吴茱萸碱的现代药理研究进展
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摘要
吴茱萸碱(evodiamine, Evo)是吴茱萸中重要的生物碱成分,其主要药理作用为抗肿瘤、抗炎镇痛、抑菌、调节内分泌、降血脂、调节平滑肌细胞等。吴茱萸碱可通过调控信号通路和引发细胞周期阻滞而达到抗肿瘤作用,包括JAK2/STAT3信号通路、Wnt/β-catenin信号通路、PI3K/Akt和mTOR等信号通路,同时吴茱萸碱可以将肿瘤细胞阻滞于G0/G1期和G2/M期。这些研究为靶向治疗肿瘤提供了可行性方案,为治疗其他相关性疾病提供参考。
Evodiamine(Evo) is an important alkaloid component in E. sinensis. Its main pharmacological effects are anti-tumor, anti-inflammatory and analgesic, antibacterial, regulating endocrine, hypolipidemicand regulating smooth muscle cells effects. Evodiamine can achieve antitumor effects by regulating signal pathways and triggering cell cycle arrest, including JAK2/STAT3 signaling pathway, Wnt/β-catenin signaling pathway, PI3 K/Akt and mTOR signaling pathways. And evodiamine can treat tumor cells,blocked in G0/G1 and G2/M phases. These studies provide a feasible solution for the targeted treatment of tumors and provide references for the treatment of other related diseases.
Evodiamine(Evo) is an important alkaloid component in E. sinensis. Its main pharmacological effects are anti-tumor, anti-inflammatory and analgesic, antibacterial, regulating endocrine, hypolipidemicand regulating smooth muscle cells effects. Evodiamine can achieve antitumor effects by regulating signal pathways and triggering cell cycle arrest, including JAK2/STAT3 signaling pathway, Wnt/β-catenin signaling pathway, PI3 K/Akt and mTOR signaling pathways. And evodiamine can treat tumor cells,blocked in G0/G1 and G2/M phases. These studies provide a feasible solution for the targeted treatment of tumors and provide references for the treatment of other related diseases.
引文
[1] Jun Huang, Zhen-Hua, Chen Chun-Mei Ren, et al. Antiproliferation effect of evodiamine in human colon cancer cells is associated with IGF-1/HIF-1α downregulation[J]. Oncology Reports, 2015, 34:3203-3211.
[2] Dongmei Yang, Li Li, Shanjun Qian, et al. Evodiamine ameliorates liver fibrosis in rats via TGF-β1/Smad signaling pathway[J]. Journal of Natural Medicines, 2018,72(1):145-154.
[3] 孟子钧. 吴茱萸碱抑制人骨肉瘤细胞143B增殖与PI3K/Akt信号关系的研究[D].重庆:重庆医科大学,2015.
[4] Zhenzhen Wen, Shujiong Feng, Lijuan Wei, et al. Evodiamine, a novel inhibitor of the Wnt pathway, inhibits the self-renewal of gastric cancer stem cells[J]. International Journal of Molecular Medicine, 2015, 36:1657-1663.
[5] 陈辉,王兆洪,陈龙,等.吴茱萸碱对人胰腺癌SW1990细胞株体内外增殖及凋亡的影响[J].温州医科大学学报,2017,47(6):431-434,440.
[6] Hua Yu, Heehyoung Lee, Andreas Herrmann, et al. Revisiting STAT3 signalling in cancer: new and unexpected biological functions[J]. Nature Reviews Cancer volume, 2014, 14: 736-746.
[7] Zhao LC, Li J, Liao K, Luo N, et al.Evodiamine Induces Apoptosis and Inhibits Migration of HCT-116 Human Colorectal Cancer Cells[J].Int J Mol Sci, 2015,16(11):27411-27421.
[8] Lv-Cui Zhao, Jing Li, Ke Liao,et al. Evodiamine Induces Apoptosis and Inhibits Migration of HCT-116 Human Colorectal Cancer Cells[J]. Int. J. Mol. Sci, 2015, 16(11): 27411-27421.
[9] 赵绿翠,廖科,李科琼,等.吴茱萸碱调控人结肠癌HCT-116细胞中JAK2/STAT3信号通路的机制研究[J].中国药理学通报,2015,31(10):1394-1398.
[10] Yang J, Cai X, Lu W, et al. Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells[J]. Cancer Lett, 2013,328(2):243-251.
[11] Van Camp JK, Beckers S, Zegers D, et al. Wnt signaling and the control of human stem cell fate[J]. Stem Cell Rev, 2014, 10:207-229.
[12] Che-Yuan Hu, Hung-Tsung Wu,Yu-Chu Su, et al. Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway[J]. Molecules, 2017, 22(7): 1175.
[13] 王元惠,周振华.吴茱萸碱对大肠癌细胞株HT29恶性生物学行为及Wnt/β-catenin信号通路的调控作用[J].海南医学院学报,2016,22(8):729-731,735.
[14] 祁迪,谭群友,王如文,等.吴茱萸碱抑制PI3K/AKT通路诱导小细胞肺癌H1688和H446细胞凋亡[J].第三军医大学学报,2016,38(4):330-337.
[15] Zhongchuan Lv, Dawei Zhao, Ruihua Liu, et al. Evodiamine inhibits proliferation of human papillary thyroid cancer cell line K1 by regulating of PI3K/Akt signaling pathway[J]. Int J Clin Exp Med, 2016, 9(8):15216-15225.
[16] 陈振华,任春美,万仁圣,等.PI3K/Akt信号与吴茱萸碱抑制人结肠癌细胞增殖的关系研究[J].第三军医大学学报,2016,38(5):492-495.
[17] Xiaodong Bai, Hai Meng, Lifeng Ma,et al.Inhibitory effects of evodiamine on human osteosarcoma cell proliferation and apoptosis[J].Oncology Letters, 2015, 9(2): 801-805.
[18] FanYang,LeShi,TaoLiang,et al.Anti-tumor effect of evodiamine by inducing Akt-mediated apoptosis in hepatocellular carcinoma[J].Biochemical and Biophysical Research Communications,2017, 485(1):54-61.
[19] Tao Zhang, Shanna Qu, Qi Shi, et al. Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1[J].Int. J. Mol. Sci, 2014, 15(2): 3154-3171.
[20] Liu X, Yang L, Bi Y, et al. Effect of evodiamine in inducing apoptosis of gastric cancer SGC-7901 cells through mTOR signal pathway[J].Europe PMC, 2015, 40(16):3262-3266.
[21] 刘鑫,杨丽,毕瑩,等.Evo作用mTOR信号通路引起胃癌SGC-7901细胞凋亡的研究[J].中国中药杂志,2015,40(16):3262-3266.
[22] Hua Sui,Li-Hong Zhou,Ya-Li Zhang,et al.Evodiamine Suppresses ABCG2 Mediated Drug Resistance by Inhibiting p50/p65 NF-κB Pathway in Colorectal Cancer[J].Journal of cellular biochemical,2016,117(6):1471-1481.
[23] Chih-Chiang Chien, Ming-Shun Wu, Shing-Chuan Shen, et al.Activation of JNK Contributes to Evodiamine-Induced Apoptosis and G2/M Arrest in Human Colorectal Carcinoma Cells: A Structure-Activity Study of Evodiamine[J].Plos one, 2014,9(6):e99729.
[24] C Fang, J Zhang, D Qi, et al. Evodiamine Induces G2/M Arrest and Apoptosis via Mitochondrial and Endoplasmic Reticulum Pathways in H446 and H1688 Human Small-Cell Lung Cancer Cells[J].Plos one,2014,9(12):e115204.
[25] 常金荣,王建华,邝枣园,等.从miRNA-17-92途径探讨小檗碱和吴茱萸碱对大肠癌HT29细胞周期调控机制[J].中药药理与临床,2014,30(3):19-22.
[26] Wen-Shin Wu, Chih-Chiang Chien, Kao-Hui Liu, et al. Evodiamine Prevents Glioma Growth, Induces Glioblastoma Cell Apoptosis and Cell Cycle Arrest through JNK Activation[J].Am. J. Chin. Med,2017,45(4):479-481.
[27] Chung-Sheng Shi, Jhy-Ming Li, Chin-Ching Chin,et al. Evodiamine Induces Cell Growth Arrest, Apoptosis and Suppresses Tumorigenesis in Human Urothelial Cell Carcinoma Cells[J].Anticancer Research , 2017, 37(3):1149-1159.
[28] Zhang-Feng Zhong, Wen Tan. Anti-proliferative activity and cell cycle arrest induced by evodiamine on paclitaxel-sensitive and -resistant human ovarian cancer cells[M].Scientific Reports,2015.
[29] 袁龙,陈益,刘泽洪,等.吴茱萸碱抑制HDAC6促进人白血病K562细胞周期阻滞和凋亡的机制研究[J].中草药,2016,47(17):3044-3050.
[30] Jia Du, Yang Sun, Yi -Yu Lu, et al. Berberine and Evodiamine Act Synergistically Against Human Breast Cancer MCF-7 Cells by Inducing Cell Cycle Arrest and Apoptosis[J].Anticancer Research, 2017,37(11):6141-6151.
[31] 陶兆燕,李涓,盛蓉,等.吴茱萸碱分散片降血尿酸及抗炎、镇痛的实验研究[J].时珍国医国药,2013,24(5):1147-1148.
[32] E Iwaoka, S Wang, N Matsuyoshi, et al. Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels[J].Journal of Natural Medicines, 2016, 70(1): 1-7.
[33] Qiulan Lv, Yun Xue, Guo dong Li,et al. Beneficial effects of evodiamine on P2X4-mediated inflammatory injury of human umbilical vein endothelial cells due to high glucose[J].International Immunopharmacology, 2015,28(2):1044-1049.
[34] 范霞. 吴茱萸碱抗炎机制的初步研究[C]//第十届全国中西医结合灾害医学学术大会江苏省中西医结合学会灾害医学、重症医学专业委员会成立大会暨健康产业成果展示洽谈会学术论文集.中国中西医结合学会、中国中西医结合学会灾害医学专业委员会、江苏省中西医结合学会,2014:1.
[35] 章玲宾,潘晨,张宁,等.普瑞巴林联合吴茱萸碱对神经病理性疼痛大鼠细胞因子和T细胞的影响[J].中国中西医结合外科杂志,2016,22(4):350-354.
[36] 魏宏,林晶晶,王静,等.小檗碱吴茱萸碱配伍的降脂作用与上调LXRα和PPARγ蛋白表达的研究[J].湖南中医杂志,2017,33(2):126-129.
[37] 李雯婧,李国军,王智,等.吴茱萸挥发油抑菌活性及其化学成分研究[J].湖南农业科学,2014(10):16-18.
[38] 张卫,高燕飞,张敏.吴茱萸提取物和挥发油对牙龈卟啉单胞菌的影响[J].时珍国医国药,2013,24(9):2136-2137.
[39] 王明华,邵明亮,高子怡,等.吴茱萸多酚的酶法提取工艺及其抗氧化抑菌活性[J].北方园艺,2017(22):126-131.
[40] 吴方评,金苹,蒲洪.吴茱萸碱和吴茱萸次碱含药血清抑菌活性研究[J].中医药导报,2016,22(24):47-49.
[41] Mei-Ling Jiang, Zhi-Xian Zhang,Yun-Zhan Li, et al.Antidepressant-like effect of evodiamine on chronic unpredictable mild stress rats[J].Neuroscience Letters, 2015, 588(19):154-158.
[42] 李晓亚,刘金玉,穆玉雪,等.吴茱萸碱对大鼠离体子宫平滑肌的舒张作用及机制研究[J].中国药师,2017,20(10):1713-1717.
[43] 杜芳,姚珍薇.吴茱萸碱对多囊卵巢综合征模型大鼠的影响[J].激光杂志,2013,34(2):86-88.
[44] Hitoshi Yamashita, Tatsuya Kusudo, Tamaki Takeuchi, et al. Dietary supplementation with evodiamine prevents obesity and improves insulin resistance in ageing mice[J].Journal of Functional Foods, 2015, 19:320-329.
[45] 张秋方,杨奕樱,陈洪,等.吴茱萸碱对高脂血症小鼠血脂水平及血液黏稠度的影响[J].河南中医,2017,37(1):72-74.
[46] 周昕,魏宏,沈涛,等.小檗碱与吴茱萸碱配伍对高胆固醇血症大鼠小肠ACAT2、ApoB48和NPC1L1表达的影响[J].中成药,2017,39(10):1993-1999.
[47] 魏宏,林晶晶,王静,等.小檗碱吴茱萸碱配伍的降脂作用与上调LXRα和PPARγ蛋白表达的研究[J].湖南中医杂志,2017,33(2):126-129.
[48] Xin Zhou, Fengying Ren, Hong Wei,et al. Combination of berberine and evodiamine inhibits intestinal cholesterol absorption in high fat diet induced hyperlipidemic rats[J].Lipids in Health and Disease, 2017, 16:239.
[49] Curcio A, Torella D, Indolfi C. Mechanisms of smooth muscle cell proliferation and endothelial regeneration after vascular injury and stenting: Approach to therapy[J]. Circ J, 2011(75):1287-1296.
[50] Xie Ge, Si-Yu Chen, Mei Liu,et al. Evodiamine inhibits PDGF BB induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress[J]. Molecular Medicine Reports,2016,14(5):4551-4558.
[51] 侯化化,徐洋,李强,等.吴茱萸碱抑制大鼠血管平滑肌细胞增殖及对细胞外信号调节激酶-1表达的影响[J].中国现代医学杂志,2014,24(35):5-9.
[52] 侯化化,张婧怡,林淑娴,等.吴茱萸碱抑制血管紧张素Ⅱ致大鼠血管平滑肌细胞增殖的研究[J].华西药学杂志,2014,29(6):645-647.
[2] Dongmei Yang, Li Li, Shanjun Qian, et al. Evodiamine ameliorates liver fibrosis in rats via TGF-β1/Smad signaling pathway[J]. Journal of Natural Medicines, 2018,72(1):145-154.
[3] 孟子钧. 吴茱萸碱抑制人骨肉瘤细胞143B增殖与PI3K/Akt信号关系的研究[D].重庆:重庆医科大学,2015.
[4] Zhenzhen Wen, Shujiong Feng, Lijuan Wei, et al. Evodiamine, a novel inhibitor of the Wnt pathway, inhibits the self-renewal of gastric cancer stem cells[J]. International Journal of Molecular Medicine, 2015, 36:1657-1663.
[5] 陈辉,王兆洪,陈龙,等.吴茱萸碱对人胰腺癌SW1990细胞株体内外增殖及凋亡的影响[J].温州医科大学学报,2017,47(6):431-434,440.
[6] Hua Yu, Heehyoung Lee, Andreas Herrmann, et al. Revisiting STAT3 signalling in cancer: new and unexpected biological functions[J]. Nature Reviews Cancer volume, 2014, 14: 736-746.
[7] Zhao LC, Li J, Liao K, Luo N, et al.Evodiamine Induces Apoptosis and Inhibits Migration of HCT-116 Human Colorectal Cancer Cells[J].Int J Mol Sci, 2015,16(11):27411-27421.
[8] Lv-Cui Zhao, Jing Li, Ke Liao,et al. Evodiamine Induces Apoptosis and Inhibits Migration of HCT-116 Human Colorectal Cancer Cells[J]. Int. J. Mol. Sci, 2015, 16(11): 27411-27421.
[9] 赵绿翠,廖科,李科琼,等.吴茱萸碱调控人结肠癌HCT-116细胞中JAK2/STAT3信号通路的机制研究[J].中国药理学通报,2015,31(10):1394-1398.
[10] Yang J, Cai X, Lu W, et al. Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells[J]. Cancer Lett, 2013,328(2):243-251.
[11] Van Camp JK, Beckers S, Zegers D, et al. Wnt signaling and the control of human stem cell fate[J]. Stem Cell Rev, 2014, 10:207-229.
[12] Che-Yuan Hu, Hung-Tsung Wu,Yu-Chu Su, et al. Evodiamine Exerts an Anti-Hepatocellular Carcinoma Activity through a WWOX-Dependent Pathway[J]. Molecules, 2017, 22(7): 1175.
[13] 王元惠,周振华.吴茱萸碱对大肠癌细胞株HT29恶性生物学行为及Wnt/β-catenin信号通路的调控作用[J].海南医学院学报,2016,22(8):729-731,735.
[14] 祁迪,谭群友,王如文,等.吴茱萸碱抑制PI3K/AKT通路诱导小细胞肺癌H1688和H446细胞凋亡[J].第三军医大学学报,2016,38(4):330-337.
[15] Zhongchuan Lv, Dawei Zhao, Ruihua Liu, et al. Evodiamine inhibits proliferation of human papillary thyroid cancer cell line K1 by regulating of PI3K/Akt signaling pathway[J]. Int J Clin Exp Med, 2016, 9(8):15216-15225.
[16] 陈振华,任春美,万仁圣,等.PI3K/Akt信号与吴茱萸碱抑制人结肠癌细胞增殖的关系研究[J].第三军医大学学报,2016,38(5):492-495.
[17] Xiaodong Bai, Hai Meng, Lifeng Ma,et al.Inhibitory effects of evodiamine on human osteosarcoma cell proliferation and apoptosis[J].Oncology Letters, 2015, 9(2): 801-805.
[18] FanYang,LeShi,TaoLiang,et al.Anti-tumor effect of evodiamine by inducing Akt-mediated apoptosis in hepatocellular carcinoma[J].Biochemical and Biophysical Research Communications,2017, 485(1):54-61.
[19] Tao Zhang, Shanna Qu, Qi Shi, et al. Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1[J].Int. J. Mol. Sci, 2014, 15(2): 3154-3171.
[20] Liu X, Yang L, Bi Y, et al. Effect of evodiamine in inducing apoptosis of gastric cancer SGC-7901 cells through mTOR signal pathway[J].Europe PMC, 2015, 40(16):3262-3266.
[21] 刘鑫,杨丽,毕瑩,等.Evo作用mTOR信号通路引起胃癌SGC-7901细胞凋亡的研究[J].中国中药杂志,2015,40(16):3262-3266.
[22] Hua Sui,Li-Hong Zhou,Ya-Li Zhang,et al.Evodiamine Suppresses ABCG2 Mediated Drug Resistance by Inhibiting p50/p65 NF-κB Pathway in Colorectal Cancer[J].Journal of cellular biochemical,2016,117(6):1471-1481.
[23] Chih-Chiang Chien, Ming-Shun Wu, Shing-Chuan Shen, et al.Activation of JNK Contributes to Evodiamine-Induced Apoptosis and G2/M Arrest in Human Colorectal Carcinoma Cells: A Structure-Activity Study of Evodiamine[J].Plos one, 2014,9(6):e99729.
[24] C Fang, J Zhang, D Qi, et al. Evodiamine Induces G2/M Arrest and Apoptosis via Mitochondrial and Endoplasmic Reticulum Pathways in H446 and H1688 Human Small-Cell Lung Cancer Cells[J].Plos one,2014,9(12):e115204.
[25] 常金荣,王建华,邝枣园,等.从miRNA-17-92途径探讨小檗碱和吴茱萸碱对大肠癌HT29细胞周期调控机制[J].中药药理与临床,2014,30(3):19-22.
[26] Wen-Shin Wu, Chih-Chiang Chien, Kao-Hui Liu, et al. Evodiamine Prevents Glioma Growth, Induces Glioblastoma Cell Apoptosis and Cell Cycle Arrest through JNK Activation[J].Am. J. Chin. Med,2017,45(4):479-481.
[27] Chung-Sheng Shi, Jhy-Ming Li, Chin-Ching Chin,et al. Evodiamine Induces Cell Growth Arrest, Apoptosis and Suppresses Tumorigenesis in Human Urothelial Cell Carcinoma Cells[J].Anticancer Research , 2017, 37(3):1149-1159.
[28] Zhang-Feng Zhong, Wen Tan. Anti-proliferative activity and cell cycle arrest induced by evodiamine on paclitaxel-sensitive and -resistant human ovarian cancer cells[M].Scientific Reports,2015.
[29] 袁龙,陈益,刘泽洪,等.吴茱萸碱抑制HDAC6促进人白血病K562细胞周期阻滞和凋亡的机制研究[J].中草药,2016,47(17):3044-3050.
[30] Jia Du, Yang Sun, Yi -Yu Lu, et al. Berberine and Evodiamine Act Synergistically Against Human Breast Cancer MCF-7 Cells by Inducing Cell Cycle Arrest and Apoptosis[J].Anticancer Research, 2017,37(11):6141-6151.
[31] 陶兆燕,李涓,盛蓉,等.吴茱萸碱分散片降血尿酸及抗炎、镇痛的实验研究[J].时珍国医国药,2013,24(5):1147-1148.
[32] E Iwaoka, S Wang, N Matsuyoshi, et al. Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels[J].Journal of Natural Medicines, 2016, 70(1): 1-7.
[33] Qiulan Lv, Yun Xue, Guo dong Li,et al. Beneficial effects of evodiamine on P2X4-mediated inflammatory injury of human umbilical vein endothelial cells due to high glucose[J].International Immunopharmacology, 2015,28(2):1044-1049.
[34] 范霞. 吴茱萸碱抗炎机制的初步研究[C]//第十届全国中西医结合灾害医学学术大会江苏省中西医结合学会灾害医学、重症医学专业委员会成立大会暨健康产业成果展示洽谈会学术论文集.中国中西医结合学会、中国中西医结合学会灾害医学专业委员会、江苏省中西医结合学会,2014:1.
[35] 章玲宾,潘晨,张宁,等.普瑞巴林联合吴茱萸碱对神经病理性疼痛大鼠细胞因子和T细胞的影响[J].中国中西医结合外科杂志,2016,22(4):350-354.
[36] 魏宏,林晶晶,王静,等.小檗碱吴茱萸碱配伍的降脂作用与上调LXRα和PPARγ蛋白表达的研究[J].湖南中医杂志,2017,33(2):126-129.
[37] 李雯婧,李国军,王智,等.吴茱萸挥发油抑菌活性及其化学成分研究[J].湖南农业科学,2014(10):16-18.
[38] 张卫,高燕飞,张敏.吴茱萸提取物和挥发油对牙龈卟啉单胞菌的影响[J].时珍国医国药,2013,24(9):2136-2137.
[39] 王明华,邵明亮,高子怡,等.吴茱萸多酚的酶法提取工艺及其抗氧化抑菌活性[J].北方园艺,2017(22):126-131.
[40] 吴方评,金苹,蒲洪.吴茱萸碱和吴茱萸次碱含药血清抑菌活性研究[J].中医药导报,2016,22(24):47-49.
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