Ursolic acid induces U937 cells differentiation by PI3K/Akt pathway activation / 中国天然药物

AIM@#Ursolic acid (UA), a pentacyclic triterpenoid, is used as an anti-inflammatory and anti-cancer agent. There were few studies on the effects of UA on differentiation, and this is the first time to elucidate the potential effect and molecular mechanism of UA on inducing differentiation in the human leukemia cell line U937.@*METHODS@#Wright-Giemsa staining, nitroblue tetrazolium reduction assay and flow cytometric analysis were utilized to demonstrate the differentiation of U937 cells induced by UA. Western blotting and immunofluorescence assay were used to investigate the possible mechanism.@*RESULTS@#It was found that UA could induce the differentiation of U937cells and Akt-activity was significantly increased during differentiation. Additionally, LY294002, a PI3K-Akt inhibitor, could block the differentiation of U937 cells induced by UA.@*CONCLUSION@#UA could induce the differentiation of U937 cells by activating the PI3K/Akt pathway, and it could be a potential candidate as a differentiation-inducing agent for the therapy of leukemia.

Simultaneous determination of oleanolic acid and ursolic acid by RP-HPLC in the leaves of Eriobotrya japonica Lindl / 药物分析学报

Oleanolic acid (OA) and ursolic acid (UA) are isomeric triterpenic acids and only one methyl's position is different between them.OA and UA always exist in the same plant,so it is difficult to separate them when determining contents by RP-HPLC.In this study,a very simple mobile phase for HPLC was developed to simultaneously determine UA and OA,and the factors affecting separation were also discussed.The mobile phase is methanol:water (95∶5) with flow rate 0.4mL/min.The retention time for OA and UA was 20.58 and 21.57 min,respectively,the resolution was 1.61.The average contents of OA and UA of three Loquat leaves sets were 1.4 mg/g and 5.6 mg/g,respectively.Regarding the HPLC,we found that changing mobile phase,adjusting the pH value or adding ion-pairing agent could not affect the separation between UA and OA greatly.While adjustment of the flow rate and column temperature could improve the resolution greatly.

Absorption and transport mechanism of ursolic acid across Caco-2 monolayer model / 中草药

Objective To study the absorption and transport mechanism of ursolic acid(UA) by using Caco-2 monolayer model.Methods Evaluating the transport characteristic through studying whether P-glycoprotein(P-gp) transporter inhibitor Verapamil(VER) exists or not by using Caco-2 cell monolayer as an intestinal epithelial cell model and investigating the effects of uptake time,drug concentration,system temperature,and pH value of culture media on the uptake of UA.The drug concentration was measured by HPLC coupled with UV detector.Transport parameters and apparent permeability coefficients (P_(app)) were then calculated.Results In the concentration range of 10—40?mol/L,the uptake of UA by Caco-2 cell all linearly increased.The P_(app) of UA transported on Caco-2 cell monolayer model significantly changed when the specificity inhibitory of P-gp was added to model and the apparent permeability ratio decreased from 3.445 to 1.386.Conclusion The intestinal absorption of UA is passive diffusion as the dominating process and active transportation mediated by P-gp transporter in Caco-2 cell monolayer model.

Antitumor mechanism of ursolic acid on human gastric cancer cell lines SGC7901 in vitro / 中草药

Objective To investigate the potential mechanism of inhibition of ursolic acid(UA) on growth of human gastric cancer cell lines SGC7901 in vitro.Methods SGC7901 cells were cultured in vitro,MTT assay was used to observe the effect of UA on growth of SGC7901 cells in various concentrations for different times.After SGC7901 cells were treated by 0—40 ?mol/L UA for 24 h,morphological changes were observed by inverted microscope.Apoptotic changes were detected by fluorescence microscopy and flow cytometry (FCM).Protein expressions of Bcl-2 and Bax were determined by Western blotting.Results UA(20—40 ?mol/L) could significantly inhibit the growth of SGC7901 cells in a(dose-and) time-dependent manner,the IC_(50) value of UA for SGC7901 cells for 12,24,36,and 48 h were((57.50?)1.18),(34.28?2.05),(27.54?1.11),and(24.83?1.02) ?mol/L,respectively.After UA((20—)40 ?mol/L) treatment for 24 h,SGC7901 cells turned round and floated at different levels;SGC7901 cells were arrested at G_0/G_1 phase and apoptosis was induced,and the apoptotic rate was increased along with the increase of UA concentration.Meanwhile Bcl-2 protein expression decreased,whereas Bax protein expression unchanged.Conclusion UA has a stronger antitumor effect on SGC7901 cells.Cytotoxic effect,proliferation inhibition,and apoptosis may be involoved in the mechanism of UA,and the apoptosis caused by UA may be enhanced by decrease of Bcl-2 protein expression.