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Guanxinning tablets (GXNT), a botanical drug composed of the blood-activating herbs <jats:italic>Salvia miltiorrhiza<\/jats:italic> Bunge. and <jats:italic>Ligusticum striatum<\/jats:italic> DC., are widely used in the treatment of cardiovascular diseases. However, the active ingredients and their molecular mechanisms are yet to be fully understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We evaluated the anti-hypertrophic effects of GXNT and screened its active substances via cardiac function live-imaging on an aristolochic acid A-stimulated zebrafish cardiac hypertrophy model, and through F-actin immunostaining on a phenylephrine-induced hypertrophic NRCMs model. Additionally, the protective effects of GXNT\u2019s active substances were analyzed in a mouse model of cardiac hypertrophy using echocardiography, histopathology analysis, and western blotting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The anti-hypertrophic effects of GXNT were assessed using an aristolochic acid A-stimulated zebrafish model and phenylephrine-induced hypertrophic NRCMs. GXNT demonstrated significant anti-hypertrophic effects in both models. Phenotypic screening identified Senkyunolide I (Sen I) from <jats:italic>Ligusticum striatum<\/jats:italic> as the active component in the zebrafish model, while Salvianolic acid B (Sal B) and Rosmarinic acid from <jats:italic>Salvia miltiorrhiza<\/jats:italic> emerged as the key anti-hypertrophic compound in NRCMs. In a mouse model of isoproterenol-induced cardiac hypertrophy, Sal B and Sen I showed synergistic effects, improving cardiac function, reducing oxidative stress, and suppressing inflammation. Mechanistically, transcriptomic sequencing highlighted cooperative modulation of MAP3K1 signaling by the two compounds. Notably, siRNA-mediated knockdown of MAP3K1 in cardiomyocytes attenuated the hypertrophic phenotype, supporting its essential role in the pathological process. Molecular docking and dynamic simulations further supported their binding potential to MAP3K1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These findings underscore GXNT\u2019s potent anti-hypertrophic effects, possibly driven by the synergistic actions of Sal B and Sen I, and offer insights into its therapeutic potential through MAP3K1 signaling regulation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13020-025-01189-9","type":"journal-article","created":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:02:47Z","timestamp":1759017767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Salvianolic acid B and Senkyunolide I synergistically alleviate cardiac hypertrophy and regulate MAP3K1 signaling"],"prefix":"10.1186","volume":"20","author":[{"given":"Changtong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2342-3319","authenticated-orcid":false,"given":"Lu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"1189_CR1","doi-asserted-by":"publisher","first-page":"543","DOI":"10.2217\/14796678.1.4.543","volume":"1","author":"A Muller","year":"2005","unstructured":"Muller A, Simonides WS, Muller A, Simonides WS. 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