当归化学成分及抗肿瘤作用机制的研究进展
摘要
近年来,随着天然药物化学分离和提纯技术水平的不断提高,以及药理学研究的深入,当归抗肿瘤活性成分作用机制的研究取得了较大进展。对当归有效成分进行研究后,发现其具有抗肿瘤、调节免疫、造血、抗血小板聚集、平喘和镇痛等多种作用。当归抗肿瘤作用机制主要包括抑制肿瘤血管生成、影响肿瘤细胞周期、抑制肿瘤细胞生长和增殖、诱导肿瘤细胞凋亡、降低黏附性和侵袭力、抑制肿瘤细胞转移、逆转肿瘤耐药和放化疗增敏等。本文通过对国内外相关文献进行系统梳理和归纳,为明确当归抗肿瘤作用机制和新型抗肿瘤药物的研发提供参考。
引文
[1]国家药典委员会.中华人民共和国药典:一部[M].北京:中国医药科技出版社,2015:133-134.
[2]董岩,魏兴国,崔庆新,等.当归挥发油化学成分分析[J].山东中医杂志,2004,23(1):43-45.
[3]李桂生,马成俊,刘志峰,等.超临界CO2萃取法与水蒸气蒸馏法提取当归挥发油的比较[J].中草药,2001,32(7):581-583.
[4]SU Y J,HUANG S Y,NI Y H.Anti-tumor and radiosensitization effects of N-butylidenephthalide on human breast cancer cells[J].Molecules,2018,23(2):1-15.
[5]陶静仪,阮于平,梅其炳,等.当归成分藁本内酯平喘作用的实验研究[J].药学学报,1984,19(8):561-565.
[6]闫升,乔国芳,刘志峰,等.当归油对大鼠离体子宫平滑肌收缩功能的影响[J].中草药,2000,31(8):604-606.
[7]杨庆利,朱玉真,朱文华,等.当归挥发油的药理作用研究[J].兰州医学院学报,1986,3:20-25.
[8]商澎,梅其炳,曹之宪,等.当归多糖组分的高效液相色谱分析[J].中国药学杂志,2000,35(5):332-335.
[9]YANG J,SHAO X,JIANG J,et al.Angelica sinensis polysaccharide inhibits proliferation,migration,and invasion by downregulating microRNA-675 in human neuroblastoma cell line SH-SY5Y[J].Cell Biol Int,2018,42(7):867-876.
[10]马兰芳,卯新民,李兴王,等.当归多糖对造血细胞生成影响的实验研究[J].中华血液杂志,1988,9(5):148-149.
[11]李忠.多糖类成分的药理作用[J].药学通报,1988,23(8):455-458.
[12]秦书芝,赵曦,赵成国,等.当归不同部位中阿魏酸的含量测定[J].中医药导报,2014,20(3):74-75.
[13]GAO J,YU H,GUO W,et al.The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells[J].Cancer Cell Int,2018,18(1):1-9.
[14]李友清,谭秀娟,徐启明,等.阿魏酸钠对犬心脏停跳复苏后脑组织TXB2、6-keto-PGF1α及MDA含量的影响[J].中华麻醉学杂志,1995,15(9):387-390.
[15]孙云,林安平,卞如濂,等.血小板活化因子诱发豚鼠气道高反应性及阿魏酸钠对其的影响[J].中国药理学通报,1996,12(6):519-520.
[16]蒋庭玉.拐芹当归化学成分研究[D].济南:山东大学,2011.
[17]包侠萍.当归不同部位中阿魏酸的含量测定及炮制研究[J].海峡药学,2014,26(6):73-75.
[18]JUNG S Y,CHOI J H,KWON S M,et al.Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function[J].J Cell Biochem,2012,113(5):1478-1487.
[19]CHEN Y,WANG H D,XIA X,et al.Behavioral and biochemical studies of total furoeoumarins from seeds of Psoralea corylifolia in the chronic mild stress model of depression in mice[J].Phytomedicine,2007,14(7/8):523-529.
[20]敖平.什姆干栓翅芹中具有抗免疫缺陷病毒活性的香豆素及呋喃香豆素衍生物[J].国外医学:中医中药分册,2002,24(4):231-232.
[21]李静,魏玉海,秦雪梅,等.基于NMR代谢组学技术的当归不同部位化学成分比较[J].中草药,2017,48(7):1409-1415.
[22]魏于全,赫捷.肿瘤学[M].北京:人民卫生出版社,2015:98-126.
[23]CHEN M C,HSU W L,CHANG W L,et al.Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer[J].Sci Rep,2017,7(1):5376-5386.
[24]MI C,MA J,WANG K S,et al.Imperatorin suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1αvia the mTOR/p70S6K/4E-BP1 and MAPKpathways[J].J Ethnopharmacol,2017,203(5):27-38.
[25]LIN Y L,LAI W L,HARN H J,et al.The methanol extract of Angelica sinensis induces cell apoptosis and suppresses tumor growth in human malignant brain tumors[J].Evid Based Complement Alternat Med,2013,15(2):9-18.
[26]JUNG S Y,CHOI J H,KWON S M,et al.Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function[J].J Cell Biochem,2012,113(5):1478-1487.
[27]TSAI N M,CHEN Y L,LEE C C,et al.The natural compound N-butylidenephthalide derived from Angelica sinensis inhibits malinant brain tumor growth in vitro and in vivo[J].JNeurochem,2006,99(4):1251-1262.
[28]ZHANG W F,YANG Y,LI X,et al.Angelica polysaccharides inhibit the growth and promote the apoptosis of U251 glioma cells in vitro and in vivo[J].Phytomedicine,2017,15(33):21-27.
[29]贾道勇,刘俊,李成鹏,等.当归多糖调控人白血病干细胞衰老的机制研究[J].中国中药杂志,2015,40(1):112-117.
[30]JUNG S,MOON H I,LEE B S,et al.Anti-cancerous effect of cis-khellactone from Angelica amurensis through the induction of three programmed cell deaths[J].Oncotarget,2018,9(24):16744-16757.
[31]CHIU S C,CHIU T L,HUANG S Y.Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis(Danggui)in human bladder cancer cells[J].BMC Complement Altern Med,2017,17(1):523-534.
[32]WANG K S,LV Y,WANG Z,et al.Imperatorin efficiently blocks TNF-α-mediated activation of ROS/PI3K/Akt/NF-κB pathway[J].Oncol Rep,2017,37(6):3397-3404.
[33]ZHENG Y M,SHEN J Z,WANG Y,et al.Anti-oxidant and anti-cancer activities of Angelica dahurica extract via induction of apoptosis in colon cancer cells[J].Phytomedicine,2016,23(11):1267-1274.
[34]KIM W J,LEE M Y,KIM J H,et al.Decursinol angelate blocks transmigration and inflammatory activation of cancer cells through inhibition of PI3K,ERK and NF-κB activation[J].Cancer Lett,2010,296(1):35-42.
[35]KIM J M,NOH E M,KIM M S,et al.Decursin prevents TPA-induced invasion through suppression of PKCα/p38/NF-κB-dependent MMP-9 expression in MCF-7 human breast carcinoma cells[J].Int J Oncol,2014,44(5):1607-1613.
[36]TEW K D,DUTTA S,SCHULTZ M.Inhibitors of glutathione S-transferases as therapeutic agents[J].Adv Drug Deliv Rev,1997,26(2/3):91-104.
[37]HUANG F,LI S,LU X,et al.Two glutathione S-transferase inhibitors from Radix Angelicae Sinensis[J].Phytother Res,2011,25(2):284-289.
[38]QI H,JIANG Z,WANG C,et al.Sensitization of tamoxifenresistant breast cancer cells by Z-ligustilide through inhibiting autophagy and accumulating DNA damages[J].Oncotarget,2017,8(17):29300-29317.
[39]ZENG Q,JIA Y W,XU P L,et al.Quick and selective extraction of Z-ligustilide from Angelica sinensis using magnetic multiwalled carbon nanotubes[J].J Sep Sci,2015,38(24):4269-4275.
[40]MA H,LI L,DOU G,et al.Z-ligustilide restores tamoxifen sensitivity of ERa negative breast cancer cells by reversing MTA1/IFI16/HDACs complex mediated epigenetic repression of ERa[J].Oncotarget,8(17):29328-29345.
[41]CHOI H S,CHO S G,KIM M K,et al.Decursin in Angelica gigas Nakai(AGN)enhances doxorubicin chemosensitivity in NCI/ADR-RES ovarian cancer cells via Inhibition of P-glycoprotein expression[J].Phytother Res,2016,30(12):2020-2026.
[42]SHEHZAD A,ISLAM SU,AHN E M,et al.Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NF-κBpathway[J].Cancer Biol Ther,2016,17(9):985-993.
[2]董岩,魏兴国,崔庆新,等.当归挥发油化学成分分析[J].山东中医杂志,2004,23(1):43-45.
[3]李桂生,马成俊,刘志峰,等.超临界CO2萃取法与水蒸气蒸馏法提取当归挥发油的比较[J].中草药,2001,32(7):581-583.
[4]SU Y J,HUANG S Y,NI Y H.Anti-tumor and radiosensitization effects of N-butylidenephthalide on human breast cancer cells[J].Molecules,2018,23(2):1-15.
[5]陶静仪,阮于平,梅其炳,等.当归成分藁本内酯平喘作用的实验研究[J].药学学报,1984,19(8):561-565.
[6]闫升,乔国芳,刘志峰,等.当归油对大鼠离体子宫平滑肌收缩功能的影响[J].中草药,2000,31(8):604-606.
[7]杨庆利,朱玉真,朱文华,等.当归挥发油的药理作用研究[J].兰州医学院学报,1986,3:20-25.
[8]商澎,梅其炳,曹之宪,等.当归多糖组分的高效液相色谱分析[J].中国药学杂志,2000,35(5):332-335.
[9]YANG J,SHAO X,JIANG J,et al.Angelica sinensis polysaccharide inhibits proliferation,migration,and invasion by downregulating microRNA-675 in human neuroblastoma cell line SH-SY5Y[J].Cell Biol Int,2018,42(7):867-876.
[10]马兰芳,卯新民,李兴王,等.当归多糖对造血细胞生成影响的实验研究[J].中华血液杂志,1988,9(5):148-149.
[11]李忠.多糖类成分的药理作用[J].药学通报,1988,23(8):455-458.
[12]秦书芝,赵曦,赵成国,等.当归不同部位中阿魏酸的含量测定[J].中医药导报,2014,20(3):74-75.
[13]GAO J,YU H,GUO W,et al.The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells[J].Cancer Cell Int,2018,18(1):1-9.
[14]李友清,谭秀娟,徐启明,等.阿魏酸钠对犬心脏停跳复苏后脑组织TXB2、6-keto-PGF1α及MDA含量的影响[J].中华麻醉学杂志,1995,15(9):387-390.
[15]孙云,林安平,卞如濂,等.血小板活化因子诱发豚鼠气道高反应性及阿魏酸钠对其的影响[J].中国药理学通报,1996,12(6):519-520.
[16]蒋庭玉.拐芹当归化学成分研究[D].济南:山东大学,2011.
[17]包侠萍.当归不同部位中阿魏酸的含量测定及炮制研究[J].海峡药学,2014,26(6):73-75.
[18]JUNG S Y,CHOI J H,KWON S M,et al.Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function[J].J Cell Biochem,2012,113(5):1478-1487.
[19]CHEN Y,WANG H D,XIA X,et al.Behavioral and biochemical studies of total furoeoumarins from seeds of Psoralea corylifolia in the chronic mild stress model of depression in mice[J].Phytomedicine,2007,14(7/8):523-529.
[20]敖平.什姆干栓翅芹中具有抗免疫缺陷病毒活性的香豆素及呋喃香豆素衍生物[J].国外医学:中医中药分册,2002,24(4):231-232.
[21]李静,魏玉海,秦雪梅,等.基于NMR代谢组学技术的当归不同部位化学成分比较[J].中草药,2017,48(7):1409-1415.
[22]魏于全,赫捷.肿瘤学[M].北京:人民卫生出版社,2015:98-126.
[23]CHEN M C,HSU W L,CHANG W L,et al.Antiangiogenic activity of phthalides-enriched Angelica Sinensis extract by suppressing WSB-1/pVHL/HIF-1α/VEGF signaling in bladder cancer[J].Sci Rep,2017,7(1):5376-5386.
[24]MI C,MA J,WANG K S,et al.Imperatorin suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1αvia the mTOR/p70S6K/4E-BP1 and MAPKpathways[J].J Ethnopharmacol,2017,203(5):27-38.
[25]LIN Y L,LAI W L,HARN H J,et al.The methanol extract of Angelica sinensis induces cell apoptosis and suppresses tumor growth in human malignant brain tumors[J].Evid Based Complement Alternat Med,2013,15(2):9-18.
[26]JUNG S Y,CHOI J H,KWON S M,et al.Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function[J].J Cell Biochem,2012,113(5):1478-1487.
[27]TSAI N M,CHEN Y L,LEE C C,et al.The natural compound N-butylidenephthalide derived from Angelica sinensis inhibits malinant brain tumor growth in vitro and in vivo[J].JNeurochem,2006,99(4):1251-1262.
[28]ZHANG W F,YANG Y,LI X,et al.Angelica polysaccharides inhibit the growth and promote the apoptosis of U251 glioma cells in vitro and in vivo[J].Phytomedicine,2017,15(33):21-27.
[29]贾道勇,刘俊,李成鹏,等.当归多糖调控人白血病干细胞衰老的机制研究[J].中国中药杂志,2015,40(1):112-117.
[30]JUNG S,MOON H I,LEE B S,et al.Anti-cancerous effect of cis-khellactone from Angelica amurensis through the induction of three programmed cell deaths[J].Oncotarget,2018,9(24):16744-16757.
[31]CHIU S C,CHIU T L,HUANG S Y.Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis(Danggui)in human bladder cancer cells[J].BMC Complement Altern Med,2017,17(1):523-534.
[32]WANG K S,LV Y,WANG Z,et al.Imperatorin efficiently blocks TNF-α-mediated activation of ROS/PI3K/Akt/NF-κB pathway[J].Oncol Rep,2017,37(6):3397-3404.
[33]ZHENG Y M,SHEN J Z,WANG Y,et al.Anti-oxidant and anti-cancer activities of Angelica dahurica extract via induction of apoptosis in colon cancer cells[J].Phytomedicine,2016,23(11):1267-1274.
[34]KIM W J,LEE M Y,KIM J H,et al.Decursinol angelate blocks transmigration and inflammatory activation of cancer cells through inhibition of PI3K,ERK and NF-κB activation[J].Cancer Lett,2010,296(1):35-42.
[35]KIM J M,NOH E M,KIM M S,et al.Decursin prevents TPA-induced invasion through suppression of PKCα/p38/NF-κB-dependent MMP-9 expression in MCF-7 human breast carcinoma cells[J].Int J Oncol,2014,44(5):1607-1613.
[36]TEW K D,DUTTA S,SCHULTZ M.Inhibitors of glutathione S-transferases as therapeutic agents[J].Adv Drug Deliv Rev,1997,26(2/3):91-104.
[37]HUANG F,LI S,LU X,et al.Two glutathione S-transferase inhibitors from Radix Angelicae Sinensis[J].Phytother Res,2011,25(2):284-289.
[38]QI H,JIANG Z,WANG C,et al.Sensitization of tamoxifenresistant breast cancer cells by Z-ligustilide through inhibiting autophagy and accumulating DNA damages[J].Oncotarget,2017,8(17):29300-29317.
[39]ZENG Q,JIA Y W,XU P L,et al.Quick and selective extraction of Z-ligustilide from Angelica sinensis using magnetic multiwalled carbon nanotubes[J].J Sep Sci,2015,38(24):4269-4275.
[40]MA H,LI L,DOU G,et al.Z-ligustilide restores tamoxifen sensitivity of ERa negative breast cancer cells by reversing MTA1/IFI16/HDACs complex mediated epigenetic repression of ERa[J].Oncotarget,8(17):29328-29345.
[41]CHOI H S,CHO S G,KIM M K,et al.Decursin in Angelica gigas Nakai(AGN)enhances doxorubicin chemosensitivity in NCI/ADR-RES ovarian cancer cells via Inhibition of P-glycoprotein expression[J].Phytother Res,2016,30(12):2020-2026.
[42]SHEHZAD A,ISLAM SU,AHN E M,et al.Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NF-κBpathway[J].Cancer Biol Ther,2016,17(9):985-993.