{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T05:20:28Z","timestamp":1787462428796,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82274082"],"award-info":[{"award-number":["82274082"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82274082"],"award-info":[{"award-number":["82274082"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Acute myocardial infarction (AMI) is a leading cause of death worldwide, characterised by systemic inflammation and metabolic disorders. Tetrahydropalmatine (THP) and berberine (BBR) are major alkaloids derived from Corydalis yanhusuo and Coptis chinensis, respectively, both of which have been shown to be cardioprotective; however, whether their mechanisms differ remains unclear. In this study, we systematically compared THP and BBR in treating AMI using integrated spatial metabolomics (AFADESI-MSI), untargeted metabolomics, lipidomics, and molecular biology. The results showed that both compounds improved cardiac function, reduced fibrosis, and suppressed inflammation. Multi-omics revealed that although both regulate glycerophospholipid metabolism, their pathway preferences and functional roles diverge: THP primarily affects linoleic acid and acetylcholine metabolism with a greater propensity to restore membrane structural integrity, whereas BBR targets ether phospholipids and sphingolipids with preferential anti-inflammatory lipid modulation. At the enzymatic level, both downregulated CHK\u03b1, PEMT, ChAT, and PDHA1. A key difference is that THP uniquely upregulated acetylcholinesterase (AChE) mRNA expression, an effect absent with BBR. Spatial metabolomics directly visualised that both compounds reverse the accumulation of pro-inflammatory lysophosphatidylcholines (LPCs) and restore structural phosphatidylcholines (PCs) in the infarct region, thereby re-establishing regional lipid homeostasis. To our knowledge, this is the first integrated multi-omics comparison to suggest shared and distinct mechanisms of THP and BBR in AMI. Notably, the differential regulation of AChE, as visualised by spatial omics, may serve as a molecular basis for understanding their distinct therapeutic features, although further validation at the protein and enzymatic activity levels is warranted.<\/jats:p>","DOI":"10.3390\/ijms27167484","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T09:31:59Z","timestamp":1787304719000},"page":"7484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial Metabolomics Reveals the Common and Compound-Specific Pharmacological Mechanisms of Two Alkaloids Against Infarcted Myocardium"],"prefix":"10.3390","volume":"27","author":[{"given":"Zixuan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102401, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102401, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Jiao","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102401, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huoli","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102401, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianzhen","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102401, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herong","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102401, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Bai","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haimin","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102401, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1016\/j.jacc.2018.08.1038","article-title":"Fourth Universal Definition of Myocardial Infarction (2018)","volume":"72","author":"Thygesen","year":"2018","journal-title":"J. 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