Background: Acetylshikonin, a major constituent isolated from Arnebia euchroma, is a potential candidate for anti-colorectal cancer drugs. However, the potential activity and underlying mechanism of Acetylshikonin aga...Background: Acetylshikonin, a major constituent isolated from Arnebia euchroma, is a potential candidate for anti-colorectal cancer drugs. However, the potential activity and underlying mechanism of Acetylshikonin against colorectal cancer remain unclear. Methods: In this study, Acetylshikonin was isolated from the active CHCl3 extract of Arnebia euchroma using activity-guided screening, and elucidated by the extensive spectroscopic analysis and comparison with literature data. Human colorectal cancer cells HT29, DLD-1, HCT116 or Caco-2 were exposed to different concentrations of Acetylshikonin (6.25 - 100 μg/mL) for 24 or 48 h. Cell viability, cell apoptosis and cell cycle distribution were detected. The activity of Acetylshikonin and potential mechanism of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway were evaluated in vitro and vivo. Results: We found that Acetylshikonin exhibited remarkable anti-proliferative activity in a dose-dependent manner against HT29 cells with the IC50 values of 60.82 μg/ml and 30.78 μg/ml at 24, 48 h, respectively. Moreover, Acetylshikonin induced cell cycle arrest at G0/G1 phase and early apoptosis through inhibition of PI3K/Akt/mTOR pathway. Furthermore, the assays of cell inhibition, early apoptosis and G0/G1 phase distribution showed that suppression of the PI3K/Akt pathway using LY294002 enhanced the anti-cancer effect of Acetylshikonin. Similarly, Acetylshikonin also decreased the growth of tumour in colorectal cancer xenografts in mice through PI3K/Akt/mTOR pathway. Conclusions: To sum up, these new findings provided a framework for further exploration of Acetylshikonin which possessed the potential antitumor activity by inhibiting PI3K/Akt/mTOR pathway.展开更多
[Objectives]This study was conducted to establish a mathematical model for supercritical CO_(2) extraction of curcumin.[Methods]With ginger as the experimental raw material,a quadratic polynomial mathematical model of...[Objectives]This study was conducted to establish a mathematical model for supercritical CO_(2) extraction of curcumin.[Methods]With ginger as the experimental raw material,a quadratic polynomial mathematical model of the yield of curcumin extracted by supercritical CO_(2) was established by response surface methodology(RSM).The validity of the mathematical model was verified,and the effects of extraction temperature(60-70℃),pressure(30-50 MPa)and time(70-90 min)on curcumin yield were analyzed.[Results]According to the model,the process parameters were optimized.Taking curcumin yield as the index,the optimal process conditions for supercritical CO_(2) extraction obtained were:temperature 62.6℃,pressure 37.7 MPa,time 82.9 min,under which the yield of curcumin was as high as 7.34%.Under the optimal extraction conditions,curcumin had a certain reducing capacity,and showed strong scavenging capacities to·OH,O_(2)^(-)·and DPPH,and its IC_(50) values were 9.40,9.03 and 8.04 mg/ml,respectively.Therefore,it is feasible to extract curcumin from ginger using supercritical CO_(2).[Conclusions]This study provides a theoretical basis for the development and utilization of curcumin.展开更多
文摘Background: Acetylshikonin, a major constituent isolated from Arnebia euchroma, is a potential candidate for anti-colorectal cancer drugs. However, the potential activity and underlying mechanism of Acetylshikonin against colorectal cancer remain unclear. Methods: In this study, Acetylshikonin was isolated from the active CHCl3 extract of Arnebia euchroma using activity-guided screening, and elucidated by the extensive spectroscopic analysis and comparison with literature data. Human colorectal cancer cells HT29, DLD-1, HCT116 or Caco-2 were exposed to different concentrations of Acetylshikonin (6.25 - 100 μg/mL) for 24 or 48 h. Cell viability, cell apoptosis and cell cycle distribution were detected. The activity of Acetylshikonin and potential mechanism of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway were evaluated in vitro and vivo. Results: We found that Acetylshikonin exhibited remarkable anti-proliferative activity in a dose-dependent manner against HT29 cells with the IC50 values of 60.82 μg/ml and 30.78 μg/ml at 24, 48 h, respectively. Moreover, Acetylshikonin induced cell cycle arrest at G0/G1 phase and early apoptosis through inhibition of PI3K/Akt/mTOR pathway. Furthermore, the assays of cell inhibition, early apoptosis and G0/G1 phase distribution showed that suppression of the PI3K/Akt pathway using LY294002 enhanced the anti-cancer effect of Acetylshikonin. Similarly, Acetylshikonin also decreased the growth of tumour in colorectal cancer xenografts in mice through PI3K/Akt/mTOR pathway. Conclusions: To sum up, these new findings provided a framework for further exploration of Acetylshikonin which possessed the potential antitumor activity by inhibiting PI3K/Akt/mTOR pathway.
基金Supported by National Science and Technology Support Program during the Twelfth Five-Year Plan(2011FJ1047).
文摘[Objectives]This study was conducted to establish a mathematical model for supercritical CO_(2) extraction of curcumin.[Methods]With ginger as the experimental raw material,a quadratic polynomial mathematical model of the yield of curcumin extracted by supercritical CO_(2) was established by response surface methodology(RSM).The validity of the mathematical model was verified,and the effects of extraction temperature(60-70℃),pressure(30-50 MPa)and time(70-90 min)on curcumin yield were analyzed.[Results]According to the model,the process parameters were optimized.Taking curcumin yield as the index,the optimal process conditions for supercritical CO_(2) extraction obtained were:temperature 62.6℃,pressure 37.7 MPa,time 82.9 min,under which the yield of curcumin was as high as 7.34%.Under the optimal extraction conditions,curcumin had a certain reducing capacity,and showed strong scavenging capacities to·OH,O_(2)^(-)·and DPPH,and its IC_(50) values were 9.40,9.03 and 8.04 mg/ml,respectively.Therefore,it is feasible to extract curcumin from ginger using supercritical CO_(2).[Conclusions]This study provides a theoretical basis for the development and utilization of curcumin.
