Astragalus membranaceus and Panax notoginseng, the Novel Renoprotective Compound, Synergistically Protect against Podocyte Injury in Streptozotocin-Induced Diabetic Rats

This study was aimed at investigating the synergistical protective effects of Astragalus membranaceus (AG) and Panax notoginseng (NG) on podocyte injury in diabetic rats. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at 55 mg/kg. Diabetic rats were then orally administrated with losartan, AG, NG, and AG plus NG (2 : 1) for 12 weeks. Albuminuria, biochemical markers, renal histopathology, and podocyte number per glomerulus were measured. Podocyte apoptosis was determined by triple immunofluorescence labeling including TUNEL assay, WT1, and DAPI. Renal expression of nephrin, α-dystroglycan, Bax, Bcl-xl, and Nox4 was evaluated by immunohistochemistry, western blot, and RT-PCR. AG plus NG ameliorated albuminuria, renal histopathology, and podocyte foot process effacement to a greater degree than did AG or NG alone. The number of podocytes per glomerulus, as well as renal expression of nephrin, α-dystroglycan, and Bcl-xl, was decreased, while podocyte apoptosis, as well as renal expression of Bax and Nox4, was increased in diabetic rats. All of these abnormalities were partially restored by AG plus NG to a greater degree than did AG or NG alone. In conclusion, AG and NG synergistically ameliorated diabetic podocyte injury partly through upregulation of nephrin, α-dystroglycan, and Bcl-xl, as well as downregulation of Bax and Nox4. These findings might provide a novel treatment combination for DN.

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Astragaloside II Ameliorated Podocyte Injury and Mitochondrial Dysfunction in Streptozotocin-Induced Diabetic Rats

Frontiers in Pharmacology ◽

10.3389/fphar.2021.638422 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jun Su ◽

Chongting Gao ◽

Ling Xie ◽

Ying Fan ◽

Yilan Shen ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Tissue Injury ◽

Morphological Changes ◽

Mitochondrial Dynamics ◽

Diabetic Rats ◽

Control Group ◽

Protective Effects ◽

Podocyte Injury ◽

Renal Histopathology ◽

Related Proteins

Astragaloside II (AS II), a novel saponin purified from Astragalus membranes, has been reported to modulate the immune response, repair tissue injury, and prevent inflammatory response. However, the protective effects of AS II on podocyte injury in diabetic nephropathy (DN) have not been investigated yet. In this study, we aimed to investigate the beneficial effects of AS II on podocyte injury and mitochondrial dysfunction in DN. Diabetes was induced with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg in rats. Diabetic rats were randomly divided into four groups, namely, diabetic rats and diabetic rats treated with losartan (10 mg·kg−1·d−1) or AS II (3.2 and 6.4 mg·kg−1·d−1) for 9 weeks. Normal Sprague-Dawley rats were chosen as nondiabetic control group. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology and podocyte apoptosis, and morphological changes were evaluated. Expressions of mitochondrial dynamics-related and autophagy-related proteins, such as Mfn2, Fis1, P62, and LC3, as well as Nrf2, Keap1, PINK1, and Parkin, were examined by immunohistochemistry, western blot, and real-time PCR, respectively. Our results indicated that AS II ameliorated albuminuria, renal histopathology, and podocyte foot process effacement and podocyte apoptosis in diabetic rats. AS II also partially restored the renal expression of mitochondrial dynamics-related and autophagy-related proteins, including Mfn2, Fis1, P62, and LC3. AS II also increased the expression of PINK1 and Parkin associated with mitophagy in diabetic rats. Moreover, AS II facilitated antioxidative stress ability via increasing Nrf2 expression and decreasing Keap1 protein level. These results suggested that AS II ameliorated podocyte injury and mitochondrial dysfunction in diabetic rats partly through regulation of Nrf2 and PINK1 pathway. These important findings might provide an innovative therapeutic strategy for the treatment of DN.

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The novel role of TRPC6 in vitamin D ameliorating podocyte injury in STZ-induced diabetic rats

Molecular and Cellular Biochemistry ◽

10.1007/s11010-014-2242-9 ◽

2014 ◽

Vol 399 (1-2) ◽

pp. 155-165 ◽

Cited By ~ 26

Author(s):

Xiaoliang Zhang ◽

Zhixia Song ◽

Yinfeng Guo ◽

Min Zhou

Keyword(s):

Vitamin D ◽

Diabetic Rats ◽

The Novel ◽

Podocyte Injury

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Xuesaitong Protects Podocytes from Apoptosis in Diabetic Rats through Modulating PTEN-PDK1-Akt-mTOR Pathway

Journal of Diabetes Research ◽

10.1155/2020/9309768 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Rui Xue ◽

Ruonan Zhai ◽

Ling Xie ◽

Zening Zheng ◽

Guihua Jian ◽

...

Keyword(s):

Diabetic Kidney Disease ◽

Morphological Changes ◽

Panax Notoginseng ◽

Diabetic Rats ◽

Mtor Pathway ◽

Phosphorylated Akt ◽

Immunofluorescence Labelling ◽

Stage Renal Disease ◽

End Stage ◽

Renal Expression

Diabetic kidney disease (DKD) is a major cause of end-stage renal disease (ESRD), and therapeutic strategies for delaying its progression are limited. Loss of podocytes by apoptosis characterizes the early stages of DKD. To identify novel therapeutic options, we investigated the effects of Xuesaitong (XST), consisting of total saponins from Panax notoginseng, on podocyte apoptosis in streptozotocin- (STZ-) induced diabetic rats. XST (5 mg/kg·d) or Losartan (10 mg/kg·d) was given to diabetic rats for 12 weeks. Albuminuria, renal function markers, and renal histopathology morphological changes were examined. Podocyte apoptosis was determined by triple immunofluorescence labelling including a TUNEL assay, WT1, and DAPI. Renal expression of Nox4, miRNA-214, PTEN, PDK1, phosphorylated Akt, mTOR, and mTORC1 was detected. In diabetic rats, severe hyperglycaemia and albuminuria developed, and apoptotic podocytes were markedly increased in diabetic kidneys. However, XST attenuated albuminuria, mesangial expansion, podocyte apoptosis, and morphological changes of podocytes in diabetic rats. Decreased expression of PTEN, as well as increased expression of Nox4, miRNA-214, PDK1, phosphorylated Akt, mTOR, and mTORC1, was detected. These abnormalities were partially restored by XST treatment. Thus, XST ameliorated podocyte apoptosis partly through modulating the PTEN-PDK1-Akt-mTOR pathway. These novel findings might point the way to a natural therapeutic strategy for treating DKD.

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Protective effects ofSwietenia macrophyllaKing (seed & endocarp) aqueous-methanolic extract on pancreatic islet histology in streptozotocin-induced diabetic rats

Endocrine Abstracts ◽

10.1530/endoabs.32.p481 ◽

2013 ◽

Author(s):

Hanan Kumar Gopalan ◽

Nur Hayati Jafaar Marican ◽

Rahim Mhd Noah ◽

Rohani Mat Jais

Keyword(s):

Pancreatic Islet ◽

Methanolic Extract ◽

Diabetic Rats ◽

Protective Effects

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Hepato-renal protective effects of gallic acid and p-coumaric acid in nicotinamide/streptozotocin-induced diabetic rats

International Journal of Bioassays ◽

10.21746/ijbio.2016.06.0011 ◽

2016 ◽

Vol 5 (06) ◽

pp. 4641 ◽

Cited By ~ 5

Author(s):

Adel Abdel Moneim* ◽

Sanaa M. Abd El-Twab ◽

Mohamed B. Ashour ◽

Ahmed I. Yousef

Keyword(s):

Body Weight ◽

Gallic Acid ◽

Protein Profile ◽

Serum Glucose ◽

Diabetic Rats ◽

Hypoglycemic Agents ◽

Protective Effects ◽

Coumaric Acid ◽

Experimental Type

The goal of diabetes treatment is primarily to save life and alleviate symptoms and secondary to prevent long-term diabetic complications resulting from hyperglycemia. Thus, our present investigation was designed to evaluate the hepato-renal protective effects of gallic acid and p-coumaric acid in nicotinamide/streptozotocin (NA/STZ)-induced diabetic rats. Experimental type 2 diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (65 mg/kg b.wt.), after 15 min of i.p. injection of NA (120 mg/kg b.wt.). Gallic acid and p-coumaric acid were orally administered to diabetic rats at a dose of 20, 40 mg/kg b.wt./day, respectively, for 6 weeks. Body weight, serum glucose, protein profile, liver function enzymes and kidney function indicators was assayed. Treatment with either gallic acid or p-coumaric acid significantly ameliorated the elevated levels of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and uric acid. Both compounds were also found to restore total protein, albumin, and globulin as well as body weight of diabetic rats to near normal values. It can conclude that both gallic acid and p-coumaric acid have potent hypoglycemic and hepato-renal protective effects in diabetic rats. Therefore, our results suggest promising hypoglycemic agents that can attenuate the progression of diabetic hepatopathy and nephropathy.

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Hepato-protective effects of thymoquinone and beta-aminoisobutyric acid in streptozocin induced diabetic rats

Biotechnic & Histochemistry ◽

10.1080/10520295.2021.1949041 ◽

2021 ◽

pp. 1-10

Author(s):

İbrahim Aktaş ◽

Fatih Mehmet Gür

Keyword(s):

Diabetic Rats ◽

Protective Effects ◽

Aminoisobutyric Acid

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Protective Effects ofPanax notoginsengSaponins against High Glucose-Induced Oxidative Injury in Rat Retinal Capillary Endothelial Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/5326382 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 19

Author(s):

Yue Fan ◽

Yuan Qiao ◽

Jianmei Huang ◽

Minke Tang

Keyword(s):

Endothelial Cells ◽

Diabetic Retinopathy ◽

High Glucose ◽

Microvascular Dysfunction ◽

Panax Notoginseng ◽

Protective Effects ◽

Pronounced Increase ◽

Nadph Oxidase 4 ◽

Retinal Capillary ◽

Capillary Endothelial Cells

Diabetic retinopathy, a leading cause of visual loss and blindness, is characterized by microvascular dysfunction. Hyperglycemia is considered the major pathogenic factor for diabetic retinopathy and is associated with increased oxidative stress in the retina. In this study, we investigated the potential protective effects ofPanax notoginsengSaponins (PNS) in retinal capillary endothelial cells (RCECs) exposed to high glucose conditions. We found a pronounced increase in cell viability in rat RCECs incubated with both PNS and high glucose (30 mM) for 48 h or 72 h. The increased viability was accompanied by reduced intracellular hydrogen peroxide (H2O2) and superoxide (O2-), decreased mitochondrial reactive oxygen species (ROS), and lowered malondialdehyde (MDA) levels. PNS also increased the activities of total superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione peroxidase (GSH-PX). The glutathione (GSH) content also increased after PNS treatment. Furthermore, PNS reduced NADPH oxidase 4 (Nox4) expression. These results indicate that PNS exerts a protective effect against high glucose-induced injury in RCECs, which may be partially attributed to its antioxidative function.

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Attenuation of erythrocyte membrane oxidative stress bySesbania grandiflorain streptozotocin-induced diabetic rats

Biochemistry and Cell Biology ◽

10.1139/bcb-2015-0039 ◽

2015 ◽

Vol 93 (4) ◽

pp. 385-395 ◽

Cited By ~ 7

Author(s):

Chandrabose Sureka ◽

Thiyagarajan Ramesh ◽

Vavamohaideen Hazeena Begum

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Blood Glucose ◽

Erythrocyte Membrane ◽

Osmotic Fragility ◽

Diabetic Rats ◽

Glycosylated Haemoglobin ◽

Albino Rats ◽

Enzymatic Antioxidants ◽

Protective Effects

The aim of the present study was to investigate the protective effects of Sesbania grandiflora flower (SGF) extract on erythrocyte membrane in Streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 190–220 g, were made diabetic by an intraperitonial administration of STZ (45 mg/kg). Normal and diabetic rats were treated with SGF, and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In this study plasma insulin and haemoglobin levels were decreased and blood glucose, glycosylated haemoglobin, protein oxidation, lipid peroxidation markers, and osmotic fragility levels were increased in diabetic rats. Moreover, erythrocytes antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxide, glutathione reductase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase activities and non-enzymatic antioxidants such as vitamin C, vitamin E, reduced glutathione (GSH), and oxidized glutathione (GSSG) levels were altered. Similarly, the activities of total ATPases, Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase were also decreased in the erythrocytes of diabetic rats. Administration of SGF to STZ-induced diabetic rats reduced blood glucose and glycosylated haemoglobin levels with increased levels of insulin and haemoglobin. Moreover, SGF reversed the protein and lipid peroxidation markers, osmotic fragility, membrane-bound ATPases activities, and antioxidant status in STZ-induced diabetic rats. These results suggest that SGF could provide a protective effect on diabetes by decreasing oxidative stress-associated diabetic complications.

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