清络通痹精简方中雷公藤“异类相制”减毒机制的化学基础
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摘要
目的:通过测定清络通痹精简方、单味雷公藤、雷公藤配伍三七、雷公藤配伍地黄组合中雷公藤3种毒性成分雷公藤甲素、雷公藤红素、雷公藤内酯甲的溶出含量,从化学成分角度探索"异类相制"减毒的规律,为雷公藤的临床配伍减毒应用提供实验依据。方法:利用高度选择性和灵敏度的三重四级杆质谱(LC-MS/MS)同时对3种有效成分——雷公藤甲素、雷公藤红素和雷公藤内酯甲进行检测,比较单味雷公藤组、雷公藤配伍三七组、雷公藤配伍地黄组、清络通痹精简方组中3种有效成分的溶出变化。结果:雷公藤药材水提液中雷公藤甲素的含量最高,雷公藤内酯甲次之,雷公藤红素的含量最低。而当雷公藤药材用量相同的情况下,雷公藤中3种有效成分在不同配伍环境下的溶出趋势一致,溶出顺序为单味雷公藤组>雷公藤配伍地黄组>雷公藤配伍三七组>清络通痹精简方组。结论:在配伍组合中三七对雷公藤3种有效成分的溶出有显著地抑制作用,地黄的抑制作用较弱,而清络通痹精简方中雷公藤3种有效成分的溶出明显降低。该研究结果为雷公藤的临床"异类相制"配伍减毒理论提供了实验依据。
Objective: By measuring dissolution contents of three kinds of toxic components(triptolide,tripterine,and wilforlide) in simplified Qingluo Tongbi decoction, Tripterygium wilfordii(TW), TW +Notoginseng Radix et Rhizoma,as well as TW + Rehmanniae Radix,explore ‘Diversity Restriction'mechanism of detoxicity from the perspective of the chemical basis composition,and provide experimental basis for clinical compatibility application of TW for detoxicity effect. Method: Highly selective and sensitive triple quadrupole mass spectrometry(LC-MS/MS) were used at the same time to detect three active ingredients-triptolide,tripterine and wilforlide,and then their dissolution changes were compared between TW,TW + Notoginseng Radix et Rhizoma,TW + Rehmanniae Radix,as well as Simplified Qingluo Tongbi decoction. Result: In TW medicinal water extract,triptolide had the highest content,followed by wilforlide,and the content of tripterine was lowest.When the amount of medicine TW was same,the dissolution trend of the above three active ingredients was consistent under different compatibility environments,and the dissolution order was as follows: TW > TW +Rehmanniae Radix > TW + Notoginseng Radix et Rhizoma > Simplified Qingluo Tongbi decoction. Conclusion: In the compatibility,Notoginseng Radix et Rhizoma had a significant inhibitory effect on dissolution of three active ingredients of TW,while Rehmanniae Radix had a weak inhibitory effect. In addition,the dissolution of three active ingredients was significantly reduced in Simplified Qingluo Tongbi decoction. The results provided an experimental basis for clinical ‘Diversity Restriction'detoxicity mechanism of TW.
Objective: By measuring dissolution contents of three kinds of toxic components(triptolide,tripterine,and wilforlide) in simplified Qingluo Tongbi decoction, Tripterygium wilfordii(TW), TW +Notoginseng Radix et Rhizoma,as well as TW + Rehmanniae Radix,explore ‘Diversity Restriction'mechanism of detoxicity from the perspective of the chemical basis composition,and provide experimental basis for clinical compatibility application of TW for detoxicity effect. Method: Highly selective and sensitive triple quadrupole mass spectrometry(LC-MS/MS) were used at the same time to detect three active ingredients-triptolide,tripterine and wilforlide,and then their dissolution changes were compared between TW,TW + Notoginseng Radix et Rhizoma,TW + Rehmanniae Radix,as well as Simplified Qingluo Tongbi decoction. Result: In TW medicinal water extract,triptolide had the highest content,followed by wilforlide,and the content of tripterine was lowest.When the amount of medicine TW was same,the dissolution trend of the above three active ingredients was consistent under different compatibility environments,and the dissolution order was as follows: TW > TW +Rehmanniae Radix > TW + Notoginseng Radix et Rhizoma > Simplified Qingluo Tongbi decoction. Conclusion: In the compatibility,Notoginseng Radix et Rhizoma had a significant inhibitory effect on dissolution of three active ingredients of TW,while Rehmanniae Radix had a weak inhibitory effect. In addition,the dissolution of three active ingredients was significantly reduced in Simplified Qingluo Tongbi decoction. The results provided an experimental basis for clinical ‘Diversity Restriction'detoxicity mechanism of TW.
引文
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[11]饶毅,魏惠珍,陈银芳,等.中药配伍应用于雷公藤减毒增效的研究进展[J].中国中药杂志,2008,33(14):1658-1661.
[12]杜倩,汤道权,陈永刚,等.配伍对生化汤中阿魏酸溶出的影响[J].时珍国医国药,2010,21(3):617-619.
[13]闰广利,王喜军,吕海涛.茵陈蒿汤不同配伍情况下主要有效成分的溶出率研究[J].中医药信息,2008,25(3):29-31.
[14]彭金咏,栾连军,程翼宇.精制血府逐瘀方不同配伍情况下芍药苷的溶出量[J].中国中药杂志,2003,28(6):516-518.
[15]陈建真,吕圭源,罗小敏,等.黄芩汤不同配伍对芍药苷溶出率的影响[J].中医药学报,2008,36(2):26-28.
[16]施栋磊.清络通痹复方配伍对有毒中药雷公藤的减毒作用机制研究[D].南京:南京中医药大学,2010.
[17]刘陶世,郭立玮,周学平,等.陶瓷膜微滤与树脂吸附等6种技术精制清络通痹水提液的对比研究[J].中成药,2004,6(4):266-269.
[18]刘蒙竹,张新龙,朱华旭,等.清络通痹方中雷公藤配伍减毒的化学基础研究[J].中国实验方剂学杂志,2014,20(7):107-112.
[19]马鑫斌,巴文强,王玎,等.雷公藤药材中雷公藤甲素及总二萜内酯的含量测定[J].中国中医药现代远程教育,2014,12(6):153-155.
[20]张贺,江莹,孟楣,等.HPLC法测定不同产地雷公藤药材中雷公藤内酯甲的含量[J].中国药房,2014,25(31):2916-2918.
[2]谢彤,周学平,林丽丽,等.基于“异类相制”的雷公藤复方配伍减毒代谢组学研究[J].中国中药杂志,2016,41(6):1124-1129.
[3]马哲,梁茂新,张颖.中药雷公藤化学成分及药理作用研究进展[J].亚太传统医药,2011,7(3):157-159.
[4]郭艳红,谭垦.雷公藤的毒性及其研究概况[J].中药材,2007,30(1):112-117.
[5]黄之镨,陈普,马伟光.雷公藤的毒性作用及减毒研究进展[J].中国民间民族医药,2013,22(12):20-21.
[6]马伟光,张滔,张超,等.有毒药物雷公藤的研究及展望[J].中华中医药杂志,2006,21(2):117-120.
[7]吴立军.天然药物化学[M].5版.北京:人民卫生出版社,2009:239-243.
[8]施栋磊,朱华旭,潘林梅,等.中药配伍雷公藤减毒作用的研究进展[J].中国药事,2009,23(11):1136-1140.
[9]高丽,聂中标,周然.雷公藤配伍中药减毒的实验研究进展[J].世界中西医结合杂志,2010,5(6):537-539.
[10]李春庆,孙伟,邵家德,等.雷公藤减毒研究评述[J].中国实验方剂学杂志,2011,17(10):263-264.
[11]饶毅,魏惠珍,陈银芳,等.中药配伍应用于雷公藤减毒增效的研究进展[J].中国中药杂志,2008,33(14):1658-1661.
[12]杜倩,汤道权,陈永刚,等.配伍对生化汤中阿魏酸溶出的影响[J].时珍国医国药,2010,21(3):617-619.
[13]闰广利,王喜军,吕海涛.茵陈蒿汤不同配伍情况下主要有效成分的溶出率研究[J].中医药信息,2008,25(3):29-31.
[14]彭金咏,栾连军,程翼宇.精制血府逐瘀方不同配伍情况下芍药苷的溶出量[J].中国中药杂志,2003,28(6):516-518.
[15]陈建真,吕圭源,罗小敏,等.黄芩汤不同配伍对芍药苷溶出率的影响[J].中医药学报,2008,36(2):26-28.
[16]施栋磊.清络通痹复方配伍对有毒中药雷公藤的减毒作用机制研究[D].南京:南京中医药大学,2010.
[17]刘陶世,郭立玮,周学平,等.陶瓷膜微滤与树脂吸附等6种技术精制清络通痹水提液的对比研究[J].中成药,2004,6(4):266-269.
[18]刘蒙竹,张新龙,朱华旭,等.清络通痹方中雷公藤配伍减毒的化学基础研究[J].中国实验方剂学杂志,2014,20(7):107-112.
[19]马鑫斌,巴文强,王玎,等.雷公藤药材中雷公藤甲素及总二萜内酯的含量测定[J].中国中医药现代远程教育,2014,12(6):153-155.
[20]张贺,江莹,孟楣,等.HPLC法测定不同产地雷公藤药材中雷公藤内酯甲的含量[J].中国药房,2014,25(31):2916-2918.