Background Ursolic acid （UA） is a ubiquitous molecule in the plant kingdom with specific anticancer effects that have been shown in vitro and in vivo. Although UA can inhibit the proliferation of liver cancer cells ...Background Ursolic acid （UA） is a ubiquitous molecule in the plant kingdom with specific anticancer effects that have been shown in vitro and in vivo. Although UA can inhibit the proliferation of liver cancer cells and induce apoptosis of many types of tumor cells, the molecular mechanism of its anti-hepatoma activity is still not well defined. The objective of this study was to investigate the inhibitory effect and mechanisms of UA on the human hepatoma cell line SMMC-7721. Methods After treatment with UA, the growth inhibition of SMMC-7721 cells was assessed by MTT assay. Cells were also evaluated by flow cytometric analysis, Wright-Giemasa staining, Hoechst 33258 staining and transmission electron microscope after they were induced by UA. DNA microarray technology was used to investigate the gene expression pattern of SMMC-7721 cells exposed to UA 40 pmol/L. The molecular mechanism of cells death was analyzed by real-time RT-PCR and Western blotting. Results The proliferation of SMMC-7721 cells was significantly inhibited in a dose- and time-dependent manner after UA treatment. UA induced cell cycle arrest and apoptosis. The DNA microarray analysis indicated that 64 genes were found to be markedly up- or down-expressed, including GDF15, SOD2, ATF3, and fos. The result of Western blotting showed the apoptotic proteins p53 and Bax were up-regulated while the anti-apoptotic protein Bcl-2 was down-regulated. Real-time RT-PCR confirmed UA could up-regulate the mRNA expressions of GDF15, SOD2, ATF3 and down-regulate the mRAN expression of fos. Meanwhile these effects were partly blocked by pretreatment with the p53 inhibitor Pft-a. Conclusion Activation of the p53 pathway is involved in UA inhibition of SMMC-7721 human hepatocellular carcinoma cell growth and induction of apoptosis.展开更多
Background The effects of triterpenic acid from Prunella vulgaris L. （TAP） on diabetes and its mechanism are uncertain. The aim of this study was to investigate the effects of TAP on antihyperglycemic, antioxidant, ...Background The effects of triterpenic acid from Prunella vulgaris L. （TAP） on diabetes and its mechanism are uncertain. The aim of this study was to investigate the effects of TAP on antihyperglycemic, antioxidant, and pancreas-protective in streptozotozin （STZ）-diabetic rats. Methods The diabetic model was produced by injection of 60 mg/kg STZ. Blood was drawn from the tail vein of rats after 72 hours. Rats with blood glucose 〉16.7 mmol/L were considered diabetic. Diabetic rats were randomly divided into four groups： （1） Diabetes rat （STZ）, （2） Diabetic rats treated with 50 mg/kg of triterpenic acid from Prunella vulgaris L （STZ＋TAP50）, （3） Diabetic rats treated with 100 mg/kg TAP （STZ＋TAP100）, and （4） Diabetic rats treated with 200 mg/kg TAP （STZ＋TAP200）. Normal rats （n=10） acted as the control group （NC）. TAP was administered by the intragastric route once each day for six weeks. Body weight and the concentration of blood glucose （BG） were measured after three and six weeks. Fructosamine （FMN）, malondialdehyde （MDA）, and nitric oxide （NO）, and the activities of nitric oxide synthase （NOS） and superoxide dismutase （SOD） in serum were determined after six weeks using commercially available kits following the manufacturer＇s instructions. Pathologic changes in pancreatic β-cells were also investigated by microscopic examination after hematoxylin-eosin （HE） staining. The level of SOD mRNA in pancreatic β-cells was measured by polymerase chain reaction （PCR）. Results The levels of BG, FMN, NO, and MDA and the activities of NOS in serum in the four diabetes groups were significantly increased compared with the control group （P 〈0.01）. The activity of SOD in serum and the body weight was significantly decreased compared with the control group （P 〈0.01）. After administration of TAP to diabetic rats for six weeks, the body weight and the levels of BG, FMN, MDA, NO and the activity of NOS in serum decreased significantly compared with the STZ group in a dose-dependent manner. The activity of SOD in serum and body weight increased significantly compared with the STZ group in a dose-dependent manner. In addition, diabetic rats showed a significant decrease in SOD mRNA expression in pancreatic β cells. However, these changes were reversed by TAP. Histopathological examination also showed the protective effect of TAP on pancreatic β cells. Conclusions Triterpenic acid from Prunella vulgaris L. has an anti-diabetic effect, by controlling blood glucose and antioxidants, and has a protective effect on the pancreas.展开更多
文摘Background Ursolic acid （UA） is a ubiquitous molecule in the plant kingdom with specific anticancer effects that have been shown in vitro and in vivo. Although UA can inhibit the proliferation of liver cancer cells and induce apoptosis of many types of tumor cells, the molecular mechanism of its anti-hepatoma activity is still not well defined. The objective of this study was to investigate the inhibitory effect and mechanisms of UA on the human hepatoma cell line SMMC-7721. Methods After treatment with UA, the growth inhibition of SMMC-7721 cells was assessed by MTT assay. Cells were also evaluated by flow cytometric analysis, Wright-Giemasa staining, Hoechst 33258 staining and transmission electron microscope after they were induced by UA. DNA microarray technology was used to investigate the gene expression pattern of SMMC-7721 cells exposed to UA 40 pmol/L. The molecular mechanism of cells death was analyzed by real-time RT-PCR and Western blotting. Results The proliferation of SMMC-7721 cells was significantly inhibited in a dose- and time-dependent manner after UA treatment. UA induced cell cycle arrest and apoptosis. The DNA microarray analysis indicated that 64 genes were found to be markedly up- or down-expressed, including GDF15, SOD2, ATF3, and fos. The result of Western blotting showed the apoptotic proteins p53 and Bax were up-regulated while the anti-apoptotic protein Bcl-2 was down-regulated. Real-time RT-PCR confirmed UA could up-regulate the mRNA expressions of GDF15, SOD2, ATF3 and down-regulate the mRAN expression of fos. Meanwhile these effects were partly blocked by pretreatment with the p53 inhibitor Pft-a. Conclusion Activation of the p53 pathway is involved in UA inhibition of SMMC-7721 human hepatocellular carcinoma cell growth and induction of apoptosis.
文摘Background The effects of triterpenic acid from Prunella vulgaris L. （TAP） on diabetes and its mechanism are uncertain. The aim of this study was to investigate the effects of TAP on antihyperglycemic, antioxidant, and pancreas-protective in streptozotozin （STZ）-diabetic rats. Methods The diabetic model was produced by injection of 60 mg/kg STZ. Blood was drawn from the tail vein of rats after 72 hours. Rats with blood glucose 〉16.7 mmol/L were considered diabetic. Diabetic rats were randomly divided into four groups： （1） Diabetes rat （STZ）, （2） Diabetic rats treated with 50 mg/kg of triterpenic acid from Prunella vulgaris L （STZ＋TAP50）, （3） Diabetic rats treated with 100 mg/kg TAP （STZ＋TAP100）, and （4） Diabetic rats treated with 200 mg/kg TAP （STZ＋TAP200）. Normal rats （n=10） acted as the control group （NC）. TAP was administered by the intragastric route once each day for six weeks. Body weight and the concentration of blood glucose （BG） were measured after three and six weeks. Fructosamine （FMN）, malondialdehyde （MDA）, and nitric oxide （NO）, and the activities of nitric oxide synthase （NOS） and superoxide dismutase （SOD） in serum were determined after six weeks using commercially available kits following the manufacturer＇s instructions. Pathologic changes in pancreatic β-cells were also investigated by microscopic examination after hematoxylin-eosin （HE） staining. The level of SOD mRNA in pancreatic β-cells was measured by polymerase chain reaction （PCR）. Results The levels of BG, FMN, NO, and MDA and the activities of NOS in serum in the four diabetes groups were significantly increased compared with the control group （P 〈0.01）. The activity of SOD in serum and the body weight was significantly decreased compared with the control group （P 〈0.01）. After administration of TAP to diabetic rats for six weeks, the body weight and the levels of BG, FMN, MDA, NO and the activity of NOS in serum decreased significantly compared with the STZ group in a dose-dependent manner. The activity of SOD in serum and body weight increased significantly compared with the STZ group in a dose-dependent manner. In addition, diabetic rats showed a significant decrease in SOD mRNA expression in pancreatic β cells. However, these changes were reversed by TAP. Histopathological examination also showed the protective effect of TAP on pancreatic β cells. Conclusions Triterpenic acid from Prunella vulgaris L. has an anti-diabetic effect, by controlling blood glucose and antioxidants, and has a protective effect on the pancreas.
