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

IF 5.4 2区医学 Q1 CHEMISTRY, MEDICINAL Journal of ethnopharmacology Pub Date : 2025-04-09 Epub 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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七龙胶囊通过调节P2Y12/AC/cAMP信号通路调节多发性脑梗死后小胶质细胞功能，抑制血小板活化

多发性脑梗死（multiple cerebral infarction, MCIs）是一种常见的缺血性中风类型，它会影响甚至危及患者的生命。七龙胶囊（QLC）是由补阳还五汤（BYHWD）制成的中成药，适用于治疗缺血性脑卒中后遗症，如多发性脑梗死性痴呆（MID）。然而，其生物学机制尚未得到充分探讨。本研究的目的是探讨QLC治疗轻度认知损伤及其后遗症的机制。方法以7 ~ 8周龄、体重210 ~ 230 g的SD大鼠为MCI模型，采用QLC干预。通过观察MCI模型大鼠体重、神经功能评分、前肢握力和水迷宫测试结果，评价QLC对MCI模型大鼠神经行为的影响。采用血红素-伊红（HE）染色、银染色、透射电镜和正电子发射断层扫描/计算机断层扫描（PET/CT）观察芪多糖对神经元和小胶质细胞的影响。通过血小板聚集率和流式细胞术（FCM）观察芪多糖对血小板的影响。最后，通过ELISA、免疫荧光染色和Western blotting验证QLC的作用机制。结果QLC通过改善大脑组织和神经元损伤，改善MCI后的神经行为测量、前肢握力和空间记忆。QLC还能有效抑制MCI后的炎症反应。我们还发现，QLC可以降低小胶质细胞的活化，降低转运蛋白18kda （TSPO）的表达。QLC可以促进血小板聚集，降低CD62p和CD61的表达，表明QLC具有显著的抗血小板聚集作用。在分子水平上，我们发现QLC影响环磷酸腺苷（cAMP）和环鸟苷（cGMP）的含量，降低重组嘌呤能受体P2Y、G蛋白偶联12 （P2Y12）在小胶质细胞中的表达，调控P2Y12/腺苷酸环化酶(AC)/cAMP信号通路。结论sqlc可改善MCI所致大鼠神经元坏死和MID，并具有抗血小板聚集作用。QLC可能通过调节P2Y12/AC/cAMP来治疗MID。

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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.