Oleanolic acid(OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970 s. In our...Oleanolic acid(OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970 s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks(4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 m RNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 m RNAs were up-regulated and 4 m RNAs were down-regulated significantly after OA treatment. Five m RNAs(CACNA1 B, FCN, STEAP3, AMPH, and NR6 A1) were selected to validate the expression levels by q RT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.展开更多
AIM: To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid(MA) exerts anti-diabetic effects. METHOD: HepG2 cells were stimulated with various concentrations ...AIM: To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid(MA) exerts anti-diabetic effects. METHOD: HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a(GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β(IRβ), protein kinase B(also known as Akt), and glycogen synthase kinase-3β(GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay(ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet(HFD). RESULTS: The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content. CONCLUSION: The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.展开更多
The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) i...The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) in GK rats was examined.GK rats receiving AA at a daily dose of 25 mg·kg-1 for four weeks showed a significant reduction in blood glucose levels.Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose(CMC-Na) solution for the same periods and used as control.Compared to the normal Wistar rats,GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level(P < 0.01) and insulin level(P < 0.05).Furthermore,the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats.Fibronectin,a key protein related to islet fibrosis,was over-expressed in GK rats,which was reversed significantly by AA treatment(P < 0.05).These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes,which may play a role in the prevention of islets展开更多
Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction(MI),by far,there are few preventive and therapeutic options for ischemic heart failure(IHF)after MI.Qi-Tai...Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction(MI),by far,there are few preventive and therapeutic options for ischemic heart failure(IHF)after MI.Qi-Tai-Suan(QTS)is an oleanolic acid(OA)derivative which once underwent a clinical trial for treating hepatitis.In this study,we investigated the potential cardioprotective effect of QTS on IHF.IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice,and the protective effects of QTS on IHF were examined by echocardiography measurement,histological and TUNEL analysis,etc.We found that QTS exhibited promising cardioprotective effect on IHF.QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure.Notably,QTS had much better oral bioavailability(F=41.91%)in mice than its parent drug OA,and took effects mainly as its original form.Mechanistically,QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis,inflammation and fibrosis.Taken together,QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.展开更多
基金supported by National Natural Science Foundation of China(Nos.81673443,81373303 and 31501182)by the Fundamental Research Funds for the Central Universities(No.26302017ZD05)
文摘Oleanolic acid(OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970 s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks(4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 m RNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 m RNAs were up-regulated and 4 m RNAs were down-regulated significantly after OA treatment. Five m RNAs(CACNA1 B, FCN, STEAP3, AMPH, and NR6 A1) were selected to validate the expression levels by q RT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.
基金supported by the FundamentalResearch Funds for the Central Universities(No.JKP2011004)
文摘AIM: To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid(MA) exerts anti-diabetic effects. METHOD: HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a(GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β(IRβ), protein kinase B(also known as Akt), and glycogen synthase kinase-3β(GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay(ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet(HFD). RESULTS: The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content. CONCLUSION: The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.
基金supported by the Fundamental Research Funds for the Central Universities(No.JKP2011004)
文摘The Goto-Kakizaki(GK) rat is a spontaneous type 2 diabetic animal model,which is characterized by a progressive loss of beta islet cells with fibrosis.In the present study,the hypoglycemic effect of asiatic acid(AA) in GK rats was examined.GK rats receiving AA at a daily dose of 25 mg·kg-1 for four weeks showed a significant reduction in blood glucose levels.Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose(CMC-Na) solution for the same periods and used as control.Compared to the normal Wistar rats,GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level(P < 0.01) and insulin level(P < 0.05).Furthermore,the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats.Fibronectin,a key protein related to islet fibrosis,was over-expressed in GK rats,which was reversed significantly by AA treatment(P < 0.05).These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes,which may play a role in the prevention of islets
基金This program was financially supported by the National Natural Science Foundation of China(Nos.81730094 and 91853125).
文摘Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction(MI),by far,there are few preventive and therapeutic options for ischemic heart failure(IHF)after MI.Qi-Tai-Suan(QTS)is an oleanolic acid(OA)derivative which once underwent a clinical trial for treating hepatitis.In this study,we investigated the potential cardioprotective effect of QTS on IHF.IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice,and the protective effects of QTS on IHF were examined by echocardiography measurement,histological and TUNEL analysis,etc.We found that QTS exhibited promising cardioprotective effect on IHF.QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure.Notably,QTS had much better oral bioavailability(F=41.91%)in mice than its parent drug OA,and took effects mainly as its original form.Mechanistically,QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis,inflammation and fibrosis.Taken together,QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.
