中国人民解放军总医院Yong-ming Yao等研究人员合作发现，中草药静脉注射制剂血必净中具有抗败血症作用的重要药理成分。这一研究成果于2024年1月24日在线发表在国际学术期刊《中国药理学报》上。

研究人员确定了血必净抗败血症作用的综合活性成分。通过盲肠结扎术（CLP）诱导大鼠发生败血症。在给大鼠静脉注射一定剂量的血必净后，研究人员根据大鼠的全身暴露水平和抗败血病活性，对这些化合物进行了鉴定。此外，通过与血必净进行比较，对已确定的复方制剂的主要治疗效果、药动学等效性和药动学兼容性进行了评估。结果表明，在接受了血必净治疗的中毒性大鼠体内，共有12种血必净化合物在未改变或代谢的情况下进行了循环，并产生了显著的全身暴露。

在这些化合物中，羟基红花黄色素 A、芍药苷、氧化芍药苷、芍药内酯苷、川芎内酯I和丹参素具有显著的抗败血症活性，包括调节免疫反应、抑制过度炎症、调节止血和改善器官功能。六种化合物的复方制剂在中毒性大鼠体内的存活率和全身暴露量与血必净相似，其剂量与血必净相同。在六种活性化合物之间的相互作用以及其他循环中的血必净化合物的影响方面，复方和血必净均显示出高度的药代动力学兼容性。血必净药理成分的鉴定支持了该药的抗败血症用途，并为基于多药理学方法开发有效治疗败血症的药物提供了启示。

据介绍，败血症是一种危及生命的健康问题，但却缺乏针对败血症反应的有效药物。在中国，静脉注射中药血必净与常规治疗相结合，通过调节败血症反应降低了重症患者28天的死亡率。

附：英文原文

Title: Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation

Author: Cheng, Chen, Ren, Chao, Li, Mu-zi, Liu, Yi-hui, Yao, Ren-qi, Yu, Yang, Yu, Xuan, Wang, Jian-li, Wang, Li-xue, Leng, Yu-chun, Zhang, Hui, Du, Fei-fei, Dong, Ning, Wang, Feng-qing, Wu, Yao, Xu, Fang, Zhu, Xiao-mei, Zhang, Gui-ping, Dong, Kai, Liu, Si, Yao, Xiao-qing, Li, Chuan, Yao, Yong-ming

Issue&Volume: 2024-01-24

Abstract: Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing’s anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing’s pharmacologically significant constituents supports the medicine’s anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

DOI: 10.1038/s41401-023-01224-1

Source: https://www.nature.com/articles/s41401-023-01224-1