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The aim of this study was to analyze the anti-cancer effect and mechanism of action of the flavonoids of Astragalus membranaceus (TFA) when combined with cisplatin on Lewis lung carcinoma-bearing mice. This animal experiment was approved by the Committee of the Ethics of Animal Experiment of Shanxi University (SXULL2018012). Pharmacological indices such as tumor weight, tumor volume growth curves, inhibition rate and organ indices showed that the TFA could reduce toxicity and enhance the efficacy of cisplatin. The target of TFA was predicted by network pharmacology analysis and the result showed that calycosin-7-O-β-D-glucoside might be the main active compound responsible for the anticancer effect of TFA. TRP53 (cellular tumor antigen p53), RAC1 (Ras-related C3 botulinum toxin substrate 1), ERBB2 (receptor tyrosine-protein kinase erbB-2), VEGFA (vascular endothelial growth factor A) and STAT3 (signal transducer and activator of transcription 3) may be associated with TFA in enhancing efficacy and reducing the toxicity of cisplatin. The IL-6 content in serum and expression levels of STAT3 and p53 in tumor tissues suggested that TFA may inhibit tumor growth through the IL-6/STAT3 pathway; UPLC-MS-based serum metabolomic analysis suggested that the metabolic pathways related to lung cancer include sphingolipid metabolism, retinol metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis, and the TFA-regulated corresponding pathway of bile acid biosynthesis. In this study, the anti-cancer effect and mechanism of action of TFA combined with cisplatin on Lewis lung carcinoma-bearing mice was analyzed by the combination of various techniques, which lay a foundation for further development of anticancer drugs.
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Objective To explore the effect of total flavonoids of astragalus (TFA) on the apoptosis of endothelial cells induced by serum of uremia patient .Methods The serum of 22 healthy volunteers and 25 uremia patients receiving regularly hemodialysis were enrolled in the study .HUVECs were used as research objects ,which were divided into control group(adding serum of healthy people when cell synchronized) and uremia group (adding serum of uremia patient when cell synchronized ) .Low dose ,moderate dose and high dose group were prepared by adding 0 .5 ,1 .0 ,2 .0 mg/mL TFA respectively 6 h before cell synchronization .After 24 hours′culture since the serum were added ,the morphological change of endothelial cells were observed by microscopy ,proliferation activities were tested by using MTT ,SOD activities were tested by using xanthine oxidase method ,NO levels were measured by u-sing nitrate reductase colorimetric method ,DNA damage was detected by using comet assay ,the morphological change of apoptosis was observed by using TUNEL method .Results Compared with the control group ,the proliferation activity ,SOD activity ,NO lev-els were lower in uremia group(P< 0 .01) ,DNA tailing rate ,apoptosis index(AI) significantly increased (P<0 .01) .Compared with cells of uremia group ,cell proliferation activity of all the TFA intervention groups increased (P<0 .05) ,NO levels also in-creased (P<0 .01) .Compared with uremia group ,moderate and high dose group′s SOD activity increased (P<0 .05) ,DNA damage tailing rate decreased (P<0 .05) .Conclusion Total flavonoids of astragalus reduces apoptosis of HUVECs induced by serum of uremia patient ,the possible mechanism is associated with the decrease of oxidative stress .
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Objective To investigate the different radioprotective effects of total flavonoids of Astragalus (TFA) on human normal mesenchymal stem cells(hMSCs) and hepatoma cells injured by 60 Coγ-ray radiation.Methods hMSCs and HepG-2 cells were cultured and randomly divided into TFA-treated and untreated groups.The cells of different groups were irradiated with 60 Co γ-rays at the dose of 6 Gy.MTT method was utilized to detect the survival rates of the hMSCs and HepG-2 cells pretreated or untreated with TFA before irradiation.Cell clone formation test was used to measure the cellular radiosensitivity.The apoptosis rates of different groups were determined by flow cytometer assay.The expression rates of the apoptosis-promoting proteins Fas and Bax and the apoptosis-inhibiting protein Bcl-2 were analyzed by Western blotting.Results MTT showed that the survival rates of hMSCs pretreated by TFA were 1.15-1.95 times higher than that of the pure irradiation group.On the contrary,the survival rates of the TFA pretreated HepG-2 cells were only 0.53-0.23 times that of the pure irradiation group.There was a good dose-effect relationship between the cell survival rate and the TFA concentration.Cell clone formation rate indicated that combined treatment of TFA and radiation inhibited the cell proliferation more effectively than single TFA or pure radiation.Flow cytometry showed that 6,24 and,48 h post-irradiation to 6 Gy,the apoptosis rates of the hMSCs were 23.3% ,11.2% ,and 2.9% ,respectively in the TFA pretreated group and were 29.3% ,24.9% ,and 13.6% in the pure radiation group.However,the apoptosis rates of the HepG-2 cells at 6,24,and 48 h post-irradiation to 6 Gy were 11.6% ,17.3% ,and 20.1% ,respectively in the TFA pretreated group and were 6.9% ,9.3% ,and 15.8% ,respectively in the direct radiation group.Western blotting showed that the expression levels of Fas and Bax proteins in the HepG-2 cells were significantly higher in the TFA pretreated group than in the pure radiation group.On the contrary,the expression level of the apoptosis inhibiting protein Bcl-2 was significantly lower in the TFA pretreated group than in the pure radiation group.Conclusions TFA has obvious effects of radiological protection on human hMSCs and has no effects of radiological protection but effects of apoptosis enhancement on hepatoma cells.The promotion of apoptosis of TFA on hepatoma cells is primarily through increasing the expression of apoptotic proteins such as Fas and Bax and reducing the expression of anti-apoptotic protein Bcl-2.
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Objective: To study the effects of total flavonoids of Astragalus on apoptosis of bovine retinal capillary pericytes(BRPs) under high glucose.Methods: The third generation of nearly symphysic bovine retinal vessel pericytes cultivated in vitro were divided into normal control group,high glucose group,and Astragalus total flavonoids groups(0.25,0.5,1.0,2.0 mg/ml) at random.After being incubated for 6 days,apoptosis of BRPs were detected by TUNEL method.TBA method was used to detect the contents of MDA.Xanthine oxidase method was used to detect the SOD activities.Results: Compared with high glucose group,the apoptosis,MDA contents,SOD activity,MDA content/SOD activity of BRPs reduced markedly in total flavonoids of Astragalus groups(0.5,1.0,2.0mg/ml)(P