wogonin and Hyperglycemia

Protein kinase C (PKC) is a family of protein kinase enzymes that can phosphorylate other proteins and influence their functions, such as signal transduction, cell survival, and death. Increased diacylglycerol (DAG) concentrations, which are typically observed raised in hyperglycemic situations such as diabetes mellitus, can also activate PKC enzymes (DM). On the other hand, PKC isomers have been shown to play an essential role in diabetes and many hyperglycemic complications, most importantly atherosclerosis and diabetic cardiomyopathy (DCM). As a result, blocking PKC activation via DAG can prevent hyperglycemia and related consequences, such as DCM. Wogonin is a herbal medicine which has anti-inflammatory properties, and investigations show that it scavenge oxidative radicals, attenuate nuclear factor-kappa B (NF-κB) activity, inhibit several essential cell cycle regulatory genes, block nitric oxide (NO) and suppress cyclooxygenase- 2 (COX-2). Furthermore, several investigations show that wogonin also attenuates diacylglycerol DAG levels in diabetic mice. Since the DAG-PKC pathway is linked with hyperglycemia and its complications, Wogonin-mediated DAG-PKC attenuation can help treat hyperglycemia and its complications.

Topics: Animals; Atherosclerosis; Diabetic Cardiomyopathies; Diglycerides; Flavanones; Humans; Hyperglycemia; Protein Kinase C

Insulin resistance and type 2 Diabetes mellitus resulting in chronic hyperglycemia is a major health problem in the modern world. Many drugs have been tested to control hyperglycemia which is believed to be the main factor behind many of the diabetes-related late-term complications. Wogonin is a famous herbal medicine which has been shown to be effective in controlling diabetes and its complications. In our previous work, we showed that wogonin is beneficial in many ways in controlling diabetic cardiomyopathy. In this review, we mainly explained wogonin anti-hyperglycemic property through AKT/GLUT4 pathway. Here we briefly discussed that wogonin increases Glut4 trafficking to plasma membrane which allows increased entry of glucose and thus alleviates hyperglycemia. Conclusion: Wogonin can be used as an anti-diabetic and anti-hyperglycemic drug and works via AKT/GLUT4 pathway.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Flavanones; Glucose; Glucose Transporter Type 4; Humans; Hyperglycemia; Insulin; Insulin Resistance; Protein Transport; Proto-Oncogene Proteins c-akt

Wogonin has been reported to attenuate hyperglycemia in diabetic mice via anti-adipogenic effect on adipocytes. The potential therapeutic role of wogonin in nonalcoholic fatty liver disease (NAFLD) remains obscure. The aim of the present study was to explore the protective effect of wogonin on NAFLD mice and cultured NCTC 1469 cells exposed to palmitate. Wogonin supplementation significantly improved metabolic parameters in NAFLD mice, including body weight, blood glucose, insulin resistance, adiponectin, blood lipids, aminotransferases and hepatic histopathology. Further research in liver tissues from NAFLD mice and NCTC 1469 cells stressed by lipotoxicity showed wogonin treatment reduced inflammatory response by lowering interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), alleviated oxidative stress by preventing the accumulation of oxidative product malondialdehyde (MDA) and strengthening the anti-oxidative capacity of glutathione (GSH), Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPX). In addition, wogonin repaired the lipotoxicity-induced decline of peroxisome proliferator- activated receptor α (PPARα) and adiponectin receptor 2 (AdipoR2) in hepatocytes, in vivo and in vitro. Knock-down of PPARα abolished the protective effect of wogonin on NCTC 1469 cells, including the up-regulation of AdipoR2. Taken together, the current study demonstrated wogonin might be a potential therapeutic agent for NAFLD via up-regulation of hepatic PPARα/AdipoR2.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Diet, High-Fat; Flavanones; Gene Silencing; Hyperglycemia; Inflammation; Insulin Resistance; Liver; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oxidation-Reduction; Oxidative Stress; Palmitates; PPAR alpha; Protective Agents; Receptors, Adiponectin; Transaminases; Weight Gain

Among diabetic cardiovascular complications cardiomyopathy is major event which if not well controlled culminates in cardiac failure. Wogonin from the root of Scutellaria baicalensis Georgi has shown specific anti-diabetes bioactivity. However, its effect on diabetic complications remains unclear. The main purpose of this study is to investigate the potential effects of wogonin on diabetic cardiomyopathy and to figure out its underlying mechanism. We found that wogonin administration suppressed hyperglycemia, improved cardiac function, and mitigated cardiac fibrosis in STZ-induced diabetic mice. Wogonin supplementation also attenuated diabetic-induced cardiomyocyte apoptosis and necrosis. In addition, wogonin treatment exhibited the properties of anti-oxidative stress and anti-inflammation in STZ diabetic mice, evidenced by improved activities of anti-oxidases including SOD1/2 and CAT, decreased ROS and MDA production, suppressed expression of inflammation factors such as IL-1β, IL-6, TNFα, and PAI-1, and inhibited NF-κB signaling. These results suggested that wogonin potentially mitigate hyperglycemia-related cardiomyocyte impairment through inhibiting inflammation and oxidative stress.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Blood Glucose; Diabetic Cardiomyopathies; Fibrosis; Flavanones; Heart Function Tests; Hyperglycemia; Inflammation; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Necrosis; Organ Size; Oxidative Stress; Rats, Sprague-Dawley

Wogonin (5,7-dihydroxy-8-methoxyflavone), a major bioactive compound of the flavonoid family, is commonly extracted from the traditional Chinese medicine Scutellaria baicalensis and possesses antioxidant and anti-inflammatory activities and is assumed to have anti-diabetes function. Indeed, a current study has shown that it can possibly treat metabolic disorders such as those found in db/db mice. However, the underlying molecular mechanism remains largely unclear. The aim of this study was to investigate the impact of wogonin on osteopontin (OPN) expression in adipose tissue from type 1 diabetic mice and in 3T3-L1 adipocytes.. Type 1 diabetes was induced by streptozotocin (STZ) injection. 3T3-L1 preadipocytes were converted to 3T3-L1 adipocytes through treatment with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IBMX). Western blot analysis and RT-PCR were performed to detect protein expression and mRNA levels, respectively.. Wogonin treatment suppressed the increase in serum OPN levels and reduced OPN expression in adipose tissue from STZ-induced type 1 diabetic mice. Administration of wogonin enhanced PPARα expression and activity. Silencing of PPARα diminished the inhibitory effects of wogonin on OPN expression in 3T3-L1 adipocytes. Furthermore, the levels of c-Fos and phosphorylated c-Jun were reduced in wogonin-treated adipose tissue and 3T3-L1 adipocytes. In addition, wogonin treatment dramatically mitigated p38 MAPK phosphorylation. Pharmacological inhibition of p38 MAPK by its specific inhibitor SB203580 increased PPARα activity and decreased OPN expression.. Our results suggest that wogonin downregulated OPN expression in adipocytes through the inhibition of p38 MAPK and the sequential activation of the PPARα pathway. Given the adverse effects of high OPN levels on metabolism, our results provide evidence for the potential administration of wogonin as a treatment for diabetes.

Topics: 3T3-L1 Cells; Animals; Diabetes Mellitus, Type 1; Down-Regulation; Drugs, Chinese Herbal; Flavanones; Hyperglycemia; Mice; Mice, Inbred C57BL; Osteopontin; p38 Mitogen-Activated Protein Kinases; Phosphorylation; PPAR alpha; RNA Interference; RNA, Small Interfering; Scutellaria

Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis Gerogi. We evaluated the therapeutic effects of wogonin using db/db mice.. Mice received wogonin or vehicle by oral gavage for 2 weeks. Blood glucose, insulin, and cholesterol levels were measured, and liver morphology was observed with histopathological analysis. The mRNA expression levels of PPARα, PPARγ, and adiponectin in the liver and white adipose tissue (WAT) were determined by real-time PCR. Immunoblotting for AMPK and PPARγ, and adipocyte differentiation were investigated in vitro using 3T3-L1 cells. A luciferase assay was used to measure PPARα and PPARγ binding activity.. The wogonin group showed decreased weight gain without a change in food intake and improved glucose tolerance. Serum insulin and cholesterol levels in the wogonin group were significantly decreased compared to those in the control group. The wogonin group also showed less accumulation of lipid droplets and glycogen in the liver. PPARα and PPARγ expression levels in the liver and WAT and adiponectin expression level in WAT in the wogonin group were higher than those in the control group. In 3T3-L1 cells, wogonin was shown to stimulate AMPK activation in a dose-dependent manner. The presence of wogonin did not affect adipocyte differentiation or PPARγ protein level during adipogenesis. Notably, wogonin enhanced PPARα but not PPARγ transactivation.. These indicate that wogonin may have beneficial effects on glucose and lipid metabolism related to enhanced PPARα and adiponectin expression via AMPK activation. Importantly, wogonin did not cause deleterious effects, such as weight gain and fatty liver. Wogonin might be a useful therapeutic agent to treat type 2 diabetes.

Topics: 3T3-L1 Cells; Adipocytes; Adiponectin; Adipose Tissue, White; AMP-Activated Protein Kinases; Animals; Blood Glucose; Body Weight; Cell Differentiation; Cholesterol; Dyslipidemias; Flavanones; Gene Expression; Hyperglycemia; Insulin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; PPAR alpha; PPAR gamma