A series of monosubstituted troxerutin esters have been synthesized by enzyme-catalyzed regioselective acylation of troxerutin in nonaqueous medium.Using divinyl dicarboxylates(CH_2=CH-OOC-(CH_2)_n-COO-CH=CH_2,n = 2,3...A series of monosubstituted troxerutin esters have been synthesized by enzyme-catalyzed regioselective acylation of troxerutin in nonaqueous medium.Using divinyl dicarboxylates(CH_2=CH-OOC-(CH_2)_n-COO-CH=CH_2,n = 2,3,4,7,8,11) featuring different chain length as acyl donors and alkaline protease from Bacillus subtilis as catalyst,troxerutin was regioselective acylated at B ethoxyl group.The results indicated that the regioselectivity of the enzyme-catalyzed acylation was not affected by the chain length o...展开更多
Troxerutin fatty acid esters were prepared using troxerutin and fatty acid vinyl esters as substrates in pyridine through enzymatic route. The structures of as-prepared compounds were identified by FT-TR, NMR, and ESI...Troxerutin fatty acid esters were prepared using troxerutin and fatty acid vinyl esters as substrates in pyridine through enzymatic route. The structures of as-prepared compounds were identified by FT-TR, NMR, and ESI-HRMS. Using alkaline protease(≥30 mg/mL) as enzyme, maximum yields reached 58% at 3:1(vinyl hexanoate to troxerutin) in pyridine(water content ≤1%). The yields gradually declined as chain length of acyl donors rose. The antioxidation abilities of the as-obtained compounds were confirmed by both DPPH free radical scavenging and potassium ferricyanide reduction methods. The antioxidation ability of troxerutin fatty acid esters was found lower than that of troxerutin. However, the logP values of troxerutin fatty acid esters varied from 0.15 to 1.94, suggesting that troxerutin fatty acid esters had better lipophilicity than troxerutin(logP =-2.12) when compared to their oil-water distribution coefficients. Overall, these findings look promising as reference for further development of future troxerutin.展开更多
[Objectives]This study aims to establish a simple,convenient,fast,low-cost,low-consumption and efficient method for quality control of troxerutin.[Methods]In NaAc-phosphate buffer at pH=8,troxerutin could react with C...[Objectives]This study aims to establish a simple,convenient,fast,low-cost,low-consumption and efficient method for quality control of troxerutin.[Methods]In NaAc-phosphate buffer at pH=8,troxerutin could react with Cu^2+to form complex,which had a characteristic absorption peak at 408 nm in the ultraviolet spectrum.The content of troxerutin could be determined indirectly by measuring the absorbance of the complex.[Results]Within the linear range of 27.82-74.19μg/mL,the absorbance of the complex has a good linear relationship with the concentration of troxerutin.The regression equation is A=0.0119C-0.1384(r=0.9991),and the detection limit is 1.59μg/mL.This method used to determine the content of troxerutin in samples from different manufacturers,and the recovery is 100.9%-102.7%.[Conclusions]The ultraviolet spectrophotometry is used in this experiment to indirectly determine the content of troxerutin by measuring the absorbance of troxerutin-Cu^2+complex,and the results are accurate,reproducible and highly precise.This method can be used for quantitative analysis of troxerutin.展开更多
Troxerutin(TRO)is a mixture of semi-synthetic flavonoids prepared by hydroxyethylation of rutin,and it is commonly used for the treatment of cerebrovascular diseases.The main active ingredient is trishydroxyethyl ruti...Troxerutin(TRO)is a mixture of semi-synthetic flavonoids prepared by hydroxyethylation of rutin,and it is commonly used for the treatment of cerebrovascular diseases.The main active ingredient is trishydroxyethyl rutin.The mother liquor of TRO contains a lot of TRO and other derivatives of hydroxyethylated rutin.In order to make full use of the mother liquor of TRO,an efficient method was developed for recovering high-purity TRO from mother liquor of TRO by combining silica gel column chromatography with semi-preparative liquid chromatography.In the silica gel column chromatographic separation,the ratio of silica gel to sample and eluent composition were investigated to obtain optimum separation effect.The results showed that when the ratio of silica gel to sample was 50,and acetone–ethyl acetate–water–glacial acetic acid(10:10:3:1,v/v/v/v)was used as the eluent,the separation effect of TRO and adjacent impurities was good.Moreover,150 g of TRO with a purity of 80%could be obtained from 1 kg of mother liquor of TRO by the silica gel column chromatographic separation,and the results were consistent with the quality standard of TRO raw material.Subsequently,the semi-preparative HPLC was performed,and 100 g TRO with a purity of up to 98%(w/w)was obtained.Meanwhile,tetrahydroxyethylrutin and tetrahydroxyethylquercetin with purity greater than 98%were obtained.This work proposed the separation and preparation of TRO with high-purity from the production waste of TRO for the first time,which had certain environmental benefits and economic benefits.展开更多
目的:铁死亡被证实在结直肠癌发生、发展和治疗中发挥重要作用。曲克芦丁具有多种生物学活性,但其是否与铁死亡有关还不得而知。本研究旨在探讨曲克芦丁对人正常结肠上皮细胞和结直肠癌细胞铁死亡的影响。方法:采用噻唑蓝(methylthiazol...目的:铁死亡被证实在结直肠癌发生、发展和治疗中发挥重要作用。曲克芦丁具有多种生物学活性,但其是否与铁死亡有关还不得而知。本研究旨在探讨曲克芦丁对人正常结肠上皮细胞和结直肠癌细胞铁死亡的影响。方法:采用噻唑蓝(methylthiazolyldiphenyl-tetrazolium bromide,MTT)法检测曲克芦丁对铁死亡诱导剂Erastin诱导的结肠上皮细胞及结直肠癌细胞的细胞活力的影响,流式细胞仪检测曲克芦丁对细胞内脂质过氧化物、亚铁离子水平的影响,比色法检测细胞内丙二醛(malondialdehyde,MDA)及还原型谷胱甘肽(reduced glutathione,GSH)/氧化型谷胱甘肽(oxidized glutathione disulfide,GSSG)比值的变化,荧光染色法检测细胞线粒体膜电位。使用网络药理学和分子对接技术预测曲克芦丁参与铁死亡的潜在靶点,并采用蛋白质印迹法对其潜在靶点进行验证。结果:曲克芦丁能有效逆转由Erastin诱导的结肠上皮细胞和结直肠癌细胞铁死亡,并能显著降低由Erastin引起的细胞内脂质过氧化物、亚铁离子和MDA水平升高,提高细胞内GSH/GSSG比值、线粒体膜电位及胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)和谷胱甘肽过氧化酶4(glutathione peroxidase 4,GPX4)的表达水平;网络药理学、分子对接及蛋白质印迹法检测结果显示肿瘤蛋白p53(tumor protein p53,TP53)可能是曲克芦丁抑制结肠上皮细胞及结直肠癌细胞铁死亡的潜在靶点。结论:曲克芦丁通过降低TP53水平来抑制结肠上皮细胞和结直肠癌细胞的铁死亡。展开更多
基金the Science and Technology hall of Henan Province(No.072300420070No.82102330014)China,for financially supported to this work.
文摘A series of monosubstituted troxerutin esters have been synthesized by enzyme-catalyzed regioselective acylation of troxerutin in nonaqueous medium.Using divinyl dicarboxylates(CH_2=CH-OOC-(CH_2)_n-COO-CH=CH_2,n = 2,3,4,7,8,11) featuring different chain length as acyl donors and alkaline protease from Bacillus subtilis as catalyst,troxerutin was regioselective acylated at B ethoxyl group.The results indicated that the regioselectivity of the enzyme-catalyzed acylation was not affected by the chain length o...
基金financially supported by Science and Technology Department of Henan Province (No. 132102310028)the Program for Innovative Research Team from Zhengzhou (No. 131PCXTD605)
文摘Troxerutin fatty acid esters were prepared using troxerutin and fatty acid vinyl esters as substrates in pyridine through enzymatic route. The structures of as-prepared compounds were identified by FT-TR, NMR, and ESI-HRMS. Using alkaline protease(≥30 mg/mL) as enzyme, maximum yields reached 58% at 3:1(vinyl hexanoate to troxerutin) in pyridine(water content ≤1%). The yields gradually declined as chain length of acyl donors rose. The antioxidation abilities of the as-obtained compounds were confirmed by both DPPH free radical scavenging and potassium ferricyanide reduction methods. The antioxidation ability of troxerutin fatty acid esters was found lower than that of troxerutin. However, the logP values of troxerutin fatty acid esters varied from 0.15 to 1.94, suggesting that troxerutin fatty acid esters had better lipophilicity than troxerutin(logP =-2.12) when compared to their oil-water distribution coefficients. Overall, these findings look promising as reference for further development of future troxerutin.
基金Basic Ability Enhancement Project for Young and Middle-aged Teachers in Colleges and Universities of Guangxi in 2017(2017KY0284)Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine(GXZYKF2019-7)Collaborative Innovation Center of Zhuang and Yao Ethnic Medicine[(2013)No.20].
文摘[Objectives]This study aims to establish a simple,convenient,fast,low-cost,low-consumption and efficient method for quality control of troxerutin.[Methods]In NaAc-phosphate buffer at pH=8,troxerutin could react with Cu^2+to form complex,which had a characteristic absorption peak at 408 nm in the ultraviolet spectrum.The content of troxerutin could be determined indirectly by measuring the absorbance of the complex.[Results]Within the linear range of 27.82-74.19μg/mL,the absorbance of the complex has a good linear relationship with the concentration of troxerutin.The regression equation is A=0.0119C-0.1384(r=0.9991),and the detection limit is 1.59μg/mL.This method used to determine the content of troxerutin in samples from different manufacturers,and the recovery is 100.9%-102.7%.[Conclusions]The ultraviolet spectrophotometry is used in this experiment to indirectly determine the content of troxerutin by measuring the absorbance of troxerutin-Cu^2+complex,and the results are accurate,reproducible and highly precise.This method can be used for quantitative analysis of troxerutin.
基金Shaanxi science and technology hall project(Grant No.2018JM7060)Provincial Key Discipline Construction Project of pharmacy of Xi’an Medical University(Grant No.2016YXXK08)。
文摘Troxerutin(TRO)is a mixture of semi-synthetic flavonoids prepared by hydroxyethylation of rutin,and it is commonly used for the treatment of cerebrovascular diseases.The main active ingredient is trishydroxyethyl rutin.The mother liquor of TRO contains a lot of TRO and other derivatives of hydroxyethylated rutin.In order to make full use of the mother liquor of TRO,an efficient method was developed for recovering high-purity TRO from mother liquor of TRO by combining silica gel column chromatography with semi-preparative liquid chromatography.In the silica gel column chromatographic separation,the ratio of silica gel to sample and eluent composition were investigated to obtain optimum separation effect.The results showed that when the ratio of silica gel to sample was 50,and acetone–ethyl acetate–water–glacial acetic acid(10:10:3:1,v/v/v/v)was used as the eluent,the separation effect of TRO and adjacent impurities was good.Moreover,150 g of TRO with a purity of 80%could be obtained from 1 kg of mother liquor of TRO by the silica gel column chromatographic separation,and the results were consistent with the quality standard of TRO raw material.Subsequently,the semi-preparative HPLC was performed,and 100 g TRO with a purity of up to 98%(w/w)was obtained.Meanwhile,tetrahydroxyethylrutin and tetrahydroxyethylquercetin with purity greater than 98%were obtained.This work proposed the separation and preparation of TRO with high-purity from the production waste of TRO for the first time,which had certain environmental benefits and economic benefits.
文摘目的:铁死亡被证实在结直肠癌发生、发展和治疗中发挥重要作用。曲克芦丁具有多种生物学活性,但其是否与铁死亡有关还不得而知。本研究旨在探讨曲克芦丁对人正常结肠上皮细胞和结直肠癌细胞铁死亡的影响。方法:采用噻唑蓝(methylthiazolyldiphenyl-tetrazolium bromide,MTT)法检测曲克芦丁对铁死亡诱导剂Erastin诱导的结肠上皮细胞及结直肠癌细胞的细胞活力的影响,流式细胞仪检测曲克芦丁对细胞内脂质过氧化物、亚铁离子水平的影响,比色法检测细胞内丙二醛(malondialdehyde,MDA)及还原型谷胱甘肽(reduced glutathione,GSH)/氧化型谷胱甘肽(oxidized glutathione disulfide,GSSG)比值的变化,荧光染色法检测细胞线粒体膜电位。使用网络药理学和分子对接技术预测曲克芦丁参与铁死亡的潜在靶点,并采用蛋白质印迹法对其潜在靶点进行验证。结果:曲克芦丁能有效逆转由Erastin诱导的结肠上皮细胞和结直肠癌细胞铁死亡,并能显著降低由Erastin引起的细胞内脂质过氧化物、亚铁离子和MDA水平升高,提高细胞内GSH/GSSG比值、线粒体膜电位及胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)和谷胱甘肽过氧化酶4(glutathione peroxidase 4,GPX4)的表达水平;网络药理学、分子对接及蛋白质印迹法检测结果显示肿瘤蛋白p53(tumor protein p53,TP53)可能是曲克芦丁抑制结肠上皮细胞及结直肠癌细胞铁死亡的潜在靶点。结论:曲克芦丁通过降低TP53水平来抑制结肠上皮细胞和结直肠癌细胞的铁死亡。
