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Effect of Naoxintong Capsule on Microglia and Proteomics of Cortex After Myocardial Infarction in Rats

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Abstract

Neuroinflammation caused by microglia in the central nervous system (CNS) is observed after myocardial infarction (MI). However, the inflammatory response mechanism remains unclear. BuChang Naoxintong capsule (NXT) is a Chinese medicine for treating ischemic cardio-cerebrovascular diseases, requiring more studies to understand the pharmacodynamic mechanism. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in rats. Additionally, histopathological staining in the left ventricular (LV) and immunofluorescence within the brain cortex after 1 d and 7 d of MI were performed to determine the NXT pharmacodynamic action and best administration dosage. Proteomics helped obtain the essential proteins related to neuroinflammation and MI in the heart and brain tissue after 7 d of MI. Based on TTC, HE, Masson, and immunofluorescence staining results of CD206 and IBA-1, NXT demonstrated a better pharmacodynamic action towards myocardial injury and neuroinflammation after 7 d of MI. Moreover, the human equivalent dosage of NXT (220 mg/kg) became the best administration dose. The proteome bioinformatics analysis in the LV and brain cortex was performed. Thus, the elongation of very long-chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) became critical proteins related to MI and neuroinflammation. The western blotting results indicated that ABCG4 expression possessed the same trend as the proteomics results. The auto-dock results revealed that ABCG4 had a good binding ability with Ferulic acid, Paeoniflorin, and Tanshinone II A, the key ingredients of NXT. The cellular thermal shift assay results demonstrated that ABCG4 showed better thermal stability post-NXT treatment. NXT can improve myocardial injury, such as heart infarct size, pathological injury, myocardial fibrosis, and inflammatory cell infiltration. Additionally, brain neuroinflammation induced by microglia after MI affects the expression and structure of ABCG4. Thus, ABCG4 could be the key protein associated with MI and neuroinflammation.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

I would first like to thank the China Academy of Chinese Medical Sciences for carrying out the study. I would like to thank my supervisor Shihuan Tang, for his guidance through each stage of the process, and also Professor Hongjun Yang, and Hongwei Wu, for their professional advice for this paper. I would like to thank my team members, Yuxin Lei, Jing Zhang, and Jing Xu, for their wonderful collaboration and support.

Funding

This work was supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(N0.CI2021A00605), the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (No.CI2021B015), National Natural Science Foundation of China (No.81973711).

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Authors and Affiliations

  1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Mengli Chang, Yuxin Lei, Jing Zhang, Jing Xu, Hongwei Wu & Shihuan Tang

  2. Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, 100700, China

    Hongjun Yang

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  1. Mengli Chang
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Contributions

Mengli Chang carried out the animal experiments and wrote the paper, Mengli Chang and Jing Xu conducted the analyses, Yuxin Lei and Jing Zhang carried out the picture rendering, and Shihuan Tang and Hongjun Yang conceived the framework of the paper. In the process of revising the paper, Hongwei Wu modified the language and corrected the mistakes in the paper. All authors have made a significant contribution to the work and gave final approval for the version to be published.

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Correspondence to Jing Xu, Hongwei Wu, Shihuan Tang or Hongjun Yang.

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The experiments were approved by the China Academy of Chinese Medical Sciences' Administrative Panel on Laboratory Animal Care and performed under the institutional guidelines and ethics of the committee as part of the China Academy of Chinese Medical Sciences (ERCCACMS21-2111–02).

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Chang, M., Lei, Y., Zhang, J. et al. Effect of Naoxintong Capsule on Microglia and Proteomics of Cortex After Myocardial Infarction in Rats. Mol Neurobiol 61, 2904–2920 (2024). https://doi.org/10.1007/s12035-023-03724-x

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