Qilong capsule regulates microglial function and inhibits platelet activation after multiple cerebral infarctions by regulating the P2Y12/AC/cAMP signalling pathway

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-03-06 DOI:10.1016/j.jep.2025.119586

Min Zhan , Xiaoyu Zheng , Jiaming Gao , Shengnan Shi , Wenting Song , Mingjiang Yao , Linjuan Sun , Xiaodi Fan , Yehao Zhang , Jianxun Liu

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Abstract

Ethnopharmacological relevance

Multiple cerebral infarctions (MCIs) represent a common type of ischaemic stroke that affects or even endangers a patient's life. Qilong capsule (QLC), a Chinese patent medicine made from Buyang Huanwu Decoction (BYHWD) is suitable for treating the sequelae of ischaemic stroke, such as multi-infarct dementia (MID). However, its biological mechanism has not been fully explored.

Ami of the study

The aim of this study was to explore the mechanism of QLC in treating MCI and its sequelae.

Methods

Male SD rats aged 7–8 weeks and weighing 210–230 g were used as an MCI model, and QLC was used as interventions. The neurobehavioural effects of QLC on MCI model rats were evaluated by observing body weight, neurological function score, and forelimb grip and water maze test results. The effects of QLC on neurons and microglia were observed via haematoxylin‒eosin (HE) staining, silver staining, transmission electron microscopy and positron emission tomography/computed tomography (PET/CT). The effects of QLC on platelets were observed via the platelet aggregation rate and flow cytometry (FCM). Finally, the mechanism of QLC was verified via ELISA, immunofluorescence staining and Western blotting.

Results

These experiments showed that QLC improves neurobehavioural measures, forelimb grip strength, and spatial memory after MCI by ameliorating brain tissue and neuronal damage. QLC also effectively inhibited the inflammatory response after MCI. We also found that QLC can decrease microglia activation and reduce the expression of translocator protein 18 kDa (TSPO). QLC can improve platelet aggregation and reduce the expression of CD62p and CD61, indicating that QLC has a significant anti-platelet aggregation effect. At the molecular level, we found that QLC affects the content of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), reduces the expression of recombinant purinergic receptor P2Y, G protein coupled 12 (P2Y₁₂) in microglia, and regulates the P2Y₁₂/adenylate cyclase (AC)/cAMP signalling pathway.

Conclusions

QLC can ameliorate neuronal necrosis and MID induced by MCI and has an antiplatelet aggregation effect in rats. QLC may treat MID by regulating P2Y₁₂/AC/cAMP.

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.