清络通痹精简方中雷公藤“异类相制”减毒机制的化学基础

Chemical Basis of Tripterygium wilfordii Compatibility for Detoxicity in Qingluo Tongbi Decoction Based on ‘Diversity Restriction’

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.