scholarly journals Protective Effects of Celastrol on Diabetic Liver Injury via TLR4/MyD88/NF-κB Signaling Pathway in Type 2 Diabetic Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Li-ping Han ◽  
Chun-jun Li ◽  
Bei Sun ◽  
Yun Xie ◽  
Yue Guan ◽  
...  

Immune and inflammatory pathways play a central role in the pathogenesis of diabetic liver injury. Celastrol is a potent immunosuppressive and anti-inflammatory agent. So far, there is no evidence regarding the mechanism of innate immune alterations of celastrol on diabetic liver injury in type 2 diabetic animal models. The present study was aimed at investigating protective effects of celastrol on the liver injury in diabetic rats and at elucidating the possible involved mechanisms. We analyzed the liver histopathological and biochemical changes and the expressions of TLR4 mediated signaling pathway. Compared to the normal control group, diabetic rats were found to have obvious steatohepatitis and proinflammatory cytokine activities were significantly upregulated. Celastrol-treated diabetic rats show reduced hepatic inflammation and macrophages infiltration. The expressions of TLR4, MyD88, NF-κB, and downstream inflammatory factors IL-1βand TNFαin the hepatic tissue of treated rats were downregulated in a dose-dependent manner. We firstly found that celastrol treatment could delay the progression of diabetic liver disease in type 2 diabetic rats via inhibition of TLR4/MyD88/NF-κB signaling cascade pathways and its downstream inflammatory effectors.

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Biyu Hou ◽  
Yuerong Zhao ◽  
Guifen Qiang ◽  
Xiuying Yang ◽  
Chunyang Xu ◽  
...  

Lipid metabolism disorder and inflammation are essential promoters in pathogenesis of liver injury in type 2 diabetes. Puerarin (PUR) has been reported to exert beneficial effects on many diabetic cardiovascular diseases and chemical-induced liver injuries, but its effects on diabetic liver injury and its mechanism are still unclear. The current study was designed to explore the therapeutic effect and mechanism of PUR on liver injury in a type 2 diabetic rat model induced by a high-fat diet combined with low-dose streptozotocin. The diabetic rats were treated with or without PUR (100 mg/kg/day) by gavaging for 8 weeks, and biochemical and histological changes in liver were examined. Results showed that treatment with PUR significantly attenuated hepatic steatosis by regulating blood glucose and ameliorating lipid metabolism disorder. Liver fibrosis was relieved by PUR treatment. PUR inhibited oxidative stress and inflammation which was associated with inactivation of NF-κB signaling, thereby blocking the upregulation of proinflammatory cytokines (IL-1β, TNF-α) and chemokine (MCP-1). This protection of PUR on diabetic liver injury is possibly related with inhibition on TGF-β/Smad signaling. In conclusion, the present study provides evidence that PUR attenuated type 2 diabetic liver injury by inhibiting NF-κB-driven liver inflammation and the TGF-β/Smad signaling pathway.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lishan Zhou ◽  
Hui Dong ◽  
Yi Huang ◽  
Lijun Xu ◽  
Xin Zou ◽  
...  

Hu-Lu-Ba-Wan (HLBW) is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN) in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and protein kinase C-alpha (PKC-α) related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47phox, and the protein expression of phosphorylated PKC-αin renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-α/NADPH oxidase signaling pathway.


2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.


2014 ◽  
Vol 66 ◽  
pp. 358-365 ◽  
Author(s):  
Gopalsamy Rajiv Gandhi ◽  
Pautu Vanlalhruaia ◽  
Antony Stalin ◽  
Santiagu Stephen Irudayaraj ◽  
Savarimuthu Ignacimuthu ◽  
...  

2019 ◽  
Vol 72 (1-2) ◽  
pp. 1900203
Author(s):  
Liyan Zhao ◽  
Qifang Zheng ◽  
Yalu Zou ◽  
Yuanyuan Wang ◽  
Yuntang Wu ◽  
...  

2019 ◽  
Vol 6 (1) ◽  
pp. 15-23
Author(s):  
Kazuki Mochizuki ◽  
Yu Tan ◽  
Yumiko Uchiyama ◽  
Takuji Suzuki ◽  
Natsuyo Hariya ◽  
...  

Nutrition ◽  
2015 ◽  
Vol 31 (5) ◽  
pp. 733-739 ◽  
Author(s):  
Ze-Qiang Ren ◽  
Peng-Bo Zhang ◽  
Xiu-Zhong Zhang ◽  
Shou-Kun Chen ◽  
Hong Zhang ◽  
...  

2017 ◽  
Vol 42 (4) ◽  
pp. 377-383 ◽  
Author(s):  
Chika Ifeanyi Chukwuma ◽  
Md. Shahidul Islam

Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC50= 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU50= 3.5% ± 1.6%) or without insulin (GU50= 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.


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