【摘要】 目的 基于中药复方中柚皮苷与单体柚皮苷热稳定性的差异，从核心功效成分的化学稳定性角度探讨中药复方配伍合理性。方法 采用网络药理学及分子对接技术预测柚皮苷治疗原发性骨质疏松症的核心靶点、关键信号通路及生物过程等生物信息，验证柚皮苷作为丹苓补骨胶囊核心功效成分和质量指标性成分的合理性；利用UPLC-Q-TOF/MS技术对丹苓补骨胶囊中的抗氧化活性成分进行定性分析，并基于密度泛函理论（DFT）及DPPH、ABTS、ORAC 3种体外抗氧化活性测定方法，预测分析各成分的抗氧化活性强弱及抗氧化作用机制，进而从核心功效成分化学稳定性的角度分析探讨复方配伍的合理性。结果 网络药理学与分子对接结果表明，柚皮苷治疗原发性骨质疏松症的潜在作用靶点为34个，其中有6个核心靶点，分别为ALB、TNF、ESR1、CASP3、SERPINE1、ACE，柚皮苷治疗原发性骨质疏松症涉及细胞周期、凋亡、信号传导等多种生物过程以及p53、IL-17、PI3K-Akt等多条信号通路；柚皮苷与核心靶点基因所编码的蛋白结合效果良好，结合能均小于-5 kJ·mol-1；通过UPLC-Q-TOF/MS技术确定了丹苓补骨胶囊中柚皮苷、淫羊藿苷、丹酚酸B、毛蕊异黄酮葡萄糖苷4种天然酚类抗氧化活性成分的存在；DFT计算和体外抗氧化活性实验结果表明，4种酚类化合物的抗氧化活性强弱顺序为：丹酚酸B>毛蕊异黄酮葡萄糖苷>淫羊藿苷和柚皮苷；稳定性验证实验结果表明，丹苓补骨胶囊中丹酚酸B等抗氧化活性成分对柚皮苷具有显著的保护作用，可显著提高复方中柚皮苷的热稳定性。结论 丹苓补骨胶囊中丹参等含有抗氧化活性成分的药味与君药骨碎补配伍时，丹酚酸B等抗氧化活性强于柚皮苷的成分在处方中可充当抗氧化剂，从而显著增强柚皮苷在生产和制剂贮藏过程中的化学稳定性，保证其在丹苓补骨胶囊中含量的稳定，有利于改善丹苓补骨胶囊的质量和临床疗效。进而从中药复方核心功效成分的化学稳定性角度证实了丹苓补骨胶囊中君药骨碎补与其他药味配伍的科学性和合理性。更多还原

【Abstract】 Objective To determine the compatibility of rationality in traditional Chinese medicine compound formulas from the chemical stability of naringin, a core active ingredient, based on the differences in thermal stability between compound formula and a single compound. Methods Network pharmacology and molecular docking were used to predict the core targets, key signaling pathways, biological processes, and other information of naringin in the treatment of primary osteoporosis(POP), to validate the rationality of naringin as the core active ingredient and quality indicator of Danling Bugu capsules. UPLC-Q-TOF/MS technology was utilized to qualitatively analyze antioxidant active components in Danling Bugu capsules. Based on density functional theory(DFT) and three in vitro antioxidation assays(DPPH, ABTS, and ORAC), the antioxidation and mechanism of each component were analyzed to determine the compatibility rationality of Danling Bugu capsules from the chemical stability of naringin. Results The network pharmacology and molecular docking indicated 34 potential targets of naringin in the treatment of POP, with 6 core targets being ALB, TNF, ESR1, CASP3, SERPINE1, and ACE. The treatment of POP with naringin involved multiple biological processes such as the cell cycle, apoptosis, and signal transduction, as well as several signaling pathways such as p53, IL-17, and PI3K-Akt. Naringin exhibited strong binding affinity with proteins encoded by core target genes, with binding energies all less than-5kJ·mol-1. With UPLC-Q-TOF/MS technology, four natural phenolic antioxidant active components were identified in Danling Bugu capsules: naringin, icariin, salvianolic acid B, and calycosin-7-O-glucoside. DFT calculations and in vitro antioxidation experiments demonstrated the order of antioxidation of the four phenolic compounds follows the order: salvianolic acid B > calycosin-7-Oglucoside > icariin and naringin. The stability verification experiments indicated that the antioxidation components, such as salvianolic acid B in Danling Bugu capsules, exhibited obvious significant protective effect on naringin, markedly enhancing its thermal stability within the compound.Conclusion When Danshen is combined with the monarch herb Drynariae Rhizoma, components like salvianolic acid B exhibit stronger antioxidant activity than naringin, and serve as antioxidants in the formulation. This greatly enhances the chemical stability of naringin during the production and storage of Danling Bugu capsules. The compatibility of the monarch herb Drynariae Rhizoma with other herbal medicines in traditional Chinese medicine formulations is rational.更多还原