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基于谱效关系分析从丹参-红花药对中发现抗血管性痴呆的多成分组合

Discovering a Multi-Component Combination against Vascular Dementia from Danshen-Honghua Herbal Pair by Spectrum-Effect Relationship Analysis.

作者信息

Zhang Peilin, He Shiru, Wu Siqi, Li Yi, Wang Huiying, Yan Changyang, Yang Hua, Li Ping

机构信息

State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China.

出版信息

Pharmaceuticals (Basel). 2022 Aug 29;15(9):1073. doi: 10.3390/ph15091073.

DOI:10.3390/ph15091073
PMID:36145294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9505896/
Abstract

The Danshen-Honghua (DH) herbal pair exhibits a synergistic effect in protecting the cerebrovascular system from ischemia/reperfusion injury, but the therapeutic effect on vascular dementia (VaD) has not been clarified, and the main active ingredient group has not been clarified. In this work, the chemical constituents in DH herbal pair extract were characterized by UHPLC-QTOF MS, and a total of 72 compounds were identified. Moreover, the DH herbal pair alleviated phenylhydrazine (PHZ)-induced thrombosis and improved bisphenol F (BPF)- and ponatinib-induced brain injury in zebrafish. Furthermore, the spectrum-effect relationship between the fingerprint of the DH herbal pair and the antithrombotic and neuroprotective efficacy was analyzed, and 11 chemical components were screened out as the multi-component combination (MCC) against VaD. Among them, the two compounds with the highest content were salvianolic acid B (17.31 ± 0.20 mg/g) and hydroxysafflor yellow A (15.85 ± 0.19 mg/g). Finally, we combined these 11 candidate compounds as the MCC and found that it could improve thrombosis and neuronal injury in three zebrafish models and rat bilateral common carotid artery occlusion (BCCAO) model, which had similar efficacy compared to the DH herbal pair. This study provides research ideas for the treatment of VaD and the clinical application of the DH herbal pair.

摘要

丹参-红花药对在保护脑血管系统免受缺血/再灌注损伤方面具有协同作用，但对血管性痴呆（VaD）的治疗效果尚未明确，主要活性成分组也未明确。在本研究中，采用超高效液相色谱-四极杆飞行时间质谱（UHPLC-QTOF MS）对丹参-红花药对提取物中的化学成分进行了表征，共鉴定出72种化合物。此外，丹参-红花药对减轻了苯肼（PHZ）诱导的血栓形成，并改善了双酚F（BPF）和波纳替尼诱导的斑马鱼脑损伤。此外，分析了丹参-红花药对指纹图谱与抗血栓和神经保护功效之间的谱效关系，筛选出11种化学成分作为抗VaD的多成分组合（MCC）。其中，含量最高的两种化合物是丹酚酸B（17.31±0.20 mg/g）和羟基红花黄色素A（15.85±0.19 mg/g）。最后，将这11种候选化合物组合成MCC，发现其可以改善三种斑马鱼模型和大鼠双侧颈总动脉闭塞（BCCAO）模型中的血栓形成和神经元损伤，其疗效与丹参-红花药对相似。本研究为VaD的治疗及丹参-红花药对的临床应用提供了研究思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b5f/9505896/c1add071179d/pharmaceuticals-15-01073-g007.jpg
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