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This hypertrophy, in turn, exacerbates microvascular insufficiency, forming a pathological feedback loop and culminating in persistent cellular stress, inflammatory infiltration, and myocardial fibrosis. This \u201cischemia\u2013hypertrophy\u2013inflammation\u2013fibrosis\u201d interrelationship not only drives pathological remodeling but also significantly elevates the risk of heart failure, arrhythmias, and adverse prognosis. The traditional formula Huayu Qutan Formula (HYQT), used clinically for years, has been shown to significantly enhance cardiac function in HCM patients. However, its underlying mechanisms remain poorly elucidated. This study aims to explore HYQT\u2019s therapeutic effects on HCM and to reveal its intrinsic mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Blood-absorbed constituents of HYQT were identified using UHPLC-MS, followed by network pharmacology analysis and molecular docking to predict potential targets and key signaling pathways. An isoproterenol (ISO)-induced HCM mouse model, along with parallel in vitro injury models using H9C2 cardiomyocytes and human cardiac microvascular endothelial cells (HCMECs), was established to systematically assess the in vivo and in vitro effects of HYQT. To comprehensively evaluate HYQT\u2019s modulation of myocardial hypertrophy, fibrosis, and angiogenesis, echocardiography, laser speckle perfusion imaging, immunohistochemistry, western blotting, reactive oxygen species (ROS) assays, and wound-healing assays were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>UHPLC-MS analysis identified 31 blood-absorbed bioactive components of HYQT. Integrated network pharmacology and molecular docking analyses identified the MAPK and HIF-1\u03b1-signaling pathways as key therapeutic targets. In ISO-induced HCM mice, HYQT significantly improved cardiac morphology and function, reduced hypertrophic markers (ANP and BNP), inhibited myocardial collagen deposition, attenuated fibrosis, restored microvascular perfusion and density, and suppressed oxidative stress (MDA and ROS) and pro-inflammatory cytokine expression (TNF-\u03b1 and IL-6). Mechanistically, in vitro experiments supported a cell-type\u2013resolved, parallel regulatory effect: in HCMECs, HYQT-containing serum enhanced migration and viability, reduced ROS accumulation, and activated HIF-1\u03b1\/VEGF-mediated angiogenic signaling, thereby alleviating microvascular dysfunction; concurrently, in H9C2 cardiomyocytes, HYQT inhibited phosphorylation of ERK, p38, and JNK, restored mitochondrial membrane potential, and reduced cell death, thereby mitigating hypertrophic remodeling and its downstream fibrotic progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HYQT effectively ameliorates key pathological features of HCM, including myocardial hypertrophy, fibrosis, and microvascular dysfunction. As a clinically used herbal formulation, this study provides mechanistic insight into its therapeutic effects by revealing a cell-type\u2013resolved, myocardium\u2013microvasculature regulatory framework. Specifically, HYQT suppresses MAPK signaling to attenuate cardiomyocyte hypertrophy while enhancing HIF-1\u03b1\u2013mediated angiogenesis to improve the microvascular environment. These simultaneous effects are associated with mitigation of pathological cardiac remodeling, suggesting that HYQT may serve as a promising multi-target therapeutic strategy for HCM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13020-026-01400-5","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:21:48Z","timestamp":1780039308000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Huayu-qutan formula ameliorates hypertrophic cardiomyopathy by regulating MAPK and HIF\u20111\u03b1-signaling pathways"],"prefix":"10.1186","volume":"21","author":[{"given":"Wei","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Shi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Jie","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"issue":"16","key":"1400_CR1","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1161\/CIRCULATIONAHA.109.934059","volume":"122","author":"K Abozguia","year":"2010","unstructured":"Abozguia K, Elliott P, McKenna W, Phan TT, Nallur-Shivu G, Ahmed I, et al. 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