{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:02:00Z","timestamp":1790920920193,"version":"4.1.0"},"reference-count":25,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Municipal Commission of Health and Family Planning","award":["ZY (2021-2023)-0208"],"award-info":[{"award-number":["ZY (2021-2023)-0208"]}]},{"name":"Shanghai Municipal Commission of Health and Family Planning","award":["82074054"],"award-info":[{"award-number":["82074054"]}]},{"name":"Shanghai Municipal Commission of Health and Family Planning","award":["82004144"],"award-info":[{"award-number":["82004144"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZY (2021-2023)-0208"],"award-info":[{"award-number":["ZY (2021-2023)-0208"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074054"],"award-info":[{"award-number":["82074054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82004144"],"award-info":[{"award-number":["82004144"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our previous studies revealed the protection of stachydrine hydrochloride (STA) against cardiopathological remodeling. One of the underlying mechanisms involves the calcium\/calmodulin-dependent protein kinase \u2161 (CaMKII). However, the way STA influences CaMKII needs to be further investigated. The nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2)-coupled reactive oxygen species (ROS) overproduction putatively induces the oxidative activation of CaMKII, resulting in the occurrence of pathological cardiac remodeling and dysfunction in experimental models of mice. Thus, in this study, we assessed the role of the NOX2-ROS signal axis in STA cardioprotection. The transverse aortic constriction (TAC)-induced heart failure model of mice, the phenylephrine-induced hypertrophic model of neonatal rat primary cardiomyocytes, and the H2O2-induced oxidative stress models of adult mouse primary cardiomyocytes and H9c2 cells were employed. The echocardiography and histological staining were applied to assess the cardiac effect of STA (6 mg\/kg\/d or 12 mg\/kg\/d), which was given by gavage. NOX2, ROS, and excitation-contraction (EC) coupling were detected by Western blotting, immunofluorescence, and calcium transient-contraction synchronous recordings. ROS and ROS-dependent cardiac fibrosis were alleviated in STA-treated TAC mice, demonstrating improved left ventricular ejection fraction and hypertrophy. In the heart failure model of mice and the hypertrophic model of cardiomyocytes, STA depressed NOX2 protein expression and activation, as shown by inhibited translocation of its phosphorylation, p67phox and p47phox, from the cytoplasm to the cell membrane. Furthermore, in cardiomyocytes under oxidative stress, STA suppressed NOX2-related cytosolic Ca2+ overload, enhanced cell contractility, and decreased Ca2+-dependent regulatory protein expression, including CaMK\u2161 and Ryanodine receptor calcium release channels. Cardioprotection of STA against pressure overload-induced pathological cardiac remodeling correlates with the NOX2-coupled ROS signaling cascade.<\/jats:p>","DOI":"10.3390\/ijms241814369","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T04:53:05Z","timestamp":1695271985000},"page":"14369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Stachydrine Hydrochloride Regulates the NOX2-ROS-Signaling Axis in Pressure-Overload-Induced Heart Failure"],"prefix":"10.3390","volume":"24","author":[{"given":"Shuang","family":"Lu","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyang","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songru","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengwei","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Shan","sequence":"additional","affiliation":[{"name":"Public Experiment Platform, School of Traditional Chinese Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Intergrative Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihua","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Public Experiment Platform, School of Traditional Chinese Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3040-5781","authenticated-orcid":false,"given":"Rong","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, SHUTCM, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1161\/CIR.0000000000000558","article-title":"Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association","volume":"137","author":"Benjamin","year":"2018","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jchf.2017.12.006","article-title":"Innovation in Heart Failure Treatment: Life Expectancy, Disability, and Health Disparities","volume":"6","author":"Xie","year":"2018","journal-title":"JACC Heart Fail."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Writing Committee Members, and ACC\/AHA Joint Committee Members (2022). 2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure. 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