{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:36:55Z","timestamp":1786649815403,"version":"build-2736575974"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>INTRODUCTION:<\/jats:title>\n                    <jats:p>Chronic sympathetic stress contributes significantly to the cardiac hypertrophy (CH) development. Currently, several pharmacological agents and surgical options are available for the treatment of CH. However, available treatment options are associated with side effects and surgical complications. The published reports indicated the PKM2 substantial role in numerous illnesses. Furthermore, the effect of shikonin (SK), a nonselective PKM2 inhibitor, on PKM2\/c-Myc\/PTBP1\/HIF-1\u03b1 signaling in the CH model has never been explored. Thus, in this study, we explore the effect of SK on the PKM2-mediated c-Myc\/PTBP1\/HIF-1\u03b1 signaling pathway in isoproterenol (ISO)-induced CH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS:<\/jats:title>\n                    <jats:p>The preclinical rat model of pathological CH was developed by subcutaneous (s.c.) administration of ISO (5 mg\/kg\/day) over 14 days. ISO-treated rats were orally received SK (2 and 4 mg\/kg\/day) for a period of 14 days. After all treatment completion, animals were anesthetized for electrocardiogram (ECG), blood pressure, and ventricular function recording. Afterward, animal blood samples were isolated, and then animals were sacrificed for further molecular and histopathology studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Fourteen days treatment of SK showed significant improvement in ECG, fibrosis, inflammation, and cardiac function. Moreover, PKM2, PTBP1, c-Myc, and HIF-1\u03b1 expressions were upregulated, while PKM1 expression was downregulated in ISO-treated rats, which was reversed by SK treatment in ISO-induced CH rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION:<\/jats:title>\n                    <jats:p>Thus, our results demonstrated that SK modulates the PKM2\/c-Myc\/PTBP1\/HIF-1\u03b1 pathway mediated by PKM2 inhibition, which might be responsible for SK-mediated cardioprotection in ISO-induced CH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/ijp.ijp_742_24","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T15:01:04Z","timestamp":1752073264000},"page":"126-133","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Cardioprotective potential of shikonin in cardiac hypertrophy is mediated through PKM2\/c-Myc\/PTBP1\/HIF-1\u03b1 signaling pathway"],"prefix":"10.4103","volume":"57","author":[{"given":"Mohd","family":"Rihan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sahibzada Ajit Singh Nagar, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam Sunder","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sahibzada Ajit Singh Nagar, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"R1-20260421","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1056\/NEJM199910213411706","article-title":"Signaling pathways for cardiac hypertrophy and failure","volume":"341","author":"Hunter","year":"1999","journal-title":"N Engl J 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