chrysin and Insulin-Resistance

Diabetic nephropathy (DN) is a highly prevalent and severe diabetic complication. It is urgent to explore high efficiency and minor side effects therapy for DN. Chrysin is a natural flavonoid with various biological activities found in honey and propolis, and has considerable potential to improve DN. The study was designed to explore the effects and the specific underlying mechanism of chrysin for DN in high-fat-diet (HFD) and streptozotocin (STZ) induced DN mice. Firstly, the study revealed that chrysin effectively improved obesity, insulin resistance (IR), renal function, and pathological injury in DN mice. Secondly, the study found that chrysin improved the key indices and markers of lipid accumulation, oxidative stress, and inflammation which are closely related to the development or progression of DN. Moreover, chrysin markedly modulated lipid metabolism by regulating Adenosine 5' monophosphate-activated protein kinase (AMPK) and essential downstream proteins. Furthermore, AMPK inhibitor (Dorsomorphin) intervention partially suppressed the positive effects of chrysin on all testing indicators, indicating that activated AMPK is crucial for chrysin action on DN. The present study demonstrated that chrysin may improve DN by regulating lipid metabolism, and activated AMPK plays a critical role in the regulation of chrysin. PRACTICAL APPLICATIONS: The study verified the positive effects of chrysin on obesity, insulin resistance, kidney injury, renal function, lipid accumulation, inflammation, and oxidative stress, which are closely related to the development or progression of diabetic nephropathy (DN). Moreover, we explored that chrysin improves DN by regulating AMPK-mediated lipid metabolism. Furthermore, the AMPK inhibitor was used to confirm that activated AMPK plays a critical role in the effects of chrysin. These results could offer a full explanation and a potential option for adjuvant therapy of DN diabetes with chrysin.

Topics: AMP-Activated Protein Kinases; Animals; Diabetes Mellitus; Diabetic Nephropathies; Flavonoids; Inflammation; Insulin Resistance; Lipid Metabolism; Lipids; Mice; Streptozocin

Nuclear factor kappa B cells (NF-κB) activation causes induction of the noncanonical IκB kinases (I-kappa-B kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) in liver and fat after high fat diet which followed activating of cascade of counter-inflammation that conserves energy storage. Chrysin (5,7-dihydroxyflavone), a natural flavonoid, present in many plants, honey and propolis, used conventionally to treat numerous ailments. The present study was aimed to identify the protective role of chrysin on the glucose lowering and insulin sensitivity in diet induced obese (DIO) mice by regulating IKKε/TBK1. Chrysin administered therapeutically (60, 100, 200 mg/kg body weight) and preventive mode (200 mg/kg body weight) for 4 and 10 weeks respectively to DIO mice. At last fasting blood glucose, oral glucose tolerance test, serum lipid profile, as well as the expression level of IKKε/TBK1 and triglyceride in the liver tissue were assessed. DIO mice showed impaired glucose tolerance, reduced weight gain, elevated hepatic IKKε/TBK1 expression, fatty acid infiltration triglyceride and increased in plasma insulin and glucose. Chrysin in both therapeutic and preventive mode normalized the altered levels of the same. Overall chrysin improves glycemic control and insulin sensitivity through regulating expression of IKKε/TBK1 in liver of DIO mice.

Topics: Animals; Diet, High-Fat; Flavonoids; I-kappa B Kinase; Insulin Resistance; Liver; Mice; Mice, Obese; Protein Kinases; Protein Serine-Threonine Kinases

Natural products with minor side effects have been reported to be an effective adjuvant therapy for glucose and lipid metabolism disorders. Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective. This study was designed to explore the effects and mechanism of chrysin on metabolic syndrome using insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. The results indicated that chrysin significantly decreased insulin resistance, oxidative stress, inflammation, and liver injury. In addition, chrysin improved glycogen synthesis and fatty acid oxidation and inhibited gluconeogenesis and fatty acid synthesis by regulating GSK3β, G6Paes, PEPCK, SREBP1, FAS, and ACC1. Furthermore, the results of western blot and real-time PCR experiments demonstrated that chrysin modulated glucose and lipid metabolism through the AMPK/PI3K/AKT signaling pathway. Treatment with the AMPK inhibitor verified that AMPK activation is positively correlated with chrysin activity on glycolipid metabolism. This study confirms that chrysin is a potential treatment for glucose and lipid metabolism disorders.

Topics: AMP-Activated Protein Kinases; Animals; Flavonoids; Glucose; Hep G2 Cells; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Lipid Metabolism Disorders; Mice; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

Chrysin and luteolin are two flavonoids with Peroxisome proliferators-activated receptor γ (PPAR-γ) stimulating activity. Here, we investigated the protective effect of chrysin and luteolin from vascular complications associated with insulin resistance (IR). IR was induced in rats by drinking fructose for 12 weeks while chrysin and luteolin were given for 6 weeks with or without PPAR-γ antagonist, bisphenol A diglycidyl ether (BADGE). Then, blood pressure (BP) was recorded and serum levels of glucose, insulin, advanced glycation end products (AGEs) and lipids were measured. Concentration response curves for phenylephrine (PE), KCl, and acetylcholine (ACh) were obtained in thoracic aorta rings. Aortic reactive oxygen species (ROS) and nitric oxide (NO) generation were also studied. Chrysin and luteolin significantly alleviated systolic BP elevations caused by IR, while the co-administration of BADGE prevented chrysin alleviation. Although, neither chrysin nor luteolin affected ACh impaired vasodilatation, they both alleviated exaggerated vasoconstrictions to PE and KCl in IR animals. In addition, incubation of the aorta from IR animals with chrysin or luteolin prevented exaggerated vasoconstrictions to PE and KCl. On the other hand, co-administration of BADGE or co-incubation with GW9662, the selective PPAR-γ antagonist, prevented chrysin alleviation. Both chrysin and luteolin inhibited the developed hyperinsulinemia and increases in serum AGEs, lipids while, BADGE reduced the effect of chrysin on hyperinsulinemia and dyslipidemia. Chrysin and luteolin markedly inhibited elevated NO and ROS in IR aortae while BADGE did not change their effect on NO and ROS. In conclusion, chrysin and luteolin alleviate vascular complications associated with IR mainly through PPAR-γ dependent pathways.

Topics: Anilides; Animals; Aorta, Thoracic; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Epoxy Compounds; Flavonoids; Glycation End Products, Advanced; Hyperinsulinism; In Vitro Techniques; Insulin; Insulin Resistance; Lipids; Luteolin; Male; Muscle, Smooth, Vascular; Nitric Oxide; PPAR gamma; Rats; Reactive Oxygen Species; Vasoconstriction