Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed a...Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice,and exploring the potential molecular mechanisms.Insulin resistance in mice was induced with a high fat diet for 16 weeks.Animals were then treated with three different doses of baicalin(100,200,and 400 mg·kg^(-1)·d^(-1)for 14 weeks.Fasting blood glucose,fasting serum insulin,glucose tolerance test(GTT),insulin tolerance test(ITT),and skeletal muscle lipid deposition were measured.Additionally,the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated.Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance.Moreover,insulin resistance was significantly reversed.Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle.The properties of baicalin were mediated,at least in part,by inhibition of the AMPK/ACC pathway,a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway,a key regulator of Glycogen synthesis.These data suggest that baicalin,at dose up to 400 mg·kg^(-1)·d^(-1),is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage,through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.展开更多
Berberis amurensis(Berberidaceae)is a traditional Chinese medicine,which is often used to treat hypertension,inflammation,dysentery and enteritis.It contains alkaloids,mainly including berberine,berbamine,magnoflorine...Berberis amurensis(Berberidaceae)is a traditional Chinese medicine,which is often used to treat hypertension,inflammation,dysentery and enteritis.It contains alkaloids,mainly including berberine,berbamine,magnoflorine,jatrorrhizine and palmatine.Berberis amurensis extracts(BAEs)is often orally taken.Oral herbs might be metabolized by intestinal bacteria in the small intestine.However,the interaction between the herb and the gut microbiota is still unknown.In the current study,UPLC/Q-TOFMS/MS combined with Metabolitepilot and Peakview software was used to identify the metabolites of BAEs in anti-biotic cocktail induced pseudo germ-free rats and normal rats.As a result,a total of 46 metabolites in normal rats were detected and its main metabolic pathways include demethylation,dehydrogenation,methylation,hydroxylation,sulfation and glucuronidation.Only 29 metabolites existed in pseudo germ-free rats.Dehydrogenated metabolites(M29,M30,M34 and M36),methylated metabolites(M33,M41 and M46)and other metabolites were not detected in pseudo germ-free rats.The result implied that the intestinal bacteria have an influence on the metabolism of BAEs.Furthermore,this investigation might contribute to the understanding of the metabolism of BAEs,and further promote its clinical application.展开更多
基金supported by a grant provided by Southeast University(No.9224007044)
文摘Insulin resistance is the pathophysiological basis of many diseases.Overcoming early insulin resistance highly significant in prevention diabetes,non-alcoholic fatty liver,and atherosclerosis.The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice,and exploring the potential molecular mechanisms.Insulin resistance in mice was induced with a high fat diet for 16 weeks.Animals were then treated with three different doses of baicalin(100,200,and 400 mg·kg^(-1)·d^(-1)for 14 weeks.Fasting blood glucose,fasting serum insulin,glucose tolerance test(GTT),insulin tolerance test(ITT),and skeletal muscle lipid deposition were measured.Additionally,the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated.Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance.Moreover,insulin resistance was significantly reversed.Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle.The properties of baicalin were mediated,at least in part,by inhibition of the AMPK/ACC pathway,a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway,a key regulator of Glycogen synthesis.These data suggest that baicalin,at dose up to 400 mg·kg^(-1)·d^(-1),is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage,through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.
基金supported by the National Key R&D Program of China(No.2018YFC1708203)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2018PT35031)+1 种基金the Drug Innovation Major Project(No.2018ZX09711001-002-002)the Major Science and Technology Project of Inner Mongolia Autonomous Region(No.2019ZD004).
文摘Berberis amurensis(Berberidaceae)is a traditional Chinese medicine,which is often used to treat hypertension,inflammation,dysentery and enteritis.It contains alkaloids,mainly including berberine,berbamine,magnoflorine,jatrorrhizine and palmatine.Berberis amurensis extracts(BAEs)is often orally taken.Oral herbs might be metabolized by intestinal bacteria in the small intestine.However,the interaction between the herb and the gut microbiota is still unknown.In the current study,UPLC/Q-TOFMS/MS combined with Metabolitepilot and Peakview software was used to identify the metabolites of BAEs in anti-biotic cocktail induced pseudo germ-free rats and normal rats.As a result,a total of 46 metabolites in normal rats were detected and its main metabolic pathways include demethylation,dehydrogenation,methylation,hydroxylation,sulfation and glucuronidation.Only 29 metabolites existed in pseudo germ-free rats.Dehydrogenated metabolites(M29,M30,M34 and M36),methylated metabolites(M33,M41 and M46)and other metabolites were not detected in pseudo germ-free rats.The result implied that the intestinal bacteria have an influence on the metabolism of BAEs.Furthermore,this investigation might contribute to the understanding of the metabolism of BAEs,and further promote its clinical application.
