstream oxidative stress and inflammatory pathways, ultimately alleviating DN. The above results indicate that flavonoids are promising drugs for the treatment of diabetic nephropathy. However, due to deficiencies in the effect of flavonoids on metabolic processes and their lack of structural stability in the body, further research is required to address these issues.

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Lovastatin Inhibits Transforming Growth Factor-β1 Expression in Diabetic Rat Glomeruli and Cultured Rat Mesangial Cells

Journal of the American Society of Nephrology ◽

10.1681/asn.v11180 ◽

2000 ◽

Vol 11 (1) ◽

pp. 80-87

Author(s):

SUNG IL KIM ◽

DONG CHEOL HAN ◽

HI BAHL LEE

Keyword(s):

Diabetic Nephropathy ◽

Blood Glucose ◽

Transforming Growth Factor ◽

Mesangial Cells ◽

Diabetic Rats ◽

Kidney Weight ◽

Urine Albumin Excretion ◽

Urine Albumin ◽

Ecm Proteins ◽

Tgf Β1

Abstract. Diabetic nephropathy is a leading cause of end-stage renal disease and is characterized by excessive deposition of extracellular matrix (ECM) proteins in the glomeruli. Transforming growth factor-β (TGF-β) is the major mediator of excessive accumulation of ECM proteins in diabetic nephropathy through upregulation of genes encoding ECM proteins as well as downregulation of genes for ECM-degrading enzymes. It has been shown that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, delays the onset and progression of different models of experimental nephropathy. To evaluate the effect of lovastatin on the development and progression of diabetic nephropathy, streptozotocin-induced diabetic rats were studied for 12 mo. In untreated diabetic rats, there were significant increases in blood glucose, urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression in the glomeruli compared with normal control rats treated with citrate buffer only. Treatment with lovastatin in diabetic rats significantly suppressed the increase in urine albumin excretion, kidney weight, glomerular volume, and TGF-β1 mRNA expression despite high blood glucose levels. To elucidate the mechanisms of the renal effects of lovastatin, rat mesangial cells were cultured under control (5.5 mM) or high (30 mM) glucose with lovastatin alone, mevalonate alone, or with both. Under high glucose, TGF-β1 and fibronectin mRNA and proteins were upregulated. These high glucose-induced changes were suppressed by lovastatin (10 μM) and nearly completely restored by mevalonate (100 μM). These results suggest that lovastatin has a direct cellular effect independent of a cholesterol-lowering effect and delays the onset and progression of diabetic nephropathy, at least in part, through suppression of glomerular expression of TGF-β1.

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Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways

AJP Renal Physiology ◽

10.1152/ajprenal.00393.2016 ◽

2017 ◽

Vol 313 (2) ◽

pp. F414-F422 ◽

Cited By ~ 42

Author(s):

Salma Malik ◽

Kapil Suchal ◽

Sana Irfan Khan ◽

Jagriti Bhatia ◽

Kamal Kishore ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Transforming Growth Factor ◽

Mapk Pathway ◽

Histopathological Examination ◽

Fasting Blood Glucose ◽

Transforming Growth Factor Β1 ◽

Diabetic Rats ◽

Tnf Α ◽

Per Se

Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, antiapoptotic, antifibrotic, as well as antidiabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, and apigenin treatment groups (5–20 mg/kg po, respectively), apigenin per se (20 mg/kg po), and ramipril treatment group (2 mg/kg po). A single injection of STZ (55 mg/kg ip) was administered to all of the groups except control and per se groups to induce type 1 diabetes mellitus. Rats with fasting blood glucose >250 mg/dl were included in the study and randomized to different groups. Thereafter, the protocol was continued for 8 mo in all of the groups. Apigenin (20 mg/kg) treatment attenuated renal dysfunction, oxidative stress, and fibrosis (decreased transforming growth factor-β1, fibronectin, and type IV collagen) in the diabetic rats. It also significantly prevented MAPK activation, which inhibited inflammation (reduced TNF-α, IL-6, and NF-κB expression) and apoptosis (increased expression of Bcl-2 and decreased Bax and caspase-3). Furthermore, histopathological examination demonstrated reduced inflammation, collagen deposition, and glomerulosclerosis in the renal tissue. In addition, all of these changes were comparable with those produced by ramipril. Hence, apigenin ameliorated renal damage due to DN by suppressing oxidative stress and fibrosis and by inhibiting MAPK pathway.

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