Shengmai-Yin resists myocardial ischemia reperfusion injury by inhibiting K27 ubiquitination of absent in melanoma 2.

IF 4.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2025-02-24 DOI:10.1016/j.jep.2025.119553

Xiaojin Xu, Yuanyi Wang, Ke Pei, Chenhan Mao, Fei Fang, Tiantong Zhou, Meng Zhang, Pei-Na Meng, Zilun Wei, Chang Liu, Yang Dai, Rui Yin, Zhaoyang Chen, Xindong Wang

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引用次数: 0

Abstract

Ethnopharmacological relevance: Myocardial ischemia-reperfusion (I/R) injury stands as a significant contributor to cardiovascular disease. Shengmai-Yin (SMY), a traditional Chinese medicine, is widely used in myocardial infarct treatment. However, the specific mechanism of SMY in treating myocardial I/R injury is currently limited.

Aim of study: The study aimed to investigate the therapeutic efficacy of SMY in addressing myocardial I/R injury and elucidate its specific mechanisms.

Materials and methods: The active components of SMY were quantified using Ultra-high performance liquid chromatography-MS/MS (UPLC-MS/MS). Sprague-Dawley (SD) rats were treated with SMY post-I/R model establishment. Cardiac injury was assessed by heart weight to body weight ratio. Left ventricular function and infarct volume were evaluated using ultrasound cardiography and TTC staining. Tissue lesions were examined via hematoxylin-eosin (HE) and Sirius Red staining. Co-Immunoprecipitation (Co-IP) technology explored absent in melanoma 2 (AIM2) and K27 Ubiquitination Modification (K27-Ub) interactions. Immunofluorescence staining detected Apoptosis-associated Speck-like Protein containing a CARD (ASC) and AIM2 co-localization. Adeno-associated Virus (AAV) was used to upregulate AIM2 levels, while Shikonin was used to downregulate AIM2, to explore its roles in SMY's therapeutic effects on I/R injury.

Results: SMY can reduce infarct size and enhance cardiac function. Furthermore, SMY can inhibit tissue fibrosis. Fibrosis markers and proinflammatory factors were reduced after SMY treatment. Serum levels of Lactate Dehydrogenase (LDH) and Creatine Kinase -MB (CK-MB) were also decreased. Mechanistically, SMY inhibits the activation of the AIM2 inflammasome by downregulating the K27 ubiquitination of AIM2. Overexpression of AIM2 reversed the anti-I/R effect of SMY, suggesting that AIM2 plays a crucial role in I/R injury. The AIM2 inhibitor counteracts the therapeutic effect of SMY.

Conclusion: SMY inhibits the K27 ubiquitination modification of AIM2 and inhibits the activation of AIM2 inflammasomes after myocardial I/R injury.

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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.