Investigation determines the beneficial effect of bergaptol against gestational diabetes (GD). Gestational diabetes was induced in female rats and treated them with bergaptol 20 and 40 mg/kg for eighteen days. Effect of bergaptol was assessed on blood glucose and insulin level in GD rat. Inflammatory mediators and oxidative stress parameters were also assessed in GD rats. Moreover, mRNA expression of INSR, NF-kappaB, Akt and GSK-3beta were assessed in the GD rats by qRT-PCR method. In silico network pharmacology study was performed, along with gene ontology and egg pathway to assessed the targets of bergaptol, molecular docking study was also performed for the confirmation of possible pathway involved in the management of GD. Blood glucose and insulin level was significantly reduces in the blood bergaptol treated group than GD group of rats. Treatment with bergaptol ameliorates the altered level of mediators of inflammation and oxidative stress parameters in GD rats. There was significant reduction in the mRNA expression of NF-kappaB and GSK-3beta and increase in expression of INSR and Akt in the tissue homogenate of bergaptol treated GD rats. Docking study shows effective binding strength of bergaptol individually with INSR, NF-kappaB, Akt and GSK-3beta-protein targets. In conclusion, data of investigation suggest that bergaptol improves the sensitivity of insulin receptor in GD, as it reduces parameters of oxidative stress and inflammatory mediators by regulating INSR/NF-kappaB/Akt/GSK-3beta pathway. Key words Gestational diabetes, Bergaptol, Insulin resistance, Inflammation, Oxidative stress.

• MeSH
• experimentální diabetes mellitus * farmakoterapie   metabolismus   MeSH
• gestační diabetes * farmakoterapie   metabolismus   MeSH
• inzulinová rezistence * fyziologie   MeSH
• kinasa glykogensynthasy 3beta metabolismus   MeSH
• krevní glukóza metabolismus   účinky léků   MeSH
• krysa rodu rattus MeSH
• oxidační stres účinky léků   MeSH
• potkani Wistar MeSH
• receptor inzulinu metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• simulace molekulového dockingu * MeSH
• těhotenství MeSH
• zánět farmakoterapie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Up to now, there's a limited number of studies on the relationship between PINK1/Park2 pathway and mitophagy in NAFLD. To investigate the effect of Park2-mediated mitophagy on non-alcoholic fatty liver disease (NAFLD). Oleic acid was used for the establishment of NAFLD model. Oil red-dyed lipid drops and mitochondrial alternations were observed by transmission electron microscopy. Enzymatic kit was used to test lipid content. The levels of IL-8 and TNF-alpha were determined by ELISA. Lenti-Park2 and Park2-siRNA were designed to upregulate and downregulate Park2 expression, respectively. The changing expression of PINK and Park2 was detected by RT-qPCR and Western blot. Immunofluorescence staining was applied to measure the amount of LC3. Successful NAFLD modeling was featured by enhanced lipid accumulation, as well as the elevated total cholesterol (TC), triglyceride (TG), TNF-alpha and IL-8 levels. Mitochondria in NAFLD model were morphologically and functionally damaged. Park2 expression was upregulated by lenti-Park2 and downregulated through Park2-siRNA. The PINK1 expression showed the same trend as Park2 expression. Immunofluorescence staining demonstrated that the when Park2 was overexpressed, more LC3 protein on mitochondrial autophagosome membrane was detected, whereas Park2 knockdown impeded LC3' locating on the membrane. The transmission electron microscopy image exhibited that the extent of damage to the mitochondrial in NAFLD model was revered by enhanced Park2 expression but further exacerbated by reduced Park2 expression. Park2-mediated mitophagy could relive NAFLD and may be a novel therapeutic target for NAFLD treatment. Keywords: Non-alcoholic Fatty Liver Disease (NAFLD), Mitophagy, PINK1/Park2, Park2, PINK1.

• MeSH
• lidé MeSH
• mitofagie * fyziologie   MeSH
• myši MeSH
• nealkoholová steatóza jater * metabolismus   patologie   genetika   MeSH
• proteinkinasy * metabolismus   genetika   MeSH
• ubikvitinligasy * metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH