天然中药配合物的抗肿瘤活性及其机制研究
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摘要
近年来抗肿瘤药物发展迅速,种类繁多,但大都不良反应大。天然中药由于不良反应小,故在合成抗肿瘤药物上有很大优势。在中医药领域,中药单体和金属离子的配合物是近年来药物和化学研究的热点和重点。中药配位化学学说强调,中药单体与金属离子形成配合物后可以改变或增强中药单体的活性,并发挥重要的药理作用。了解常见天然中药单体与金属离子配合物的制备、组成和表征,研究天然中药配合物的生物活性以及抗肿瘤作用机制,可为肿瘤的治疗提供新的途径。
In recent years,antitumor drugs have developed rapidly,but mostly have serious adverse effects. Natural Chinese medicine has a great advantage in synthetic anti-tumor drugs because of its small adverse reaction. In the field of traditional Chinese medicine( TCM),the complexes of TCM monomer and metal ion have been the hot spots and focus of drug and chemical research in recent years. The coordination chemistry of TCM theory which emphasizes in the formation of complexes between TCM monomers and metal ions can change or enhance the activity of the TCM monomers and plays an important pharmacological role. Therefore,understanding the preparation,composition and characterization of several common natural Chinese medicines complexes,and further studies of the biological activities and anti-tumor mechanisms will provide a new way for the treatment of tumors.
In recent years,antitumor drugs have developed rapidly,but mostly have serious adverse effects. Natural Chinese medicine has a great advantage in synthetic anti-tumor drugs because of its small adverse reaction. In the field of traditional Chinese medicine( TCM),the complexes of TCM monomer and metal ion have been the hot spots and focus of drug and chemical research in recent years. The coordination chemistry of TCM theory which emphasizes in the formation of complexes between TCM monomers and metal ions can change or enhance the activity of the TCM monomers and plays an important pharmacological role. Therefore,understanding the preparation,composition and characterization of several common natural Chinese medicines complexes,and further studies of the biological activities and anti-tumor mechanisms will provide a new way for the treatment of tumors.
引文
[1]曹治权.中药药效的物质基础和作用机理研究新思路(一)---中药中化学物种形态和生物活性关系的研究[J].上海中医药大学学报,2000,14(1):36-40.
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[15]Sun YJ,Huang QQ,Li P,et al.Catalytic dioxygenation of flavonol by M(Ⅱ)-complexes(M=Mn,Fe,Co,Ni,Cu and Zn)-mimicking the M(Ⅱ)-substituted quercetin 2,3-dioxygenase[J].Dalton Trans,2015,44(31):13926-13238.
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[19]Tan J,Wang B,Zhu L.DNA binding,cytotoxicity,apoptotic inducing activity,and molecular modeling study of quercetin zinc(Ⅱ)complex[J].Bioorg Med Chem,2009,17(2):614-620.
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[21]Li C,Huang Q,Xiao J,et al.Preparation of prunella vulgaris polysaccharide-zinc complex and its antiproliferative activity in Hep G2cells[J].Int J Biol Macromol,2016,91:671-679.
[22]张茜,芮瑞,李佩佩,等.草乌多糖金属配合物的制备、表征与抗癌活性研究[J].郑州大学学报(工学版),2016,37(3):36-39.
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[25]Islas MS,Naso LG,Lezama L.Insights into the mechanisms underlying the antitumor activity of an oxidovanadium(Ⅳ)compound with the antioxidant naringenin.Albumin binding studies[J].J Inorg Biochem,2015,149:12-24.
[26]Ji Y,Dou YN,Zhao QW,et al.Paeoniflorin suppresses TGF-βmediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway[J].Acta Pharmacol Sin,2016,37(6):794-804.
[27]夏小健,黄蓓.芍药苷在治疗肝癌中作用及其机制的研究进展[J].中南药学,2018,16(2):209-212.
[28]晏雪生,李瀚旻,彭亚琴,等.芍药苷对人肝癌细胞Hep G2凋亡及其调控基因的影响[J].中华中医药学刊,2007,25(7):1346-1347.
[29]Lee SM,Li ML,Tse YC,et al.Paeoniae radix,a Chinese herbal extract,inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway[J].Life Sci,2002,71(19):2267-2277.
[30]Hung JY,Yang CJ,Tsai YM,et al.Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligandmediated apoptotic pathway in human non-small cell lung cancer A549 cells[J].Clin Exp Pharmacol Physiol,2008,35(2):141-147.
[31]Hu S,Chen SM,Li XK,et al.Antitumor effects of chi-shen extract from Salvia miltiorrhiza and Paeoniae radix on human hepatocellular carcinoma cells[J].Acta Pharmacol Sin,2007,28(8):1215-1223.
[32]Li W,Qi Z,Wei Z,et al.Paeoniflorin inhibits proliferation and induces apoptosis of human glioma cells via microRNA-16 upregulation and matrix metalloproteinase-9 downregulation[J].Mol Med Rep,2015,12(2):2735-2740.
[33]Shi L,Teng H,Zhu M,et al.Paeoniflorin inhibits nucleus pulposus cell apoptosis by regulating the expression of Bcl-2 family proteins and caspase-9 in a rabbit model of intervertebral disc degeneration[J].Exp Ther Med,2015,10(1):257-262.
[34]Hu PF,Chen WP,Bao JP,et al.Paeoniflorin inhibits IL-1β-induced chondrocyte apoptosis by regulating the Bax/Bcl-2/caspase-3 signaling pathway[J].Mol Med Rep,2018,17(4):6194-6620.
[2]曹治权.中药药效的物质基础和作用机理研究新思路(二)---中药中化学物种形态和生物活性关系的研究[J].上海中医药大学学报,2000,14(2):55-57.
[3]Allardyce CS,Dyson PJ.Metal-based drugs that break the rules[J].Dalton Trans,2016,45(8):3201-3209.
[4]zenver N,Saeed M,Demirezer L,et al.Aloe-emodin as drug candidate for cancer therapy[J].Oncotarget,2018,9(25):17770-17796.
[5]Thimmegowda NR,Park C,Shwetha B,et al.Synthesis and antitumor activity of natural compound aloe emodin derivatives[J].Chem Biol Drug Des,2015,85(5):638-644.
[6]Yang L,Tan J,Wang BCW,et al.Synthesis,characterization,and anti-cancer activity of emodin-Mn(Ⅱ)metal complex[J].Chin JNat Medicines,2014,12(12):937-942.
[7]潘晓丽,向晖,谢运飞,等.大黄素-铜(Ⅱ)配合物的合成、表征及抗氧化活性研究[J].时珍国医国药,2013,24(12):2892-2894.
[8]向晖,潘晓丽,熊永爱,等.大黄酸金属配合物的结构及对人肝癌HepG2细胞增殖的抑制作用[J].中药与临床,2014,5(5):32-35.
[9]Zhu T,Chen R,Yu H,et al.Antitumor effect of a copper(Ⅲ)complex of a coumarin derivative and phenanthroline on lung adenocarcinoma cells and the mechanism of action[J].Mol Med Rep,2014,10(5):2477-2482.
[10]Kostova I,Momekov G.New zirconium(Ⅳ)complexes of coumarins with cytotoxic activity[J].Eur J Med Chem,2006,41(6):717-726.
[11]Achar G,Shahini CR,Patil SA,et al.Sterically modulated silver(Ⅰ)complexes of coumarin substituted benzimidazol-2-ylidenes:Synthesis,crystal structures and evaluation of their antimicrobial and antilung cancer potentials[J].J Inorg Biochem,2018,183:43-57.
[12]Tripathy DR,Roy AS,Dasgupta S.Complex formation of rutin and quercetin with copper alters the mode of inhibition of ribonuclease A[J].FEBS Lett,2011,585(20):3270-3276.
[13]Liu Y,Guo M.Studies on transition metal-quercetin complexes using electrospray ionization tandem mass spectrometry[J].Molecules,2015,20(5):8583-8594.
[14]Horniblow RD,Henesy D,Iqbal TH,et al.Modulation of iron transport,metabolism and reactive oxygen status by quercetin-iron complexes in vitro[J].Mol Nutr Food Res,2017,61(3).
[15]Sun YJ,Huang QQ,Li P,et al.Catalytic dioxygenation of flavonol by M(Ⅱ)-complexes(M=Mn,Fe,Co,Ni,Cu and Zn)-mimicking the M(Ⅱ)-substituted quercetin 2,3-dioxygenase[J].Dalton Trans,2015,44(31):13926-13238.
[16]Dolatabadi JE.Molecular aspects on the interaction of quercetin and its metal complexes with DNA[J].Int J Biol Macromol,2011,48(2):227-233.
[17]Zhou J,Wang LF,Wang JY,et al.Synthesis,characterization,antioxidative and antitumor activities of solid quercetin rare earth(Ⅲ)complexes[J].J Inorg Biochem,2001,83(1):41-48.
[18]Raza A,Xu X,Xia L,et al.Quercetin-iron complex:Synthesis,characterization,antioxidant,DNA binding,DNA cleavage,and antibacterial activity studies[J].J Fluoresc,2016,26(6):2023-2031.
[19]Tan J,Wang B,Zhu L.DNA binding,cytotoxicity,apoptotic inducing activity,and molecular modeling study of quercetin zinc(Ⅱ)complex[J].Bioorg Med Chem,2009,17(2):614-620.
[20]Norma Estefania A,Estela M,Durvanei A,et al.Synthesis,characterization and biological evaluation of Rutin-zinc(Ⅱ)flavonoidmetal complex[J].Chem Biol Interact,2015,239:184-191.
[21]Li C,Huang Q,Xiao J,et al.Preparation of prunella vulgaris polysaccharide-zinc complex and its antiproliferative activity in Hep G2cells[J].Int J Biol Macromol,2016,91:671-679.
[22]张茜,芮瑞,李佩佩,等.草乌多糖金属配合物的制备、表征与抗癌活性研究[J].郑州大学学报(工学版),2016,37(3):36-39.
[23]Martínez Medina JJ,Naso LG,Pérez AL,et al.Antioxidant and anticancer effects and bioavailability studies of the flavonoid baicalin and its oxidovanadium(Ⅳ)complex[J].J Inorg Biochem,2017,166:150-161.
[24]Carter WO,Narayanan PK,Robinson JP.Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells[J].J Leukoc Biol,1994,55(2):253-258.
[25]Islas MS,Naso LG,Lezama L.Insights into the mechanisms underlying the antitumor activity of an oxidovanadium(Ⅳ)compound with the antioxidant naringenin.Albumin binding studies[J].J Inorg Biochem,2015,149:12-24.
[26]Ji Y,Dou YN,Zhao QW,et al.Paeoniflorin suppresses TGF-βmediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway[J].Acta Pharmacol Sin,2016,37(6):794-804.
[27]夏小健,黄蓓.芍药苷在治疗肝癌中作用及其机制的研究进展[J].中南药学,2018,16(2):209-212.
[28]晏雪生,李瀚旻,彭亚琴,等.芍药苷对人肝癌细胞Hep G2凋亡及其调控基因的影响[J].中华中医药学刊,2007,25(7):1346-1347.
[29]Lee SM,Li ML,Tse YC,et al.Paeoniae radix,a Chinese herbal extract,inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway[J].Life Sci,2002,71(19):2267-2277.
[30]Hung JY,Yang CJ,Tsai YM,et al.Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligandmediated apoptotic pathway in human non-small cell lung cancer A549 cells[J].Clin Exp Pharmacol Physiol,2008,35(2):141-147.
[31]Hu S,Chen SM,Li XK,et al.Antitumor effects of chi-shen extract from Salvia miltiorrhiza and Paeoniae radix on human hepatocellular carcinoma cells[J].Acta Pharmacol Sin,2007,28(8):1215-1223.
[32]Li W,Qi Z,Wei Z,et al.Paeoniflorin inhibits proliferation and induces apoptosis of human glioma cells via microRNA-16 upregulation and matrix metalloproteinase-9 downregulation[J].Mol Med Rep,2015,12(2):2735-2740.
[33]Shi L,Teng H,Zhu M,et al.Paeoniflorin inhibits nucleus pulposus cell apoptosis by regulating the expression of Bcl-2 family proteins and caspase-9 in a rabbit model of intervertebral disc degeneration[J].Exp Ther Med,2015,10(1):257-262.
[34]Hu PF,Chen WP,Bao JP,et al.Paeoniflorin inhibits IL-1β-induced chondrocyte apoptosis by regulating the Bax/Bcl-2/caspase-3 signaling pathway[J].Mol Med Rep,2018,17(4):6194-6620.