胡椒属植物抗血小板和抗血栓活性研究进展
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摘要
在我国,药用的胡椒属植物中,约1/3具有活血功能。研究发现,二十种胡椒属植物的提取物显示出抗血小板聚集活性。目前,从11种胡椒属植物中发现了抗血小板活性化合物51个,主要包括生物碱(占47%)、木脂素(占24%)、苯丙素(占22%)等。其中,海风藤酮、丁香酚、羟基胡椒酚乙酸酯等的抗血小板活性较为显著,pellitorine、荜茇酰胺、荜茇宁和丁香酚等表现出了体内抗凝及抗血栓活性。有必要在胡椒属化学成分抗血栓作用机制及抗血栓新靶点的活性筛选上,进行更深入的研究。
Among medicinal Piper plants used as traditional Chinese medicines,there are about 1 /3 species with the function of promoting blood circulation( Huoxue in Chinese). Crude extracts from 20 Piper plants are active against platelet aggregation. Fifty-one antiplatelet compounds,including alkaloids( 47%),lignans( 24%),phenylpropanoids( 22%),etc,have been isolated from the genus. Kadsurenone,eugenol and hydroxychavicol acetate showed significantly antiplatelet activity in vitro. Moreover,pellitorine,piperlongumine,piperlonguminine and eugenol possessed anticoagulant and antithrombotic effects in vivo. Further study on antithrombotic mechanisms and activity screening in new antithrombotic targets of Piper constituents is warranted.
Among medicinal Piper plants used as traditional Chinese medicines,there are about 1 /3 species with the function of promoting blood circulation( Huoxue in Chinese). Crude extracts from 20 Piper plants are active against platelet aggregation. Fifty-one antiplatelet compounds,including alkaloids( 47%),lignans( 24%),phenylpropanoids( 22%),etc,have been isolated from the genus. Kadsurenone,eugenol and hydroxychavicol acetate showed significantly antiplatelet activity in vitro. Moreover,pellitorine,piperlongumine,piperlonguminine and eugenol possessed anticoagulant and antithrombotic effects in vivo. Further study on antithrombotic mechanisms and activity screening in new antithrombotic targets of Piper constituents is warranted.
引文
1 Wang HR,et al.Comparison of therapeutic effect of recombinant tissue plasminogen activator by treatment time after onset of acute ischemic stroke.Sci Rep,2015,5:11743.
2 Xing JH(邢峻豪),et al.Advances in antithrombotic drugs.Prog Pharm Sci(药学进展),2014,38:174-184.
3 Huang ZS,et al.Salvianolic acid A inhibits platelet activation and arterial thrombosis via inhibition of phosphoinositide 3-kinase.J Thromb Haemost,2010,8:1383-1393.
4 Liu L,et al.Salvianolic acid B inhibits platelets as a P2Y(12)antagonist and PDE inhibitor:Evidence from clinic to laboratory.Thromb Res,2014,134:866-876.
5 Sun FZ(孙凤志),et al.Advances in Huoxue and Zhixue effects of Panax notoginseng,a traditional Chinese medicine.J Med Res(医学研究杂志),2013,42:24-26.
6 Xiang QL(向秋玲),et al.Protective effect of panaxatriol saponins on cerebral ischemia.J Sun Yat Sen Univ(Med Sci)(中山大学学报:医学科学版),2008,29:705-709.
7 Chen JW(陈健文),et al.Promoting blood circulation by removing blood stasis of panaxatriol saponins.Trad Chin Med Pharmacol Clin(中药药理与临床),2008,24:38-41.
8 Lau AJ,et al.Antiplatelet and anticoagulant effects of Panax notoginseng:comparison of raw and steamed Panax notoginseng with Panax ginseng and Panax quinquefolium.J Ethnopharmacol,2009,125:380-386.
9 Hao HZ,et al.Antiplatelet activity of loureirin A by attenuating Akt phosphorylation:in vitro studies.Eur J Pharmacol,2015,746:63-69.
10 Xin N,et al.Dragon's Blood extract has antithrombotic properties,affecting platelet aggregation functions and anticoagulation activities.J Ethnopharmacol,2011,135:510-514.
11 Tseng YC,et al.Piperaceae.In:Wu,ZY,Raven PH,Hong,D.Y.editors.Flora of China.Beijing/St.Louis:Science Press/Missouri Botanical Garden Press,1999.Vol 4,110-129.
12 Wang YH,et al.Anticancer principles from medicinal Piper plants.J Tradit Complement Med,2014,4:8-16.
13 Editorial Board of'Zhonghua Bencao',State Administration of Traditional Chinese Medicine of the People's Republic of China(国家中医药管理局《中华本草》编委会).Zhonghua Bencao(中华本草).Shanghai:Shanghai Scientific and Technological Press,1999.Vol 3,424-449.
14 Wu ZY(吴征镒),et al.Xinhua Bencao Gangyao(新华本草纲要).Shanghai:Shanghai Scientific and Technological Press,1988.Vol 1,190-196.
15 Li CL(李长龄),et al.Anti-PAF effects of about 100 traditional Chinese medicines.Physiol Sci(生理科学),1987,7:316-316.
16 Li CL(李长龄),et al.Anti-PAF effects of more than 100traditional Chinese medicines.Chin Pharmacol Bull(中国药理学通报),1987,3:298-298.
17 Li CL(李长龄),et al.Anti-PAF effects of alcohol extracts from Piper hancei.Physiol Sci(生理科学),1987,7:316-317.
18 Chen S,et al.Neolignans and phenylpropanoids from the roots of Piper taiwanense and their antiplatelet and antitubercular activities.Phytochemistry,2013,93:203-209.
19 Guerrini A,et al.Bioactivities of Piper aduncum L.and Piper obliquum Ruiz&Pavon(Piperaceae)essential oils from eastern Ecuador.Environ.Toxicol Pharmacol,2009,27:39-48.
20 Shen ZQ(沈志强),et al.PAF-antagonist screening from 12alcohol extracts of Piper species native to Yunnan.Acad J Kunming Med Coll(昆明医学院学报),1997,18:23-25.
21 Shen ZQ(沈志强),et al.Study on antiplatelet activity of alcohol extracts from Piper species native to Yunnan.Nat Prod Res Dev(天然产物研究与开发),1999,11:27-31.
22 Lei D,et al.Antioxidative and antiplatelet effects of aqueous inflorescence Piper betle extract.J Agric Food Chem,2003,51:2083-2088.
23 Zhao SF(赵淑芬),et al.The inhibitory effect of alcoholic extracts of Piper hancei on platelet aggregation.J Cap Univ Med Sci(首都医学院学报),1996,17:28-31.
24 Chen IS,et al.Amides with anti-platelet aggregation activity from Piper taiwanense.Fitoterapia,2007,78:414-419.
25 Shen YZ,et al.Characterization of a platelet-activating factor receptor antagonist,kadsurenone:specific inhibition of platelet-activating factor in vitro and in vivo.J Chin Pharm Sci,1994,3:59-64.
26 Raghavendra R,et al.Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis.Prostag Leukot Essent Fatty Acids,2009,81:73-78.
27 Tognolini M,et al.Comparative screening of plant essential oils:phenylpropanoid moiety as basic core for antiplatelet activity.Life Sci,2006,78:1419-1432.
28 Lee W,et al.Anticoagulant activities of piperlonguminine in vitro and in vivo.BMP Rep,2013,46:484-489.
29 Tsai IL,et al.New cytotoxic cyclobutanoid amides,a new furanoid lignan and anti-platelet aggregation constituents from Piper arborescens.Planta Med,2005,71:535-542.
30 Li CY,et al.Isolation and identification of antiplatelet aggregatory principles from the leaves of Piper lolot.J Agric Food Chem,2007,55:9436-9442.
31 Chen YC,et al.Lignans,an amide and anti-platelet activities from Piper philippinum.Phytochemistry,2007,68:2101-2111.
32 Park BS,et al.Antiplatelet effects of acidamides isolated from the fruits of Piper longum L.Phytomedicine,2007,14:853-855.
33 Fontenele JB,et al.Antiplatelet effects of piplartine,an alkamide isolated from Piper tuberculatum:possible involvement of cyclooxygenase blockade and antioxidant activity.J Pharm Pharmacol,2009,61:511-515.
34 Son DJ,et al.Piperine inhibits the activities of platelet cytosolic phospholipase A2 and thromboxane A2 synthase without affecting cyclooxygenase-1 activity:different mechanisms of action are involved in the inhibition of platelet aggregation and macrophage inflammatory response.Nutrients,2014,6:3336-3352.
35 Chen YC,et al.A new aristolactam alkaloid and anti-platelet aggregation constituents from Piper taiwanense.Planta Med,2004,70:174-177.
36 Teng CM,et al.Comparison of the actions of some plateletactivating factor antagonists on platelets and aortic smooth muscles.Eur J Pharmacol,1991,205:151-156.
37 Ammit AJ,et al.Platelet-activating factor(PAF)receptor antagonists inhibit arachidonic acid induced platelet aggregation in rabbit whole blood.Lipids,1991,26:1189-1192.
38 Han GQ(韩桂秋),et al.The isolation and identification of PAF receptor antagonist from Piper wallichii(Miq)HandMazz.J Beijing Med Univ(北京医科大学学报),1987,19:243-245.
39 Shi YN,et al.Lignans and aromatic glycosides from Piper wallichii and their antithrombotic activities.J Ethnopharmacol,2015,162:87-96.
40 Chen S,et al.Three new phenylpropanoids from the roots of Piper taiwanense and their inhibitory activities on platelet aggregation and Mycobacterium tuberculosis.Chem Biodivers,2014,11:792-799.
41 Gleitz J,et al.Antithrombotic action of the kava pyrone(+)-kavain prepared from Piper methysticum on human platelets.Planta Med,1997,63:27-30.
42 Saeed SA,et al.Triterpenes andβ-sitosterol from Piper betle:isolation,antiplatelet and anti-inflammatory effects.Biochem Soc Trans,1993,21:462S-462S.
43 Yang J(杨嘉),et al.Chinese herbal medicine research of antithrombotic effect.Nat Prod Res Dev(天然产物研究与开发),1997,9:17-20.
44 Ku SK,et al.Antithrombotic activities of pellitorine in vitro and in vivo.Fitoterapia,2013,91:1-8.
45 Lee SE,et al.Proteomic evaluation on antiplatelet activity of piperlongumine derived from Piper longum.Mol Cell Toxicol,2010,6:295-303.
46 Mnafgui K,et al.Anti-inflammatory,antithrombotic and cardiac remodeling preventive effects of eugenol in isoproterenol-induced myocardial infarction in Wistar rat.Cardiovasc Toxicol,2015,Accepted.
47 Iwashita M,et al.Piperlongumine,a constituent of Piper longum L.,inhibits rabbit platelet aggregation as a thromboxane A 2 receptor antagonist.Eur J Pharmacol,2007,570:38-42.
48 Coy ED,et al.COX,LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.Bioorg Med Chem Lett,2009,19:6922-6925.
49 Chang M,et al.Hydroxychavicol,a novel betel leaf component,inhibits platelet aggregation by suppression of cyclooxygenase,thromboxane production and calcium mobilization.Br J Pharmacol,2007,152:73-82.
50 He ZY(何作云),et al.A preliminary study on the treatment of coronary heart disease with total flavone of Caulis Piperis Futokadsurae.Chin J Integr Tradit West Med(中西医结合杂志),1983,3:271-271.
51 Zhang JM(张基谟),et al.The treatment of 87 cases with cerebral infarction using total flavone of Caulis Piperis Futokadsurae and animal experiments.J Apoplexy Nerv Dis(中风与神经疾病杂志),1987,4:180-182.
52 Jiang M(姜明).The clinical application of 38 cases with cerebral thrombosis using self-made modified Siteng decoction.Mod Med Health(现代医药卫生),2010,26:1708-1709.
53 Yu HW(禹华玮),et al.Coagulation factorⅪ,a new target for antithrombotic therapy.Prac J Med Pharm(实用医药杂志),2014,31:170-172.
54 He ZL(何志龙),et al.Research advances in antithrombotic new target of PI3K.Pharm Biotechnol(药物生物技术),2014,21:373-376.
2 Xing JH(邢峻豪),et al.Advances in antithrombotic drugs.Prog Pharm Sci(药学进展),2014,38:174-184.
3 Huang ZS,et al.Salvianolic acid A inhibits platelet activation and arterial thrombosis via inhibition of phosphoinositide 3-kinase.J Thromb Haemost,2010,8:1383-1393.
4 Liu L,et al.Salvianolic acid B inhibits platelets as a P2Y(12)antagonist and PDE inhibitor:Evidence from clinic to laboratory.Thromb Res,2014,134:866-876.
5 Sun FZ(孙凤志),et al.Advances in Huoxue and Zhixue effects of Panax notoginseng,a traditional Chinese medicine.J Med Res(医学研究杂志),2013,42:24-26.
6 Xiang QL(向秋玲),et al.Protective effect of panaxatriol saponins on cerebral ischemia.J Sun Yat Sen Univ(Med Sci)(中山大学学报:医学科学版),2008,29:705-709.
7 Chen JW(陈健文),et al.Promoting blood circulation by removing blood stasis of panaxatriol saponins.Trad Chin Med Pharmacol Clin(中药药理与临床),2008,24:38-41.
8 Lau AJ,et al.Antiplatelet and anticoagulant effects of Panax notoginseng:comparison of raw and steamed Panax notoginseng with Panax ginseng and Panax quinquefolium.J Ethnopharmacol,2009,125:380-386.
9 Hao HZ,et al.Antiplatelet activity of loureirin A by attenuating Akt phosphorylation:in vitro studies.Eur J Pharmacol,2015,746:63-69.
10 Xin N,et al.Dragon's Blood extract has antithrombotic properties,affecting platelet aggregation functions and anticoagulation activities.J Ethnopharmacol,2011,135:510-514.
11 Tseng YC,et al.Piperaceae.In:Wu,ZY,Raven PH,Hong,D.Y.editors.Flora of China.Beijing/St.Louis:Science Press/Missouri Botanical Garden Press,1999.Vol 4,110-129.
12 Wang YH,et al.Anticancer principles from medicinal Piper plants.J Tradit Complement Med,2014,4:8-16.
13 Editorial Board of'Zhonghua Bencao',State Administration of Traditional Chinese Medicine of the People's Republic of China(国家中医药管理局《中华本草》编委会).Zhonghua Bencao(中华本草).Shanghai:Shanghai Scientific and Technological Press,1999.Vol 3,424-449.
14 Wu ZY(吴征镒),et al.Xinhua Bencao Gangyao(新华本草纲要).Shanghai:Shanghai Scientific and Technological Press,1988.Vol 1,190-196.
15 Li CL(李长龄),et al.Anti-PAF effects of about 100 traditional Chinese medicines.Physiol Sci(生理科学),1987,7:316-316.
16 Li CL(李长龄),et al.Anti-PAF effects of more than 100traditional Chinese medicines.Chin Pharmacol Bull(中国药理学通报),1987,3:298-298.
17 Li CL(李长龄),et al.Anti-PAF effects of alcohol extracts from Piper hancei.Physiol Sci(生理科学),1987,7:316-317.
18 Chen S,et al.Neolignans and phenylpropanoids from the roots of Piper taiwanense and their antiplatelet and antitubercular activities.Phytochemistry,2013,93:203-209.
19 Guerrini A,et al.Bioactivities of Piper aduncum L.and Piper obliquum Ruiz&Pavon(Piperaceae)essential oils from eastern Ecuador.Environ.Toxicol Pharmacol,2009,27:39-48.
20 Shen ZQ(沈志强),et al.PAF-antagonist screening from 12alcohol extracts of Piper species native to Yunnan.Acad J Kunming Med Coll(昆明医学院学报),1997,18:23-25.
21 Shen ZQ(沈志强),et al.Study on antiplatelet activity of alcohol extracts from Piper species native to Yunnan.Nat Prod Res Dev(天然产物研究与开发),1999,11:27-31.
22 Lei D,et al.Antioxidative and antiplatelet effects of aqueous inflorescence Piper betle extract.J Agric Food Chem,2003,51:2083-2088.
23 Zhao SF(赵淑芬),et al.The inhibitory effect of alcoholic extracts of Piper hancei on platelet aggregation.J Cap Univ Med Sci(首都医学院学报),1996,17:28-31.
24 Chen IS,et al.Amides with anti-platelet aggregation activity from Piper taiwanense.Fitoterapia,2007,78:414-419.
25 Shen YZ,et al.Characterization of a platelet-activating factor receptor antagonist,kadsurenone:specific inhibition of platelet-activating factor in vitro and in vivo.J Chin Pharm Sci,1994,3:59-64.
26 Raghavendra R,et al.Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis.Prostag Leukot Essent Fatty Acids,2009,81:73-78.
27 Tognolini M,et al.Comparative screening of plant essential oils:phenylpropanoid moiety as basic core for antiplatelet activity.Life Sci,2006,78:1419-1432.
28 Lee W,et al.Anticoagulant activities of piperlonguminine in vitro and in vivo.BMP Rep,2013,46:484-489.
29 Tsai IL,et al.New cytotoxic cyclobutanoid amides,a new furanoid lignan and anti-platelet aggregation constituents from Piper arborescens.Planta Med,2005,71:535-542.
30 Li CY,et al.Isolation and identification of antiplatelet aggregatory principles from the leaves of Piper lolot.J Agric Food Chem,2007,55:9436-9442.
31 Chen YC,et al.Lignans,an amide and anti-platelet activities from Piper philippinum.Phytochemistry,2007,68:2101-2111.
32 Park BS,et al.Antiplatelet effects of acidamides isolated from the fruits of Piper longum L.Phytomedicine,2007,14:853-855.
33 Fontenele JB,et al.Antiplatelet effects of piplartine,an alkamide isolated from Piper tuberculatum:possible involvement of cyclooxygenase blockade and antioxidant activity.J Pharm Pharmacol,2009,61:511-515.
34 Son DJ,et al.Piperine inhibits the activities of platelet cytosolic phospholipase A2 and thromboxane A2 synthase without affecting cyclooxygenase-1 activity:different mechanisms of action are involved in the inhibition of platelet aggregation and macrophage inflammatory response.Nutrients,2014,6:3336-3352.
35 Chen YC,et al.A new aristolactam alkaloid and anti-platelet aggregation constituents from Piper taiwanense.Planta Med,2004,70:174-177.
36 Teng CM,et al.Comparison of the actions of some plateletactivating factor antagonists on platelets and aortic smooth muscles.Eur J Pharmacol,1991,205:151-156.
37 Ammit AJ,et al.Platelet-activating factor(PAF)receptor antagonists inhibit arachidonic acid induced platelet aggregation in rabbit whole blood.Lipids,1991,26:1189-1192.
38 Han GQ(韩桂秋),et al.The isolation and identification of PAF receptor antagonist from Piper wallichii(Miq)HandMazz.J Beijing Med Univ(北京医科大学学报),1987,19:243-245.
39 Shi YN,et al.Lignans and aromatic glycosides from Piper wallichii and their antithrombotic activities.J Ethnopharmacol,2015,162:87-96.
40 Chen S,et al.Three new phenylpropanoids from the roots of Piper taiwanense and their inhibitory activities on platelet aggregation and Mycobacterium tuberculosis.Chem Biodivers,2014,11:792-799.
41 Gleitz J,et al.Antithrombotic action of the kava pyrone(+)-kavain prepared from Piper methysticum on human platelets.Planta Med,1997,63:27-30.
42 Saeed SA,et al.Triterpenes andβ-sitosterol from Piper betle:isolation,antiplatelet and anti-inflammatory effects.Biochem Soc Trans,1993,21:462S-462S.
43 Yang J(杨嘉),et al.Chinese herbal medicine research of antithrombotic effect.Nat Prod Res Dev(天然产物研究与开发),1997,9:17-20.
44 Ku SK,et al.Antithrombotic activities of pellitorine in vitro and in vivo.Fitoterapia,2013,91:1-8.
45 Lee SE,et al.Proteomic evaluation on antiplatelet activity of piperlongumine derived from Piper longum.Mol Cell Toxicol,2010,6:295-303.
46 Mnafgui K,et al.Anti-inflammatory,antithrombotic and cardiac remodeling preventive effects of eugenol in isoproterenol-induced myocardial infarction in Wistar rat.Cardiovasc Toxicol,2015,Accepted.
47 Iwashita M,et al.Piperlongumine,a constituent of Piper longum L.,inhibits rabbit platelet aggregation as a thromboxane A 2 receptor antagonist.Eur J Pharmacol,2007,570:38-42.
48 Coy ED,et al.COX,LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.Bioorg Med Chem Lett,2009,19:6922-6925.
49 Chang M,et al.Hydroxychavicol,a novel betel leaf component,inhibits platelet aggregation by suppression of cyclooxygenase,thromboxane production and calcium mobilization.Br J Pharmacol,2007,152:73-82.
50 He ZY(何作云),et al.A preliminary study on the treatment of coronary heart disease with total flavone of Caulis Piperis Futokadsurae.Chin J Integr Tradit West Med(中西医结合杂志),1983,3:271-271.
51 Zhang JM(张基谟),et al.The treatment of 87 cases with cerebral infarction using total flavone of Caulis Piperis Futokadsurae and animal experiments.J Apoplexy Nerv Dis(中风与神经疾病杂志),1987,4:180-182.
52 Jiang M(姜明).The clinical application of 38 cases with cerebral thrombosis using self-made modified Siteng decoction.Mod Med Health(现代医药卫生),2010,26:1708-1709.
53 Yu HW(禹华玮),et al.Coagulation factorⅪ,a new target for antithrombotic therapy.Prac J Med Pharm(实用医药杂志),2014,31:170-172.
54 He ZL(何志龙),et al.Research advances in antithrombotic new target of PI3K.Pharm Biotechnol(药物生物技术),2014,21:373-376.