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一种揭示养血清脑颗粒有效成分对脑缺血再灌注损伤的协同谱效关系的新方法。

A novel framework for uncovering the coordinative spectrum-effect correlation of the effective components of Yangyin Tongnao Granules on cerebral ischemia-reperfusion injury in rats.

机构信息

The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Zhejiang Chinese Medical University, Hangzhou, 310053, China.

School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118844. doi: 10.1016/j.jep.2024.118844. Epub 2024 Sep 19.

DOI:10.1016/j.jep.2024.118844
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ischemic stroke is currently a major public health hazard.Yangyin Tongnao Granules (YYTN), a traditional Chinese medicinal prescription, exerts potential therapeutic effects on subsequent cerebral ischemia-reperfusion injury (CIRI) after ischemic stroke. However, further studies are required to comprehend the underlying mechanism of YYTN for treating CIRI and the associated spectrum-effect mechanisms.

AIM OF THE STUDY

To investigate the coordinated correlation between the fingerprint and the pharmacodynamic indexes of the effective components (total flavonoids, total saponins, total alkaloids, and total phenolic acids) in YYTN for treating CIRI in rats.

METHODS

The fingerprints of five specific components (ligustrazine, puerarin, ferulic acid, calycosin, and formononetin) of YYTN in rats with middle cerebral artery occlusion (MCAO) were established using high-performance liquid chromatography (HPLC), and their peak areas were quantified in plasma samples. The pharmacodynamic indexes of tumor necrosis factor-alpha (TNF-α), cytochrome c (Cyt-C), and total superoxide dismutase (T-SOD) were integrated using the Criteria Importance Through Intercriteria Correlation (CRITIC) method to create a comprehensive evaluation index. Spectrum-effect correlation was analyzed by performing gray relation analysis (GRA), correlation analysis (CA), and partial least squares regression (PLSR). The Borda method was then applied to integrate the obtained results.

RESULTS

In MCAO rats, the effective components of YYTN reduced TNF-α and Cyt-C and increased T-SOD, which indicates their anti-inflammatory, antiapoptotic, and antioxidant effects. Spectrum-effect CA revealed certain associations between the chromatographic peaks of the five main components and the comprehensive pharmacodynamic evaluation index. Of these components, formononetin displayed the highest correlation, whereas ferulic acid exhibited the lowest correlation. All components showed a positive correlation. Using the Borda method, the components were ranked as follows based on correlation: formononetin > calycosin > ligustrazine > puerarin > ferulic acid.

CONCLUSIONS

The effective components of YYTN exhibited synergistic effects in the treatment of MCAO rats, which could potentially be attributed to their multitarget and multipathway mechanisms. The Borda method-based spectrum-effect correlation analysis provides a coordinated approach to investigate the relationship between fingerprint and pharmacodynamics of traditional Chinese medicine (TCM).

摘要

民族药理学相关性

目前,缺血性中风是一个主要的公共卫生危害。养血清脑颗粒(YYTN)是一种中药方剂,对缺血性中风后继发性脑缺血再灌注损伤(CIRI)具有潜在的治疗作用。然而,需要进一步研究来理解 YYTN 治疗 CIRI 的潜在机制以及相关的谱效机制。

研究目的

探讨 YYTN 治疗大鼠 CIRI 有效成分(总黄酮、总皂苷、总生物碱和总酚酸)指纹图谱与药效指标的协同相关性。

方法

采用高效液相色谱法(HPLC)建立了 YYTN 中 5 种特定成分(川芎嗪、葛根素、阿魏酸、毛蕊异黄酮和芒柄花素)在大脑中动脉闭塞(MCAO)大鼠模型中的指纹图谱,并对血浆样品中的峰面积进行了定量。采用Criteria Importance Through Intercriteria Correlation(CRITIC)法综合肿瘤坏死因子-α(TNF-α)、细胞色素 c(Cyt-C)和总超氧化物歧化酶(T-SOD)等药效指标,建立综合评价指标。采用灰色关联分析(GRA)、相关分析(CA)和偏最小二乘回归(PLSR)进行谱效相关性分析。然后应用 Borda 法对所得结果进行整合。

结果

在 MCAO 大鼠中,YYTN 的有效成分降低了 TNF-α和 Cyt-C,增加了 T-SOD,表明其具有抗炎、抗凋亡和抗氧化作用。谱效 CA 揭示了 5 种主要成分的色谱峰与综合药效评价指数之间存在一定的关联。其中,芒柄花素相关性最高,阿魏酸相关性最低。所有成分均表现出正相关。采用 Borda 法,根据相关性对成分进行排序:芒柄花素>毛蕊异黄酮>川芎嗪>葛根素>阿魏酸。

结论

YYTN 的有效成分在治疗 MCAO 大鼠方面表现出协同作用,这可能归因于其多靶点、多途径的作用机制。基于 Borda 法的谱效相关性分析为研究中药指纹图谱与药效之间的关系提供了一种协调的方法。

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