Puerarin Mitigates Diabetic Hepatic Steatosis and Fibrosis by Inhibiting TGF-β Signaling Pathway Activation in Type 2 Diabetic Rats

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.

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Tangduqing Granules Attenuate Insulin Resistance and Abnormal Lipid Metabolism through the Coordinated Regulation of PPARγ and DGAT2 in Type 2 Diabetic Rats

Journal of Diabetes Research ◽

10.1155/2019/7403978 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Qinghua Zhang ◽

Yingying Huang ◽

Xiaojin Li ◽

Hongyi Liu ◽

Baichuan He ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Lipid Metabolism ◽

Insulin Sensitivity ◽

Fasting Blood Glucose ◽

Diabetic Rat ◽

Lipid Metabolism Disorder ◽

Metabolism Disorder ◽

Type 2 Diabetic

Insulin resistance (IR) is a vital hallmark of type 2 diabetes mellitus, which is characterized by an impaired ability of insulin to promote glucose uptake and utilization. Lipid deposition is closely associated with impaired insulin sensitivity. PPARγ plays an important role in glucose homeostasis, adipocyte differentiation, and insulin sensitivity. Likewise, DGAT2 also exerts a crucial role in integrating carbohydrate and lipid metabolism in the liver. The present study is aimed at evaluating a Chinese medicinal formula, Tangduqing granules (TDQ), with multifaceted actions against lipid and glucose metabolism disorder and IR of type 2 diabetes. An animal model of type 2 diabetes was developed by high-fat diet feeding plus low-dose streptozotocin injection. After oral administration of TDQ for 5 weeks, the effects on glucose and lipid metabolism and the underlying mechanism were evaluated by biochemical, histological, RT-PCR, and western blotting methods. The results showed that TDQ decreased fasting blood glucose, ameliorated glucose tolerance, and improved IR. Besides, TDQ regulated hyperlipidemia symptoms, decreased serum lipid levels and liver TG, and reduced hepatic steatosis in a type 2 diabetic rat model. Furthermore, TDQ reversed diabetes-induced decrease in the mRNA and protein expression of PPARγ and elevation in the mRNA and protein levels of DGAT2 in the liver. In addition, we showed that interference of TDQ ameliorated palmitate-induced glucose and lipid metabolic abnormalities in HepG2 cells. TDQ are, therefore, a potential Chinese medicinal formula that relieves IR and lipid metabolism disorder might be through promotion of PPARγ and decrease of DGAT2 expression.

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Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway

PLoS ONE ◽

10.1371/journal.pone.0152097 ◽

2016 ◽

Vol 11 (3) ◽

pp. e0152097 ◽

Cited By ~ 37

Author(s):

Shengnan Wei ◽

Ming Zhang ◽

Yang Yu ◽

Xiaoxin Lan ◽

Fan Yao ◽

...

Keyword(s):

Lipid Metabolism ◽

Hepg2 Cells ◽

Diabetic Mice ◽

Hepatic Gluconeogenesis ◽

Lipid Metabolism Disorder ◽

Metabolism Disorder ◽

Type 2 Diabetic

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

Journal of Diabetes Research ◽

10.1155/2016/2641248 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 29

Author(s):

Li-ping Han ◽

Chun-jun Li ◽

Bei Sun ◽

Yun Xie ◽

Yue Guan ◽

...

Keyword(s):

Liver Injury ◽

Signaling Pathway ◽

Diabetic Rats ◽

Inflammatory Factors ◽

Hepatic Tissue ◽

Control Group ◽

Dependent Manner ◽

Protective Effects ◽

Type 2 Diabetic

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.

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Scutellarin Reduce the Homocysteine Level and Alleviate Liver Injury in Type 2 Diabetes Model

Frontiers in Pharmacology ◽

10.3389/fphar.2020.538407 ◽

2020 ◽

Vol 11 ◽

Author(s):

Yiyu Wang ◽

Xiaoming Fan ◽

Biao Fan ◽

Kerong Jiang ◽

Haoxin Zhang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Liver Injury ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Diabetic Rats ◽

Lipid Metabolism Disorder ◽

Metabolism Disorder ◽

Diabetes Model ◽

Induced Apoptosis

Scutellarin (SCU) is an active ingredient extracted from Erigeron breviscapus (Vaniot) Hand.-Mazz. Its main physiological functions are anti-inflammatory and antioxidant. In this study, we established a STZ-induced model of type 2 diabetes (T2DM) and a homocysteine (Hcy)-induced apoptosis model of LO2 to investigate whether SCU can alleviate liver damage by regulating Hcy in type 2 diabetes. Biochemical analysis indicated that SCU could improve the lipid metabolism disorder and liver function in diabetic rats by downregulating the levels of triglycerides (TG), cholesterol (CHO), low-density lipoprotein (LDL), alanine transaminase (ALT) and aspartate transaminase (AST), and by upregulating the level of high-density lipoprotein (HDL). Interestingly, SCU also could down-regulate the levels of Hcy and insulin and enhance the ability of type 2 diabetic rats to regulate blood glucose. Mechanistically, our results indicated that SCU may control the level of Hcy through regulating the levels of β-Cystathionase (CBS), γ-Cystathionase (CSE) and 5,10-methylenetetrahydrofolate (MTHFR) in liver tissue, and up-regulate folic acid, VitB6 and VitB12 levels in serum. Furthermore, SCU inhibits apoptosis in the liver of T2DM rats and in cultured LO2 cells treated with Hcy. Together, our findings suggest that SCU may alleviate the liver injury thorough downregulating the level of Hcy in T2DM rats.

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