Objective: To determine whether corosolic acid(CA) targeting nuclear protein expression of Nrf2 activation can be used to attenuate renal damage and preserve renal function in alloxan diabetic mice.Methods: A mouse mo...Objective: To determine whether corosolic acid(CA) targeting nuclear protein expression of Nrf2 activation can be used to attenuate renal damage and preserve renal function in alloxan diabetic mice.Methods: A mouse model with diabetic nephropathy was established to examine the Nrf2 expression. Mice were randomly divided into control, diabetic control, and CA groups treated at 0.4 mg/kg, 2 mg/kg and 10 mg/kg p.o. for 8 weeks. Diabetes was induced in mice by single intraperitoneal injection of alloxan 200 mg/kg in all groups except the control. The mice with fasting blood glucose level over 200 mg/d L were considered as diabetic and were employed in the study. After 4 th and 8 th weeks, urine samples were collected(using metabolic cages) to measure protein and urea. Animals were euthanized, and serum samples were collected to estimate the glucose, creatinine, total protein, urea and blood urea nitrogen. Kidney was isolated at the end of experiment for histology to evaluate anti-oxidant parameters. Immunohistochemistry was performed to examine the Nrf2 expression.Results: CA treatment showed dose dependent reduction in level of biochemical parameters in serum and urine. CA group(10 mg/kg) showed significantly higher body weight and reduced kidney weight. Histopathological examination revealed reduced inflammation, collagen deposition and glomerulosclerosis in renal tissue. CA attenuated renal dysfunction, oxidative stress and inflammatory pro-cytokine levels.Conclusions: CA treatment exhibited ameliorative effect on kidney in mice with its enhanced Nrf2 expression.展开更多
2β,3α--Dihydroxyurs-12-en-28-oic acid （6） is a naturally occurring diastereoisomer of corosolic acid with glycogen phosphorylase inhibitory activity. A new strategy for the semi-synthesis of 6 was developed. Using...2β,3α--Dihydroxyurs-12-en-28-oic acid （6） is a naturally occurring diastereoisomer of corosolic acid with glycogen phosphorylase inhibitory activity. A new strategy for the semi-synthesis of 6 was developed. Using the commercially available ursolic acid （1） as the starting materials, 6 was synthesized through five facile reactions with a high stereoselectivity and an overall yield of 47,3%, The structure of 6 was confirmed by optical rotation, ESI-MS, 1H NMR and 13C NMR data,展开更多
基金the financial support received under University Grants Commission Minor Research Scheme with File no. 47-831/13(WRO), Pune
文摘Objective: To determine whether corosolic acid(CA) targeting nuclear protein expression of Nrf2 activation can be used to attenuate renal damage and preserve renal function in alloxan diabetic mice.Methods: A mouse model with diabetic nephropathy was established to examine the Nrf2 expression. Mice were randomly divided into control, diabetic control, and CA groups treated at 0.4 mg/kg, 2 mg/kg and 10 mg/kg p.o. for 8 weeks. Diabetes was induced in mice by single intraperitoneal injection of alloxan 200 mg/kg in all groups except the control. The mice with fasting blood glucose level over 200 mg/d L were considered as diabetic and were employed in the study. After 4 th and 8 th weeks, urine samples were collected(using metabolic cages) to measure protein and urea. Animals were euthanized, and serum samples were collected to estimate the glucose, creatinine, total protein, urea and blood urea nitrogen. Kidney was isolated at the end of experiment for histology to evaluate anti-oxidant parameters. Immunohistochemistry was performed to examine the Nrf2 expression.Results: CA treatment showed dose dependent reduction in level of biochemical parameters in serum and urine. CA group(10 mg/kg) showed significantly higher body weight and reduced kidney weight. Histopathological examination revealed reduced inflammation, collagen deposition and glomerulosclerosis in renal tissue. CA attenuated renal dysfunction, oxidative stress and inflammatory pro-cytokine levels.Conclusions: CA treatment exhibited ameliorative effect on kidney in mice with its enhanced Nrf2 expression.
基金Financial support from the Fundamental Research Funds for the Central Universities(No.DUT12JB08)
文摘2β,3α--Dihydroxyurs-12-en-28-oic acid （6） is a naturally occurring diastereoisomer of corosolic acid with glycogen phosphorylase inhibitory activity. A new strategy for the semi-synthesis of 6 was developed. Using the commercially available ursolic acid （1） as the starting materials, 6 was synthesized through five facile reactions with a high stereoselectivity and an overall yield of 47,3%, The structure of 6 was confirmed by optical rotation, ESI-MS, 1H NMR and 13C NMR data,
