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EWS Knockdown and Taxifolin Treatment Induced Differentiation and Removed DNA Methylation from p53 Promoter to Promote Expression of Puma and Noxa for Apoptosis in Ewing’s Sarcoma 被引量:2
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作者 Mohammad Motarab Hossain Swapan Kumar Ray 《Journal of Cancer Therapy》 2014年第12期1092-1113,共22页
Ewing’s sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing’s sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression... Ewing’s sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing’s sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing’s sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing’s sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing’s sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing’s sarcoma in cell culture and animal models. 展开更多
关键词 APOPTOSIS Differentiation Ewing’s Sarcoma EWS shRNA P53 PROMOTER taxifolin
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Fabrication of taxifolin loaded zein-caseinate nanoparticles and its bioavailability in rats 被引量:1
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作者 Ying Li Hang Su +4 位作者 Wenjun Wang Zhongping Yin Jing’en Li En Yuan Qingfeng Zhang 《Food Science and Human Wellness》 SCIE CSCD 2023年第6期2306-2313,共8页
Taxifolin loaded zein-caseinate nanoparticles(TZP)were fabricated by the anti-solvent method and were used as an oral delivery vehicle to improve their bioavailability in the rat.The formulations of TZP were optimized... Taxifolin loaded zein-caseinate nanoparticles(TZP)were fabricated by the anti-solvent method and were used as an oral delivery vehicle to improve their bioavailability in the rat.The formulations of TZP were optimized.With mass ratio of 1:1:2 between taxifolin,zein and sodium caseinate,the particle size andζpotential of TZP were(168.74±0.35)nm and−(57.67±0.25)mV,while the encapsulation and loading efficiency of taxifolin were(85.83±0.89)%and(17.11±0.88)%,respectively.After freeze-drying,TZP exhibited excellent redispersibility in water without aggregation.Physicochemical characterization showed that taxifolin existed in amorphous form in TZP and its interaction with the protein was observed.After encapsulating in TZP,the excellent dispersion of taxifolin in water signifi cantly improve its diffusion velocity through a semipermeable membrane.After oral administration,taxifolin and its 5 metabolites were identifi ed in rat plasma by ultra high performance liquid chromatography(UPLC)with quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS).The dynamic variation of taxifolin and its metabolites in plasma were then quantifi ed by UPLC with a triple-quadrupole typemass spectroscopy(UPLC-QqQ-MS/MS).A pharmacokinetic study showed that the bioavailability of taxifolin increased from 0.35%to 0.52%through TZP fabrication.The plasma concentration of taxifolin glucuronide and methylated taxifolin glucuronide was much higher than taxifolin.Glucuronidation was the dominating metabolism pathway of taxifolin in vivo. 展开更多
关键词 taxifolin Zein nanoparticles Characterization BIOAVAILABILITY
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Taxifolin protects hypoxia-induced cardiomyocytes injury via HIF1-a/HO-1/autophagy pathway 被引量:2
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作者 林骏 谢庆 +5 位作者 赵明一 庄建 陈志衡 蔡骞 叶艳琼 朱平 《South China Journal of Cardiology》 CAS 2017年第2期150-156,共7页
Background Autophagy, a dynamic and efficient process of self-digestion in vivo, has been proven to be ben- eficial for cardiac protection during MI process via removing the additional protein and damaged organelles i... Background Autophagy, a dynamic and efficient process of self-digestion in vivo, has been proven to be ben- eficial for cardiac protection during MI process via removing the additional protein and damaged organelles in the heart. Taxifolin (Tax), a common plant flavonoid, has been widely used for the treatment of myocardial infarction. However, the underlying mechanism of Tax is largely unknown. Methods Murine arterial cardiomyocytes HL-1 cells were pretreated with Tax and then exposed to hypoxia environment. CCK-8 was performed for the de- termination of cell viability. Monodansylcadaverine (MDC) and Microtubule-associated protein 1A/1B-light chain 3 (LC3) were analyzed by immunofluorescence staining. The relative gene expressions of Hypoxia Inducible Factor-1 (HIFI-a) and Heine Oxygenase-1 (HO-1) were determined by qRT-PCR. Results Tax at 100μm for 6 h has the maximal effect to avoid reducing the cell viability excessively and significantly abolished hypoxia-induced cell death. Both of the MDC and LC3 immunofluorescence staining revealed markedly increase of expression of autophagy with pretreatment of Tax. Finally, qRT-PCR showed the upregulation of HIFI-a and HO-1 with Tax. Conclusions Taken together, Tax might be a potential candidate for the treatment of MI by promoting cardio- myocyte autophagy via the activation of HIF 1-a and HO-1. 展开更多
关键词 taxifolin AUTOPHAGY HIFI-a HO-1
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Taxifolin attenuates ischemia-reperfusion induced oxidative ovarian damage in rats
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作者 Sevil Kiremitli Tunay Kiremitli +7 位作者 Umit Nayki Nesrin Yilmaz Can Turkler Kemal Dinc Renad Mammadov Gulce Naz Yazici Mine Gulaboglu Nihal Cetin 《Asian pacific Journal of Reproduction》 2021年第4期168-175,共8页
Objective:To investigate preventive effects of taxifolin on ischemia-reperfusion induced oxidative ovarian damage in rats.Methods:A total of 18 female Wistar albino rats were randomly and equally divided into three gr... Objective:To investigate preventive effects of taxifolin on ischemia-reperfusion induced oxidative ovarian damage in rats.Methods:A total of 18 female Wistar albino rats were randomly and equally divided into three groups:the sham group,the ovarian ischemia reperfusion group,and the 50 mg/kg taxifolin+ovarian ischemia reperfusion group.The ovarian ischemia reperfusion and taxifolin+ovarian ischemia reperfusion groups were exposed to ischemia for 2 h and then followed by two-hour reperfusion protocol.Biochemical and histopathologic examinations were performed on the extracted ovaries.Results:Levels of malondialdehyde and cyclooxygenase-2 were increased,while reduced-glutathione and cyclooxygenase-1 were decreased in the ovarian ischemia reperfusion group.However,these values were reversed in the taxifolin+ovarian ischemia reperfusion group.Similarly,the number of primordial and developing follicules decreased in the ovarian ischemia reperfusion group,while they were within normal range in the taxifolin+ovarian ischemia reperfusion group.Conclusions:Ischemia followed by reperfusion leads to oxidative stress-related ovarian injury,and taxifolin may be useful for protecting ovarian tissue from such injury. 展开更多
关键词 ANTIOXIDANTS ISCHEMIA-REPERFUSION Ovarian damage Rat taxifolin Oxidative stress Ovarian torsion
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Effect of taxifolin on cold-shock damages in spermatozoa in rabbits
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作者 Irfan Yılmaz Gaffari Turk +4 位作者 Aslıhan Cakir Cihangiroglu Tutku Can Acisu Ibrahim Halil Gungor GozdeArkali Edanur Guler Ekmen 《Asian pacific Journal of Reproduction》 2023年第5期239-248,共10页
Objective:To investigate the effect of taxifolin added to rabbit semen on freezing-induced cold-shock damages in spermatozoa.Methods:Semen was collected from six adult New Zealand rabbits once a week by artificial vag... Objective:To investigate the effect of taxifolin added to rabbit semen on freezing-induced cold-shock damages in spermatozoa.Methods:Semen was collected from six adult New Zealand rabbits once a week by artificial vagina.The collected semen was pooled at 38℃ and divided into four equal volumes.They were diluted with 0,50,100 and 200μM taxifolin-containing Tris+egg yolk extender at 38℃ and their temperatures were lowered to 4℃.Following equilibration,semen drawn into 0.25 mL straws were frozen in an automatic semen freezing device and stored in liquid nitrogen container at-196℃.Samples were thawed in 38℃ water for 25 s and the analyses of motility,kinematic parameters,morphological deformities,changes in membrane integrity,mitochondrial membrane potential,dead-live ratio,acrosomal damages and as well as oxidative stress analyses were performed in semen.Results:Addition of 50μM taxifolin significantly improved motility(total,progressive,rapid and static),high mitochondrial membrane potential and the ratios of spermatozoa with acrosomal damage compared to the control group.Compared to the control group,malondialdehyde(MDA)levels in the 50 and 100μM taxifolin groups were significantly lower,while the MDA level was high and viable spermatozoa ratio was low in the 200μM taxifolin group.There were no significant differences between the groups in terms of kinematic parameters,morphological deformities,membrane integrity and antioxidant levels.Conclusions:The low dose of taxifolin(50μM)has a positive effect and the high dose(200μM)has a negative effect.Therefore,it is concluded that the addition of low-dose(50μM)taxifolin to the extenders would be a useful additive in reducing cold-shock damage that occurs during freezing of rabbit semen. 展开更多
关键词 taxifolin Semen freezing COLD-SHOCK Oxidative stress Rabbit
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Protective effects of Taxifolin on H_2O_2-induced damage in H9C2 cells
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作者 HUANG Jun-gang ZHAO Ming-yi +4 位作者 WANG Xiao-li SU Qi-li CAI Qian LI Peng ZHU Ping 《South China Journal of Cardiology》 CAS 2017年第3期209-214,共6页
Background Taxifolin(Tax) is an essential natural antioxidant. Multiple studies have shown that Tax can protect cardiomyocytes from ischemia-reperfusion injury. However, the underlying mechanism is still unclear.Met... Background Taxifolin(Tax) is an essential natural antioxidant. Multiple studies have shown that Tax can protect cardiomyocytes from ischemia-reperfusion injury. However, the underlying mechanism is still unclear.Methods H9C2 cells were randomly divided into control, H_2O_2 group, Tax pretreatment group(Tax + H_2O_2);Tax effect group. Cell activity was detected by CCK-8 and the intracellular structure was observed by transmission electron microscopy. Autophagy was determine by Western blotting analysis of Beclin-1, Bcl-2 and PKC.Results Tax pretreatment significantly increased anti-apoptotic protein Bcl-2 and autophagy protein Beclin-1.Expression of PKC was inhibited by Tax. Conclusions Tax pretreatment could protect H9 C2 cells against H_2O_2-induced damage through the Bcl-2 and autophagy pathways. 展开更多
关键词 taxifolin AUTOPHAGY PKC pathway anti-oxidative effect.
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Taxifolin和EGCG对IFN-γ诱导的HaCaT细胞iNOS表达的影响
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作者 伍春莲 《西华师范大学学报(自然科学版)》 2012年第3期256-260,共5页
紫杉叶素和L-(-)-表没食子儿茶素没食子酸酯(EGCG)均属于类黄酮物质,具有抗炎活性.本文采用激光共聚焦显微镜和流式细胞仪检测SMT(iNOS抑制子)对800U/mL IFN-γ诱导的iNOS表达的影响,结果发现人表皮角质细胞HaCaT中800U/mL IFN-γ诱导i... 紫杉叶素和L-(-)-表没食子儿茶素没食子酸酯(EGCG)均属于类黄酮物质,具有抗炎活性.本文采用激光共聚焦显微镜和流式细胞仪检测SMT(iNOS抑制子)对800U/mL IFN-γ诱导的iNOS表达的影响,结果发现人表皮角质细胞HaCaT中800U/mL IFN-γ诱导iNOS蛋白的表达显著提高,同时SMT可以抑制IFN-γ诱导iNOS蛋白的表达.分别用40μg/mL紫杉叶素和40μg/mL EGCG预处理HaCaT细胞,然后用800U/mL IFN-γ诱导HaCaT细胞,结果发现紫杉叶素和EGCG均可以抑制iNOS蛋白的表达,并且EGCG的效果更好.因此,单体类黄酮紫杉叶素和EGCG可用于皮肤炎症的治疗,并在相同浓度下EGCG效果更强. 展开更多
关键词 紫杉叶素 L-(-)-表没食子儿茶素没食子酸酯 γ-干扰素 人表皮角质细胞HaCaT 诱导型-氧化氮合成酶
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Taxifolin attenuates liver fibrosis by regulating the phosphorylation of NDRG1 at Thr328 via hepatocyte-stellate cell cross talk
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作者 Chuan Ding Zeping Wang +11 位作者 Kao Shi Sunan Li Xinyue Dou Yan Ning Gang Cheng Qiao Yang Xianan Sang Mengyun Peng Qiang Lyu Lu Wang Xin Han Gang Cao 《Acta Pharmaceutica Sinica B》 2025年第4期2059-2076,共18页
Taxifolin(TAX)is a natural compound known for its liver protection effect,but the mechanism remains unknown.Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event... Taxifolin(TAX)is a natural compound known for its liver protection effect,but the mechanism remains unknown.Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis.We established models with NDRG1 knockout(KO)in vivo and in vitro,demonstrating that NDRG1 KO attenuated the development of hepatocyte injury,and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury.Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase,subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site.NDRG1 T328A(phosphorylated mutation)and T328E(mimic phosphorylation)in vivo and in vitro confirmed that pNDRG1T328 exacerbates hepatocyte injury along with DNA damage,inflammatory response,and apoptosis,thereby contributing to hepatic stellate cells(HSCs)activation.In contrast,TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis.Overall,TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1T328 in hepatocytes. 展开更多
关键词 taxifolin Liver fibrosis pNDRG1T328 HEPATOCYTE Liver injury HSCS CROSS-TALK Proteomics
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基于RhoA/ROCK1通路探讨花旗松素对缺氧/复氧诱导的心肌细胞损伤的影响
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作者 徐颖 李丽华 +1 位作者 刘晨 张宁 《河北医学》 2026年第2期240-247,共8页
目的:基于RhoA/ROCK1通路,探讨花旗松素(TAX)对缺氧/复氧(H/R)诱导的心肌细胞损伤的影响。方法:CCK-8筛选TAX处理H/R诱导H9C2的最佳浓度;H9C2细胞分为正常组、H/R组、H/R+TAX组、H/R+ROCK抑制剂(Y-27632)组、H/R+TAX+RhoA激活剂溶血磷脂... 目的:基于RhoA/ROCK1通路,探讨花旗松素(TAX)对缺氧/复氧(H/R)诱导的心肌细胞损伤的影响。方法:CCK-8筛选TAX处理H/R诱导H9C2的最佳浓度;H9C2细胞分为正常组、H/R组、H/R+TAX组、H/R+ROCK抑制剂(Y-27632)组、H/R+TAX+RhoA激活剂溶血磷脂酸(LPA)组。台盼蓝染色检测各组H9C2细胞存活率;试剂盒检测各组H9C2细胞LDH释放率;流式细胞仪和TUENL染色检测各组H9C2细胞凋亡率;DCFH-DA法和ELISA检测各组H9C2细胞氧化应激和炎症反应;Western blot检测各组H9C2细胞RhoA/ROCK1通路相关蛋白表达。结果:与对照组比较,H/R组H9C2细胞存活率明显降低(P<0.05);与H/R组比较,H/R+TAX 20μmoL/L组和H/R+TAX 40μmoL/L组H9C2细胞存活率明显升高(P<0.05);与H/R+TAX 40μmoL/L组比较,H/R+TAX 80μmoL/L组H9C2细胞存活率明显降低(P<0.05)。与对照组比较,H/R组H9C2细胞存活率、GSH-Px下调,LDH释放率、凋亡率以及TUENL阳性细胞数、ROS荧光强度、MDA、NOX4、IL-6、TNF-α、NLRP3、ICAM-1、RhoA、ROCK1、p-MLC2/MLC2上调(P<0.05);与H/R组比较,H/R+TAX组和H/R+Y-27632组H9C2细胞存活率、GSH-Px上调,LDH释放率、凋亡率以及TUENL阳性细胞数、ROS荧光强度、MDA、NOX4、IL-6、TNF-α、NLRP3、ICAM-1、ROCK1、p-MLC2/MLC2下调(P<0.05);与H/R+TAX组比较,H/R+TAX+LPA组H9C2细胞存活率、GSH-Px下调,LDH释放率、凋亡率以及TUENL阳性细胞数、ROS荧光强度、MDA、NOX4、IL-6、TNF-α、NLRP3、ICAM-1、RhoA、ROCK1、p-MLC2/MLC2上调(P<0.05)。结论:TAX通过抑制RhoA/ROCK1通路调控氧化应激、炎症反应和细胞凋亡,缓解H/R诱导的心肌细胞损伤。 展开更多
关键词 花旗松素 缺氧/复氧 心肌细胞 RhoA/ROCK1通路
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Taxifolin attenuates inflammation via suppressing MAPK signal pathway in vitro and in silico analysis
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作者 Xingyan Zhang Xiaoyan Lian +7 位作者 Huling Li Wenjing Zhao Xin Li Fujun Zhou Yutong Zhou Tao Cui Yuli Wang Changxiao Liu 《Chinese Herbal Medicines》 CAS 2022年第4期554-562,F0002,共10页
Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity.... Objective:Taxifolin is a natural flavonoid compound that can be isolated from onions,grapes,oranges and grapefruit.It also acts as a medicine food homology with extraordinary antioxidant and antiinflammatory activity.This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction.Methods:Levels of interleukin(IL)-6,IL-1βand intracellular reactive oxygen species(ROS)were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide(LPS).Subsequently,the m RNA and protein levels of inducible nitric oxide synthase(i NOS),vascular endothelial growth factor(VEGF),cyclooxygenase(COX)-2,tumor necrosis factor(TNF)-a and the phosphorylation expression levels of the MAPK signal pathway were also evaluated.A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway.And then MAPK inhibitors were used to reveal the expression level of i NOS,VEGF,COX-2 and TNF-a in RAW264.7 cells.Results:It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin.Then,the m RNA and protein levels of i NOS,VEGF,COX-2 and TNF-a were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well.In silico analysis,taxifolin could form a relatively stable combination with MAPK signal pathway.MAPK inhibitors showed increasing or decreasing effect in the m RNA levels of i NOS,VEGF,COX-2 and TNF-a,which suggesting that taxifolin down-regulated i NOS,VEGF,COX-2 and TNF-a expressions were not entirely through the MAPK pathway.Conclusion:This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress. 展开更多
关键词 MAPK signal pathway molecular docking pro-inflammatory cytokines taxifolin
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桑黄化学成分、药理活性研究进展及质量标志物(Q-Marker)预测 被引量:1
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作者 赵鹏 李彩霞 +3 位作者 左凡娇 欧阳慧子 毛浩萍 何俊 《药物评价研究》 北大核心 2025年第4期1002-1015,共14页
桑黄是一种应用广泛的药用真菌。现代研究表明桑黄的化学成分主要为多糖、酚酸、黄酮、萜类、甾体等,具有抗炎、抗肿瘤、镇静催眠、降血糖等多种药理作用。基于桑黄化学成分和药理作用的研究进展,从物质功效关联性、有效性、特有性、可... 桑黄是一种应用广泛的药用真菌。现代研究表明桑黄的化学成分主要为多糖、酚酸、黄酮、萜类、甾体等,具有抗炎、抗肿瘤、镇静催眠、降血糖等多种药理作用。基于桑黄化学成分和药理作用的研究进展,从物质功效关联性、有效性、特有性、可测性及传递性,对桑黄质量标志物(Q-Marker)进行推测,预测麦角甾醇、phellibaumin D及包括桑黄素、花旗松素等在内的黄酮类成分可能为桑黄Q-Marker的候选成分。 展开更多
关键词 桑黄 质量标志物 黄酮 酚类 萜类 麦角甾醇 phellibaumin D 桑黄素 花旗松素
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二氢槲皮素抑制α-葡萄糖苷酶的机理研究 被引量:1
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作者 潘俊坤 焦中高 张强 《中国食物与营养》 2025年第10期74-80,共7页
目的:α-葡萄糖苷酶是治疗糖尿病的重要靶点,相关研究表明,二氢槲皮素对α-葡萄糖苷酶具有一定的抑制能力。方法:为进一步探究二氢槲皮素对α-葡萄糖苷酶的抑制作用,本研究考察了不同浓度的二氢槲皮素对α-葡萄糖苷酶的抑制活性,并进一... 目的:α-葡萄糖苷酶是治疗糖尿病的重要靶点,相关研究表明,二氢槲皮素对α-葡萄糖苷酶具有一定的抑制能力。方法:为进一步探究二氢槲皮素对α-葡萄糖苷酶的抑制作用,本研究考察了不同浓度的二氢槲皮素对α-葡萄糖苷酶的抑制活性,并进一步利用酶动力学、荧光光谱、分子对接等实验手段阐明了二氢槲皮素与α-葡萄糖苷酶的互作机制。结果:二氢槲皮素对α-葡萄糖苷酶具有可逆的非竞争性抑制作用,其半数抑制浓度为(35.93±1.56)μg/mL,显著低于阿卡波糖的(471.04±2.67)μg/mL;二氢槲皮素主要通过氢键和范德华力作用与α-葡萄糖苷酶形成基态复合物,造成α-葡萄糖苷酶内在荧光的猝灭;二氢槲皮素结合于α-葡萄糖苷酶分子的一个疏水口袋中,与PHE-157、HIS-239、ASN-241、SER-308、PHE-310残基形成较强的氢键,并与周围残基存在有范德华力、π-π堆积、静电相互作用,共同维持该复合物的结构。结论:本研究对开发防治糖尿病的功能性食品具有一定的参考意义。 展开更多
关键词 二氢槲皮素 Α-葡萄糖苷酶 抑制 互作 分子对接
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花旗松素通过PPARα对棕榈酸钠诱导的HepG2细胞脂代谢的调节作用
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作者 陈富春 徐奔 +3 位作者 沈维军 刘磊 万发春 程安玮 《食品与发酵工业》 北大核心 2025年第24期86-94,共9页
为探究花旗松素(taxifolin,TAX)对棕榈酸钠(ammonium palmitate,PA)诱导的HepG细胞脂代谢的影响及其调节作用机制。该文通过CCK8法筛选合适的建模浓度以及TAX安全添加浓度,用油红O染色进一步验证构建模型。同时测定甘油三酯(triglycerid... 为探究花旗松素(taxifolin,TAX)对棕榈酸钠(ammonium palmitate,PA)诱导的HepG细胞脂代谢的影响及其调节作用机制。该文通过CCK8法筛选合适的建模浓度以及TAX安全添加浓度,用油红O染色进一步验证构建模型。同时测定甘油三酯(triglyceride,TG)以及活性氧(reactive oxygen species,ROS)的含量,利用实时荧光定量PCR(real-time quantitative reverse transcription PCR,RT-qPCR)技术检测A羧化酶(acetyl-CoA carboxylase,ACC)、硬脂酰辅酶A去饱和酶(stearoyl-CoA desaturase,SCD)、CCAAT增强子结合蛋白α(CCAAT enhancer binding proteinα,C/EBP-α)、甾醇调节元件结合蛋白1C(sterol regulatory element binding protein 1C,SREBP-1C)、氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptorα,PPARα)的基因表达。利用蛋白免疫印迹(Western blot,WB)测定脂肪酸合酶(fatty acid synthase,FAS)、白细胞分化抗原36(cluster of differentiation 36,CD36)、腺苷酸活化蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)以及PPARα的蛋白表达,并用免疫荧光测定FAS以及PPARα的蛋白表达水平。使用小干扰RNA(small interfering RNA,si RNA)对PPARα进行沉默处理,进一步验证TAX对脂代谢的调控机制。结果150μmol/L的TAX降低了PA处理HepG2细胞中TG的水平(P<0.01),各个浓度的TAX处理均使得ROS的含量显著下降(P<0.01)。150μmol/L浓度时显著下调了ACC、SCD、C/EBP-α、SREBP-1C的表达,上调了PPARα的mRNA表达(P<0.01)。所有浓度均可以显著上调PPARα的蛋白表达以及AMPK的磷酸化水平(P<0.05),显著下调FAS以及CD36的蛋白表达(P<0.01)。所有浓度的TAX均能显著上调PPARα,下调FAS的免疫荧光强度(P<0.01)。si RNA PPARα抑制了TAX的保护作用。上述结果表明,TAX能够介导PPARα信号通路调节脂质积累,改善PA引起的HepG2细胞脂代谢紊乱。 展开更多
关键词 花旗松素 脂代谢 信号通路 基因沉默 HEPG2细胞
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花旗松素-磷脂/胆盐/聚维酮-K30胶束的构建及对酒精性肝损伤的保护作用
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作者 张诗雨 孙敬蒙 +3 位作者 李冬冬 张欣 张佳慧 张炜煜 《药学学报》 北大核心 2025年第2期488-497,共10页
花旗松素(taxifolin,Tax)已被证实可作为药食同源的可食用物质,具有保护酒精性肝损伤作用,然而其亲水性和渗透性均较差,阻碍了Tax的临床应用。本研究制备了花旗松素-磷脂/胆盐/聚维酮-K30(taxifolinphosphatidylcholine/sodium deoxycho... 花旗松素(taxifolin,Tax)已被证实可作为药食同源的可食用物质,具有保护酒精性肝损伤作用,然而其亲水性和渗透性均较差,阻碍了Tax的临床应用。本研究制备了花旗松素-磷脂/胆盐/聚维酮-K30(taxifolinphosphatidylcholine/sodium deoxycholate/PVP-K30 micells,Tax-MLs)纳米胶束,采用Box-Behnken试验得到最佳制备工艺,以透射电镜、傅里叶红外光谱等对Tax-MLs进行表征;测定临界胶束浓度、平衡溶解度及油水分配系数等理化参数,并通过体外消化模拟试验探讨Tax-MLs的释放规律;酒精性肝损伤模型探讨Tax-MLs的体内药效。结果显示,Tax-MLs的平均粒径、多分散性指数及zeta电位分别为36.90±4.57 nm、0.194±0.01及-32.6±0.35 mV,透射电镜观测到Tax-MLs呈现大小均一,分布均匀的类球形,差式扫描量热分析和傅里叶红外光谱等证明Tax-MLs的形成;理化性质方面,Tax-MLs相较Tax在水中的溶解度提高了92.02倍,其在水中的油水分配系数也从0.43增加到1.14,证明Tax-MLs能够提高其溶解度及渗透性;体内药效学结果显示,与Tax组相比,Tax-MLs低、中、高剂量组肝脏指数及血清中谷草转氨酶和谷丙转氨酶水平显著降低(P<0.05),增强肝组织中超氧化物歧化酶、谷胱甘肽活性,降低丙二醛水平的效果更明显。Tax-MLs有效提高了药物的溶解度和渗透性,并增强了对酒精性肝损伤的保护作用。本研究体内动物实验得到了长春中医药大学动物伦理委员会的批准(批准号:2023601)。 展开更多
关键词 花旗松素 纳米胶束 制备工艺 酒精性肝损伤 表征
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花旗松素调节Shh/Gli1信号通路对骨关节炎大鼠软骨损伤的影响
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作者 钱文旭 杨成天 +1 位作者 谢文娟 杨蓉 《中国免疫学杂志》 北大核心 2025年第11期2619-2623,2630,共6页
目的:探讨花旗松素调节音猬因子(Shh)/Gli家族锌指蛋白1(Gli1)信号通路对骨关节炎(OA)大鼠软骨损伤的影响。方法:大鼠随机分为对照组、OA组、花旗松素组、Shh激活剂(嘌吗啡胺)组、花旗松素+嘌吗啡胺组,每组12只。除对照组外,其他各组大... 目的:探讨花旗松素调节音猬因子(Shh)/Gli家族锌指蛋白1(Gli1)信号通路对骨关节炎(OA)大鼠软骨损伤的影响。方法:大鼠随机分为对照组、OA组、花旗松素组、Shh激活剂(嘌吗啡胺)组、花旗松素+嘌吗啡胺组,每组12只。除对照组外,其他各组大鼠均通过改良Hulth法构建OA模型,建模成功后开始给药处理,给药1次/d,持续4周。检测大鼠膝关节肿胀度及最大活动度的变化;番红O-固绿染色检测大鼠膝关节软骨组织病理变化,并进行国际骨关节炎研究会(OARSI)评分;ELISA检测膝关节软骨组织中IL-1β、TNF-α、IL-10水平;免疫组化染色检测膝关节软骨组织中ADAMTS-5、MMP-13表达;Western blot检测膝关节软骨组织中Shh、Gli1蛋白表达。结果:与对照组相比,OA组大鼠软骨表面破坏,软骨侵蚀,细胞明显减少,膝关节肿胀度、OARSI评分、膝关节软骨组织中IL-1β、TNF-α水平、ADAMTS-5、MMP-13阳性细胞百分数及Shh、Gli1蛋白表达升高,最大活动度、膝关节软骨组织中IL-10水平降低(P<0.05);与OA组相比,花旗松素组大鼠软骨表面破坏、软骨侵蚀及细胞减少现象有所缓解,膝关节肿胀度、OARSI评分、膝关节软骨组织中IL-1β、TNF-α水平、ADAMTS-5、MMP-13阳性细胞百分数及Shh、Gli1蛋白表达降低,最大活动度、膝关节软骨组织中IL-10水平升高,嘌吗啡胺组对应指标变化趋势与花旗松素组相反(P<0.05);与花旗松素组相比,花旗松素+嘌吗啡胺组大鼠膝关节软骨组织病理损伤加剧,膝关节肿胀度、OARSI评分、膝关节软骨组织中IL-1β、TNF-α水平、ADAMTS-5、MMP-13阳性细胞百分数及Shh、Gli1蛋白表达升高,最大活动度、膝关节软骨组织中IL-10水平降低(P<0.05)。结论:花旗松素对OA大鼠软骨损伤的改善机制可能与抑制Shh/Gli1信号通路有关。 展开更多
关键词 花旗松素 音猬因子/Gli家族锌指蛋白1信号通路 骨关节炎 炎症 基质降解
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基于USP18探讨花旗松素对放射性肺损伤保护作用的实验研究
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作者 陈佳佳 于然 +4 位作者 李庆菊 陈皓瑜 宋坚 郁汉旭 王万鹏 《现代肿瘤医学》 2025年第11期1846-1853,共8页
目的:探讨花旗松素(Taxifolin,TAX)对X射线致放射性肺损伤的保护作用及机制。方法:将20只C57BL/6小鼠按随机数表法分为对照组、模型组、给药组、治疗组,每组5只。给药组、治疗组辐照前3天给予花旗松素腹腔注射(30 mg/kg),模型组、治疗... 目的:探讨花旗松素(Taxifolin,TAX)对X射线致放射性肺损伤的保护作用及机制。方法:将20只C57BL/6小鼠按随机数表法分为对照组、模型组、给药组、治疗组,每组5只。给药组、治疗组辐照前3天给予花旗松素腹腔注射(30 mg/kg),模型组、治疗组给予6 MV X射线,15 Gy单次全胸腔照射,构建放射性肺损伤小鼠模型,辐照后治疗组采取每隔1天给药,连续给药至6周,24周后处死小鼠并取材。HE染色检测肺组织病理形态;马松染色检测肺组织纤维化;细胞衰老β-半乳糖苷酶(SA-β-Gal)染色检测肺组织细胞衰老情况;免疫组化检测肺组织去泛素化酶(USP18)、Yes相关蛋白(YAP)表达;Western blot检测核因子p21、p16、USP18蛋白表达。结果:与模型组相比,治疗组肺组织HE病理评分减小;马松染色(Masson)评分减少;肺组织SA-β-Gal活性降低,且肺组织p21、p16表达减少。与对照组相比,模型组肺组织USP18表达上调,同时YAP表达也增强,二者呈正相关,而治疗组的USP18及YAP表达均减弱。结论:花旗松素可能通过减少USP18抑制细胞衰老发挥对X射线致放射性肺损伤的保护作用,其保护机制可能与调控Hippo通路关键分子YAP,逆转辐照所致的细胞衰老有关。 展开更多
关键词 花旗松素 放射性肺损伤 细胞衰老 去泛素化酶 USP18 YAP
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基于UPLC特征图谱和2种成分含量测定的皂角刺药材质量评价
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作者 位翠杰 刘晓霞 +8 位作者 冯涌微 张芳平 段志文 谢文凯 夏天睿 李振雨 何民友 陈向东 孙冬梅 《药学前沿》 2025年第2期227-235,共9页
目的建立皂角刺药材超高效液相色谱(UPLC)特征图谱及测定东莨菪内酯、花旗松素含量的方法,为全面评价皂角刺药材的质量提供参考。方法采用UPLC法建立了皂角刺药材特征图谱并同时测定东莨菪内酯、花旗松素2种有效成分含量的方法。根据特... 目的建立皂角刺药材超高效液相色谱(UPLC)特征图谱及测定东莨菪内酯、花旗松素含量的方法,为全面评价皂角刺药材的质量提供参考。方法采用UPLC法建立了皂角刺药材特征图谱并同时测定东莨菪内酯、花旗松素2种有效成分含量的方法。根据特征图谱和含量测定结果,对17批皂角刺药材进行聚类分析,并对不同产地药材和常见伪品进行对比分析。结果建立皂角刺药材特征图谱,确定8个特征峰,经质谱分析及与对照品比对,确认其中6个特征峰的成分,分别为原儿茶醛、东莨菪苷、东莨菪内酯、花旗松素、牡荆素和异牡荆素;17批皂角刺药材被为两类;河南省洛阳市产地药材含量较高,陕西省和四川省产地药材中花旗松素含量较低;所建立特征图谱和含量测定方法均能对其常见的4种伪品进行快速、有效地区分鉴别。结论该方法为建立完善的皂角刺药材质量标准及全面评价其质量提供参考。 展开更多
关键词 皂角刺 超高效液相色谱特征图谱 东莨菪内酯 花旗松素 伪品
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一测多评法同时测定皂角刺中12种成分的含量
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作者 刘小燕 宋平顺 +2 位作者 张明童 马潇 张义福 《现代中药研究与实践》 2025年第1期49-54,共6页
目的建立一测多评法同时测定皂角刺中原儿茶酸、对羟基苯甲酸、香草酸、丁香酸、表儿茶素、异荭草苷、牡荆苷、异牡荆苷、花旗松素、槲皮苷、木犀草素、槲皮素的含量。方法采用SEVATM C18 Opal(250 mm×4.6 mm,5μm)色谱柱;乙腈-0.1... 目的建立一测多评法同时测定皂角刺中原儿茶酸、对羟基苯甲酸、香草酸、丁香酸、表儿茶素、异荭草苷、牡荆苷、异牡荆苷、花旗松素、槲皮苷、木犀草素、槲皮素的含量。方法采用SEVATM C18 Opal(250 mm×4.6 mm,5μm)色谱柱;乙腈-0.1%甲酸溶液为流动相,梯度洗脱;流速为0.6 mL/min;柱温为32℃;检测波长为260 nm、230 nm。以花旗松素为内参物,计算其它11种成分的相对校正因子,采用一测多评法与外标法分别测定皂角刺中12种成分的含量,并对测定结果进行比较。结果原儿茶酸、对羟基苯甲酸、香草酸、丁香酸、表儿茶素、异荭草苷、牡荆苷、异牡荆苷、槲皮苷、木犀草素、槲皮素的相对校正因子分别为1.104、0.777、1.166、2.084、1.378、1.670、2.269、1.803、1.399、1.258、1.142。一测多评法与外标法测得含量值无显著性差异(P>0.05)。结论所建立的一测多评法结果准确、可行性高,可用于皂角刺的质量控制。 展开更多
关键词 皂角刺 一测多评 相对校正因子 花旗松素
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花旗松素调节环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子信号通路对结直肠癌细胞增殖、凋亡及免疫逃逸的影响
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作者 高阳 陈小华 翟蕾 《河北中医》 2025年第10期1673-1677,1683,共6页
目的研究探讨花旗松素(TAX)调节环磷酸鸟苷-腺苷酸合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对结直肠癌(CRC)细胞增殖、凋亡及免疫逃逸的影响。方法首先使用不同浓度的TAX(2.5、5.0、10.0、20.0、40.0、80.0μmol/L)处理CRC细胞(... 目的研究探讨花旗松素(TAX)调节环磷酸鸟苷-腺苷酸合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对结直肠癌(CRC)细胞增殖、凋亡及免疫逃逸的影响。方法首先使用不同浓度的TAX(2.5、5.0、10.0、20.0、40.0、80.0μmol/L)处理CRC细胞(HCT116),进行浓度筛选。然后将HCT116细胞进行分组,分别为对照组(Control组)、TAX低浓度组(TAX-L)、TAX中浓度组(TAX-M)、TAX高浓度组(TAX-H)、TAX高浓度+cGAS抑制剂组(TAX-H+RU.521组)。最后采用CCK-8法与平板克隆形成实验检测细胞增殖,用流式细胞仪检测细胞凋亡,蛋白免疫印迹法(Western blot)检测通路蛋白(cGAS、STING)表达,将自然杀伤细胞(NK)与HCT116细胞共培养24 h,检测NK细胞对HCT116细胞的杀伤率,用酶联免疫吸附法(ELISA)检测细胞上清液中肿瘤坏死因子β(TNF-β)、白细胞介素8(IL-8)、IL-10水平。结果经筛选最后选择TAX浓度为10.0、20.0、40.0μmol/L进行后续实验。与Control组比较,TAX-L组、TAX-M组、TAX-H组细胞集落形成数依次降低(P<0.05),细胞凋亡率及cGAS、STING蛋白表达依次升高(P<0.05);与TAX-H组相比,TAX-H+RU.521组细胞集落形成数升高,细胞凋亡率降低、cGAS、STING表达下调(P<0.05)。NK细胞与HCT116细胞共培养后,与Control组相比,TAX-L组、TAX-M组、TAX-H组NK细胞杀伤率依次升高(P<0.05),TNF-β、IL-8、IL-10水平依次降低(P<0.05);与TAX-H组比较,TAX-H+RU.521组NK细胞杀伤率降低,TNF-β、IL-8、IL-10水平升高(P<0.05)。结论TAX可以通过激活cGAS-STING信号通路抑制CRC细胞增殖、凋亡及免疫逃逸。 展开更多
关键词 结直肠癌 花旗松素 环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子信号通路 实验研究
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花旗松素对人宫颈癌Hela细胞的体外抗肿瘤活性及其机理研究 被引量:28
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作者 翟延君 程飞 +2 位作者 王添敏 初正云 李娜 《中成药》 CAS CSCD 北大核心 2011年第12期2052-2055,共4页
目的观察和探索花旗松素对人宫颈癌Hela细胞的体外抗肿瘤活性及其作用机理。方法结晶紫染色法检测花旗松素对人宫颈癌Hela细胞的增殖抑制作用;RT-PCR法检测与肿瘤细胞凋亡相关基因的表达。结果花旗松素能够抑制人宫颈癌Hela细胞的增殖,... 目的观察和探索花旗松素对人宫颈癌Hela细胞的体外抗肿瘤活性及其作用机理。方法结晶紫染色法检测花旗松素对人宫颈癌Hela细胞的增殖抑制作用;RT-PCR法检测与肿瘤细胞凋亡相关基因的表达。结果花旗松素能够抑制人宫颈癌Hela细胞的增殖,呈剂量依赖关系;花旗松素不能诱导Bcl-2 mRNA和Bax mRNA的表达,但能使P53和P21的mRNA表达量增加。结论花旗松素具有良好的体外抑制人宫颈癌Hela细胞增殖作用;花旗松素诱导Hela细胞死亡与细胞凋亡相关,其分子机制可能与升高P53和P21mRNA表达有关,而与Bcl-2和Bax的蛋白转录无关。 展开更多
关键词 花旗松素 人宫颈癌HELA细胞 抗肿瘤作用 RT-PCR
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