双黄连注射液指标性成分致类过敏反应评价

doi:10.19803/j.1672-8629.20250899

摘要/Abstract

摘要： 目的采用体外细胞脱颗粒实验方法并结合分子对接技术,对双黄连注射液及其指标性成分进行类过敏反应评价。方法使用高效液相色谱法对双黄连注射液中含有的指标性成分进行表征,以MrgprX2受体为目标蛋白,利用AutoDock Vina和PyMOL软件与双黄连注射液中含有的4种指标性成分（绿原酸、咖啡酸、黄芩苷、连翘苷）为配体进行分子对接,初步筛选可能致类过敏的活性成分,并利用RBL-2H3和P815细胞构建体外类过敏检测模型,分别使用最大无毒剂量的双黄连注射液及4、2、1、0.5倍剂量的绿原酸、咖啡酸、黄芩苷、连翘苷4种指标性成分（绿原酸、咖啡酸、黄芩苷、连翘苷1倍剂量指标性成分含量分别为0.097、0.032、0.25、0.07 mg·mL^-1）,通过检测细胞上清中组胺和β-氨基己糖苷酶含量,进一步判断双黄连注射液潜在过敏成分的致敏性。结果建立的基于MrgprX2受体的筛选模型可对药物潜在类过敏成分进行初步筛选,高效液相结果显示双黄连注射液中含有绿原酸、咖啡酸、黄芩苷和连翘苷4种指标性成分,分子对接筛选出的双黄连注射液中主成分黄芩苷与MrgprX2受体具有较高的亲和力,提示绿原酸、咖啡酸、黄芩苷、连翘苷具有潜在致类过敏的风险,使用RBL-2H3和P815细胞进行的体外类过敏活性检测,显示绿原酸、咖啡酸、黄芩苷具有较高致类过敏风险。结论双黄连注射液致类过敏可能是其含有的指标性成分间相互作用的结果。

关键词: 双黄连注射液, 中药注射液, 类过敏反应, G蛋白偶联受体X2(MrgprX2), RBL-2H3细胞, P815细胞, 分子对接

Abstract: Objective To evaluate the pseudo-allergic reactions of Shuanghuanglian injection and its indicator components using an in vitro cell degranulation assay combined with molecular docking. Methods The indicator components of Shuanghuanglian injection were characterized using high-performance liquid chromatography. With the MrgprX2 receptor as the target protein and with four characteristic monomeric components—chlorogenic acid, caffeic acid, baicalin, and forsythin—as ligands, molecular docking was performed using AutoDock Vina and PyMOL software to screen for potentially anaphylactoid-inducing active ingredients. In vitro anaphylactoid testing was conducted using RBL-2H3 and P815 cells. The maximum non-toxic dose of Shuanghuanglian injection and four indicator components (chlorogenic acid, caffeic acid, baicalin, and forsythin) at 4, 2, 1, and 0.5-fold doses were used respectively, where the ingredients of the four indicator components at 1-fold dose were 0.097 mg·mL⁻¹ for chlorogenic acid, 0.032 mg·mL⁻¹ for caffeic acid, 0.25 mg·mL⁻¹ for baicalin, and 0.07 mg·mL⁻¹ for forsythin. By measuring the levels of histamine and β-hexosaminidase in the cell supernatant, the sensitization potential of the potential allergenic components of Shuanghuanglian injection was evaluated. Results The screening model established based on the MrgprX2 receptor could be used for preliminary screening of potential anaphylactoid components of the drug HPLC results showed that Shuanghuanglian injection contained four indicator components: chlorogenic acid, caffeic acid, baicalin, and forsythin. Baicalin, the main component identified from Shuanghuanglian injection screened by molecular docking, had high affinity for the MrgprX2 receptor, suggesting that chlorogenic acid, caffeic acid, baicalin, and forsythin carried potential anaphylactoid risks. Subsequent in vitro anaphylactoid activity assays using RBL-2H3 and P815 cells indicated that chlorogenic acid, caffeic acid, and baicalin were likely to increase the risk of anaphylactoid reactions. Conclusion Anaphylactoid reactions induced by Shuanghuanglian injection may result from the interactions between its indicator components.

Key words: Shuanghuanglian Injection, Traditional Chinese Medicine Injection, Allergic Reactions, MrgprX2, RBL-2H3 cell, P815 cell, Molecular Docking

中图分类号:

R978
R994.11

吴彦霖, 于思思, 温苗, 李慧敏, 杨泽岸, 张媛, 贺庆. 双黄连注射液指标性成分致类过敏反应评价[J]. 中国药物警戒, 2026, 23(5): 539-546.

WU Yanlin, YU Sisi, WEN Miao, LI Huimin, YANG Zean, ZHANG Yuan, HE Qing. Evaluation of Allergic Reactions Caused by Indicator Components of Shuanghuanglian Injection[J]. Chinese Journal of Pharmacovigilance, 2026, 23(5): 539-546.

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https://zgywjj.magtechjournal.com/CN/Y2026/V23/I5/539

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