目的 阐释通拉嘎-5抗绝经后骨质疏松的药效物质基础和作用机制。方法 采用HPLC-Q-Exactive MS/MS技术分析通拉嘎-5的入血原型成分,并利用分子对接技术表征入血原型成分与雌激素受体ER的结合能,探讨通拉嘎-5抗绝经后骨质疏松的作用机制。结果 分析得到入血原型成分26个,主要包括生物碱类、酚酸类和挥发油类；其中,桂二萜醇、荜茇环碱、胡椒碱、二氢胡椒碱和1,3-苯并间二氧杂环戊烯-5-丙醛与ERα、ERβ结合能均≤-5 kcal.mol_-1^,鞣花酸、对羟基苯甲酸、二氢荜茇明宁碱、荜茇宁、胡椒油碱B、(2E,4E,12Z)-N-Isobutylocatadeca-2,4,12-trienamide与Erα结合能≤-5 kcal.mol_-1^。结论 通拉嘎-5中桂二萜醇、胡椒碱等11个入血原型成分可能作用于雌激素受体而发挥抗绝经后骨质疏松的作用,可为该方质量控制研究和临床合理应用提供参考。

Objective To elucidate the pharmacological basis and mechanism of action of Tonlaga-5 against postmenopausal osteoporosis. Methods Analysis of the blood entry prototype component of Tonglaga-5 by HPLC-Q-Exactive MS/MS technique and characterization of the binding energy of the blood entry prototype component to the estrogen receptor ER using molecular docking technique to investigate the mechanism of action of Tongalaga-5 against postmenopausal osteoporosis. Results Twenty-six prototypical chemical components in serum were obtained ,mainly alkaloids, phenolic acids and volatile oils; molecular docking of the relevant components showed that Cinnzeylanol, Pipernonaline, Piperine, Dihydropiperlonguminine and 1,3-Benzodioxole-5- propanal with ERα and ERβ binding energies ≤ -5 kcal?mol_^-1, ellagic acid, p-hydroxybenzoic acid, Dihydropiperlonguminine,Piperlonguminine,Piperolein B, (2E,4E,12Z)-N-Isobuty-locatadeca-2,4,12-trienamide with Erα binding energy ≤-5 kcal?mol_-1^. Conclusion Cinnzeylanol, piperine and other 11 blood-entry prototype components in TLG-5 can exert anti-postmenopausal osteoporosis effects by acting on estrogen receptors, which can provide reference for quality control research and rational clinical application of this formula.

国家自然科学(82160745)；内蒙古医科大学致远人才计划(ZY0120014)；内蒙古医科大学大学生创新创业训练计划(202210132056)