竹节参皂苷Ⅳa及其衍生物的药理活性及作用机制研究进展
摘要
目的:了解竹节参皂苷Ⅳa及其衍生物药理活性和作用机制的研究进展,为其进一步开发利用提供参考。方法:以"竹节参""竹节参皂苷""竹节参皂苷Ⅳa""衍生物""药理活性""Chikusetsusaponin""ChikusetsusaponinⅣa""Panacis Japonici""Derivative""Pharmacological activity"等为关键词,组合查询1989年1月-2017年12月发表并收录于中国知网、万方、维普、Pub Med、Web of Science等数据库的相关文献,就竹节参皂苷Ⅳa及其衍生物的种类、药理活性、作用机制及靶点进行归纳与总结。结果与结论:共检索得到相关文献489篇,其中有效文献43篇。具药理活性的相关化合物包括竹节参皂苷Ⅳa、竹节参皂苷Ⅳa甲酯、竹节参皂苷Ⅳa丁酯、去葡萄糖竹节参皂苷Ⅳa,主要药理活性为保护心/脑、调节代谢、抗炎、抗凝血、抗肿瘤、抗病毒等。其相关作用机制及靶点主要包括激活沉默信息调节因子2相关酶1/细胞外调节蛋白激酶1/2/突触后膜骨架蛋白Homer1a途径,增强机体清除氧自由基的能力、降低心肌细胞膜脂质过氧化的程度,上调同源丢失性磷酸酶张力蛋白、下调核因子κB的表达,调节Ca2+、K+、Na+等离子的跨膜转运,促进糖原合酶激酶3β的磷酸化,抑制蛋白激酶C的磷酸化,抑制细胞外因子/β-联蛋白信号通路,抑制炎症因子表达,抑制血小板聚集,诱导肿瘤细胞周期停滞及凋亡,导致病毒直接失活或抑制子代病毒释放等。目前尚缺乏竹节参皂苷Ⅳa及其衍生物单体药理活性及作用机制的系统性深入研究,同时上述化合物是否具有其他药理作用、其药动学特征及剂型研发等均有待进一步探索。
引文
[1]武秋爽,陈平,张庆文.竹节参化学成分、药理活性及分析方法研究进展[J].亚太传统医药,2016,12(6):46-54.
[2]李成全,周健,徐洲,等.太白楤木的化学成分及药理作用研究进展[J].中南药学,2017,15(10):1401-1409.
[3]张小鸿,徐先祥.竹节参皂苷药理作用研究进展[J].天然产物研究与开发,2013(25):153-156、78.
[4]宋小妹,李林,杨光明,等.不同产地珠子参中竹节参皂苷Ⅳa含量测定[J].中国中药杂志,2010,35(7):885-887.
[5]范妤,郭东艳,宋强,等.太白楤木活性成分及其药理作用研究进展[J].现代中西医结合杂志,2014,23(2):221-223.
[6]LEE HJ,SHIN JS,LEE WS,et al.ChikusetsusaponinⅣa methyl ester isolated from the roots of Achyranthes japonica suppresses LPS-Induced i NOS,TNF-α,IL-6,and IL-1βexpression by NF-k B and AP-1 inactivation[J].Biol Pharm Bull,2016,39(5):657-664.
[7]南京中医药大学.中药大辞典[M].上海:上海科学技术出版社,2006:1-3875.
[8]许苗苗,张旋,宋蓓,等.珠子参抗肝损伤药效的物质基础研究[J].西北药学杂志,2014,29(5):486-489.
[9]杜原瑗,陈骞虎,贾绍辉,等.牛膝竹节参皂苷与杜仲松脂醇二葡萄糖苷联合治疗骨质疏松性骨折的实验研究[J].中国中医骨伤科杂志,2015,23(6):9-13.
[10]WENG Y,YU L,CUI J,et al.Antihyperglycemic,hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats[J].J Ethnopharmcol,2014,152(3):553-560.
[11]魏娜,袁丁,徐媛青,等.竹节参总皂苷对大鼠心肌梗死的保护作用[J].中药药理与临床,2013,29(3):75-78.
[12]闫佳佳,伍晓晓,段佳林,等.楤木皂苷对大鼠心肌缺血/再灌注损伤的保护作用[J].现代生物医学进展,2015,15(15):2829-2832.
[13]CAO Y,GU C,ZHAO F,et al.Therapeutic effects of cyathula officinalis kuan and its active fraction on acute blood stasis rat model and identification constituents by HPLC-QTOF/MS/MS[J].Pharmacogn Mag,2017,13(52):693-701.
[14]HE H,XU J,XU Y,et al.Cardioprotective effects of saponins from Panax japonicus on acute myocardial ischemia against oxidative stress-triggered damage and cardiac cell death in rats[J].J Ethnopharmacol,2012,140(1):73-82.
[15]LI Y,ZHANG T,CUI J,et al.Chikusetsu saponinⅣa regulates glucose uptake and fatty acid oxidation;implications in antihyperglycemic and hypolipidemic effects[J].JPharm Pharmacol,2015,67(7):997-1007.
[16]CHEN X,WU QS,MENG FC,et al.ChikusetsusaponinⅣa methyl ester induces G1cell cycle arrest,triggers apoptosis and inhibits migration and invasion in ovarian cancer cells[J].Phytomedicine,2017.DOI:10.1016/j.phymed.2017.05.003.
[17]YANG J,QIAN S,CAI X,et al.ChikusetsusaponinⅣa butyl ester(CS-Ⅳa-Be):a novel IL6R antagonist,inhibits IL6/STAT3 signaling pathway and induces cancer cell apoptosis[J].Mol Cancer Ther,2016,15(6):1190-1200.
[18]GUSTAFSSON AB,GOTTLIEB RA.Mechanisms of apoptosis in the heart[J].J Clin Immunol,2003,23(6):447-459.
[19]WANG SH,SHIH YL,KO WC,et al.Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway[J].Cell Mol Life Sci,2008,65(22):3640-3652.
[20]DUAN J,YIN Y,WEI G,et al.Chikusetsu saponinⅣa confers cardioprotection via SIRT1/ERK1/2 and Homer1a pathway[J].Sci Rep,2015.DOI:10.1038/srep18123.
[21]孙桂波,徐惠波,温富春,等.去葡萄糖竹节参皂苷Ⅳa对缺氧复氧心肌细胞损伤的保护作用[J].中国药理学与毒理学杂志,2005,19(6):424-427.
[22]GUO J,LI L,WU YJ,et al.Inhibitory effects of Brazilin on the vascular smooth muscle cell proliferation and migration induced by PDGF-BB[J].Am J Chin Med,2013,41(6):1283-1296.
[23]杨冬梅,聂娟,孙四玉,等.竹节参皂苷Ⅳa甲酯对血管紧张素Ⅱ诱导的血管平滑肌细胞增殖影响及机制研究[J].中国临床药理学与治疗学,2016,21(8):873-877.
[24]薛慧,王卫东.竹节参在治疗心脑血管病方面的研究进展[J].医学理论与实践,2008,21(11):127-1280.
[25]孙桂波,徐惠波,温富春,等.去葡萄糖竹节参皂苷Ⅳa抗实验性心律失常作用[J].中国药理学与毒理学杂志,2006,20(5):377-381.
[26]孙桂波,徐惠波,温富春,等.去葡萄糖竹节参皂苷Ⅳa对心肌电生理特性的影响[J].中国药理学通报,2006,22(11):1407-1408.
[27]DUAN J,YIN Y,CUI J,et al.Chikusetsu SaponinⅣa ameliorates cerebral ischemia reperfusion injury in diabetic mice via adiponectin-mediated AMPK/GSK-3βpathway in vivo and in vitro[J].Mol Neurobiol,2016,53(1):728-743.
[28]FANG X,HAN Q,LI S,et al.Chikusetsu saponinⅣa attenuates isoflurane-induced neurotoxicity and cognitive deficits via SIRT1/ERK1/2 in developmental rats[J].Am JTransl Res,2017,9(9):4288-4299.
[29]CUI J,XI M,LI Y,et al.Insulinotropic effect of chikusetsu saponinⅣa in diabetic rats and pancreaticβ-cells[J].JEthnopharmacology,2015.DOI:10.1016/j.jep.2015.02.032.
[30]YUAN C,LIU C,WANG T,et al.Chikusetsu saponinⅣa ameliorates high fat diet-induced inflammation in adipose tissue of mice through inhibition of NLRP3 inflammasome activation and NF-κB signaling[J].Oncotarget,2017,8(19):31023-31040.
[31]潘茂兴,顿耀艳,陈静,等.竹节参皂苷Ⅳa对高脂饮食小鼠小肠干细胞及其微环境Wnt/β-catenin信号通路的影响[J].中药材,2017,40(6):1415-1419.
[32]WANG H,QI J,LI L,et al.Inhibitory effects of chikusetsusaponinⅣa on lipopolysaccharide-induced pro-inflammatory responses in THP-1 cells[J].Int J Immunopathol Pharmacol,2015,28(3):308-317.
[33]DAHMER T,BERGER M,BARLETTE AG,et al.Antithrombotic effect of chikusetsusaponinⅣa isolated from Ilex paraguariensis(Maté)[J].J Med Food,2012,15(12):1073-1080.
[34]ZHU W,TIAN F,LIU L,et al.Chikusetsu(CHI)triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species(ROS)production[J].Biomed Pharmacother,2017.DOI:10.1016/j.biopha.2017.03.050.
[35]LEE KM,YUN JH,LEE DH,et al.ChikusetsusaponinⅣa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation ofβ-catenin in HCT116 cells[J].Biochem Biophys Res Commun,2015,459(4):591-596.
[36]YOO HH,KWON SW,PARK JH.The cytotoxic saponin from heat-processed Achyranthes fauriei roots[J].Biol Pharm Bull,2006,29(5):1053-1055.
[37]SONG X,WANG W,ZHANG X,et al.Deglucose chikusetsusaponinⅣa isolated from Rhizoma Panacis Majoris induces apoptosis in human Hep G2 hepatoma cells[J].Mol Med Rep,2015,12(4):5494-5500.
[38]RATTANATHONGKOM A,LEE JB,HAYASHI K,et al.Evaluation of chikusetsusaponinⅣa isolated from Alternanthera philoxeroides for its potency against viral replication[J].Planta Med,2009,75(8):829-835.
[39]HOSONO-NISHIYAMA K,MATSUMOTO T,KIYO-HARA H,et al.Suppression of fas-mediated optosis of keratinocyte cells by chikusetsu saponins isolated from the roots of Panax japonicus[J].Planta Med,2006,72(3):193-198.
[40]代艳文,袁丁,万静枝,等.竹节参总皂苷通过NF-κB通路对LPS致RAW264.7细胞炎症的保护作用研究[J].中国中药杂志,2014,39(11):2076-2080.
[41]贾银芝,杨中林.竹节参总皂苷对Triton WR-1339诱发的高脂血症小鼠降血脂作用研究[J].亚太传统医药,2015,11(12):9-11.
[42]杨莉,阮波,张长城,等.竹节参总皂苷通过JNK/Bcl-2/Bax信号通路对H2O2致SH-SY5Y神经细胞凋亡的保护作用研究[J].中药新药与临床药理,2016,27(5):627-631.
[43]向婷婷,张长城,刘朝奇,等.竹节参总皂苷干预自然衰老大鼠肝脏炎症的实验研究[J].中国药理学通报,2017,33(6):848-853.
[2]李成全,周健,徐洲,等.太白楤木的化学成分及药理作用研究进展[J].中南药学,2017,15(10):1401-1409.
[3]张小鸿,徐先祥.竹节参皂苷药理作用研究进展[J].天然产物研究与开发,2013(25):153-156、78.
[4]宋小妹,李林,杨光明,等.不同产地珠子参中竹节参皂苷Ⅳa含量测定[J].中国中药杂志,2010,35(7):885-887.
[5]范妤,郭东艳,宋强,等.太白楤木活性成分及其药理作用研究进展[J].现代中西医结合杂志,2014,23(2):221-223.
[6]LEE HJ,SHIN JS,LEE WS,et al.ChikusetsusaponinⅣa methyl ester isolated from the roots of Achyranthes japonica suppresses LPS-Induced i NOS,TNF-α,IL-6,and IL-1βexpression by NF-k B and AP-1 inactivation[J].Biol Pharm Bull,2016,39(5):657-664.
[7]南京中医药大学.中药大辞典[M].上海:上海科学技术出版社,2006:1-3875.
[8]许苗苗,张旋,宋蓓,等.珠子参抗肝损伤药效的物质基础研究[J].西北药学杂志,2014,29(5):486-489.
[9]杜原瑗,陈骞虎,贾绍辉,等.牛膝竹节参皂苷与杜仲松脂醇二葡萄糖苷联合治疗骨质疏松性骨折的实验研究[J].中国中医骨伤科杂志,2015,23(6):9-13.
[10]WENG Y,YU L,CUI J,et al.Antihyperglycemic,hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis in experimental type 2 diabetic rats[J].J Ethnopharmcol,2014,152(3):553-560.
[11]魏娜,袁丁,徐媛青,等.竹节参总皂苷对大鼠心肌梗死的保护作用[J].中药药理与临床,2013,29(3):75-78.
[12]闫佳佳,伍晓晓,段佳林,等.楤木皂苷对大鼠心肌缺血/再灌注损伤的保护作用[J].现代生物医学进展,2015,15(15):2829-2832.
[13]CAO Y,GU C,ZHAO F,et al.Therapeutic effects of cyathula officinalis kuan and its active fraction on acute blood stasis rat model and identification constituents by HPLC-QTOF/MS/MS[J].Pharmacogn Mag,2017,13(52):693-701.
[14]HE H,XU J,XU Y,et al.Cardioprotective effects of saponins from Panax japonicus on acute myocardial ischemia against oxidative stress-triggered damage and cardiac cell death in rats[J].J Ethnopharmacol,2012,140(1):73-82.
[15]LI Y,ZHANG T,CUI J,et al.Chikusetsu saponinⅣa regulates glucose uptake and fatty acid oxidation;implications in antihyperglycemic and hypolipidemic effects[J].JPharm Pharmacol,2015,67(7):997-1007.
[16]CHEN X,WU QS,MENG FC,et al.ChikusetsusaponinⅣa methyl ester induces G1cell cycle arrest,triggers apoptosis and inhibits migration and invasion in ovarian cancer cells[J].Phytomedicine,2017.DOI:10.1016/j.phymed.2017.05.003.
[17]YANG J,QIAN S,CAI X,et al.ChikusetsusaponinⅣa butyl ester(CS-Ⅳa-Be):a novel IL6R antagonist,inhibits IL6/STAT3 signaling pathway and induces cancer cell apoptosis[J].Mol Cancer Ther,2016,15(6):1190-1200.
[18]GUSTAFSSON AB,GOTTLIEB RA.Mechanisms of apoptosis in the heart[J].J Clin Immunol,2003,23(6):447-459.
[19]WANG SH,SHIH YL,KO WC,et al.Cadmium-induced autophagy and apoptosis are mediated by a calcium signaling pathway[J].Cell Mol Life Sci,2008,65(22):3640-3652.
[20]DUAN J,YIN Y,WEI G,et al.Chikusetsu saponinⅣa confers cardioprotection via SIRT1/ERK1/2 and Homer1a pathway[J].Sci Rep,2015.DOI:10.1038/srep18123.
[21]孙桂波,徐惠波,温富春,等.去葡萄糖竹节参皂苷Ⅳa对缺氧复氧心肌细胞损伤的保护作用[J].中国药理学与毒理学杂志,2005,19(6):424-427.
[22]GUO J,LI L,WU YJ,et al.Inhibitory effects of Brazilin on the vascular smooth muscle cell proliferation and migration induced by PDGF-BB[J].Am J Chin Med,2013,41(6):1283-1296.
[23]杨冬梅,聂娟,孙四玉,等.竹节参皂苷Ⅳa甲酯对血管紧张素Ⅱ诱导的血管平滑肌细胞增殖影响及机制研究[J].中国临床药理学与治疗学,2016,21(8):873-877.
[24]薛慧,王卫东.竹节参在治疗心脑血管病方面的研究进展[J].医学理论与实践,2008,21(11):127-1280.
[25]孙桂波,徐惠波,温富春,等.去葡萄糖竹节参皂苷Ⅳa抗实验性心律失常作用[J].中国药理学与毒理学杂志,2006,20(5):377-381.
[26]孙桂波,徐惠波,温富春,等.去葡萄糖竹节参皂苷Ⅳa对心肌电生理特性的影响[J].中国药理学通报,2006,22(11):1407-1408.
[27]DUAN J,YIN Y,CUI J,et al.Chikusetsu SaponinⅣa ameliorates cerebral ischemia reperfusion injury in diabetic mice via adiponectin-mediated AMPK/GSK-3βpathway in vivo and in vitro[J].Mol Neurobiol,2016,53(1):728-743.
[28]FANG X,HAN Q,LI S,et al.Chikusetsu saponinⅣa attenuates isoflurane-induced neurotoxicity and cognitive deficits via SIRT1/ERK1/2 in developmental rats[J].Am JTransl Res,2017,9(9):4288-4299.
[29]CUI J,XI M,LI Y,et al.Insulinotropic effect of chikusetsu saponinⅣa in diabetic rats and pancreaticβ-cells[J].JEthnopharmacology,2015.DOI:10.1016/j.jep.2015.02.032.
[30]YUAN C,LIU C,WANG T,et al.Chikusetsu saponinⅣa ameliorates high fat diet-induced inflammation in adipose tissue of mice through inhibition of NLRP3 inflammasome activation and NF-κB signaling[J].Oncotarget,2017,8(19):31023-31040.
[31]潘茂兴,顿耀艳,陈静,等.竹节参皂苷Ⅳa对高脂饮食小鼠小肠干细胞及其微环境Wnt/β-catenin信号通路的影响[J].中药材,2017,40(6):1415-1419.
[32]WANG H,QI J,LI L,et al.Inhibitory effects of chikusetsusaponinⅣa on lipopolysaccharide-induced pro-inflammatory responses in THP-1 cells[J].Int J Immunopathol Pharmacol,2015,28(3):308-317.
[33]DAHMER T,BERGER M,BARLETTE AG,et al.Antithrombotic effect of chikusetsusaponinⅣa isolated from Ilex paraguariensis(Maté)[J].J Med Food,2012,15(12):1073-1080.
[34]ZHU W,TIAN F,LIU L,et al.Chikusetsu(CHI)triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species(ROS)production[J].Biomed Pharmacother,2017.DOI:10.1016/j.biopha.2017.03.050.
[35]LEE KM,YUN JH,LEE DH,et al.ChikusetsusaponinⅣa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation ofβ-catenin in HCT116 cells[J].Biochem Biophys Res Commun,2015,459(4):591-596.
[36]YOO HH,KWON SW,PARK JH.The cytotoxic saponin from heat-processed Achyranthes fauriei roots[J].Biol Pharm Bull,2006,29(5):1053-1055.
[37]SONG X,WANG W,ZHANG X,et al.Deglucose chikusetsusaponinⅣa isolated from Rhizoma Panacis Majoris induces apoptosis in human Hep G2 hepatoma cells[J].Mol Med Rep,2015,12(4):5494-5500.
[38]RATTANATHONGKOM A,LEE JB,HAYASHI K,et al.Evaluation of chikusetsusaponinⅣa isolated from Alternanthera philoxeroides for its potency against viral replication[J].Planta Med,2009,75(8):829-835.
[39]HOSONO-NISHIYAMA K,MATSUMOTO T,KIYO-HARA H,et al.Suppression of fas-mediated optosis of keratinocyte cells by chikusetsu saponins isolated from the roots of Panax japonicus[J].Planta Med,2006,72(3):193-198.
[40]代艳文,袁丁,万静枝,等.竹节参总皂苷通过NF-κB通路对LPS致RAW264.7细胞炎症的保护作用研究[J].中国中药杂志,2014,39(11):2076-2080.
[41]贾银芝,杨中林.竹节参总皂苷对Triton WR-1339诱发的高脂血症小鼠降血脂作用研究[J].亚太传统医药,2015,11(12):9-11.
[42]杨莉,阮波,张长城,等.竹节参总皂苷通过JNK/Bcl-2/Bax信号通路对H2O2致SH-SY5Y神经细胞凋亡的保护作用研究[J].中药新药与临床药理,2016,27(5):627-631.
[43]向婷婷,张长城,刘朝奇,等.竹节参总皂苷干预自然衰老大鼠肝脏炎症的实验研究[J].中国药理学通报,2017,33(6):848-853.