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Sibjotang attenuates Doxorubicin‐Induced Cardiac Hypertrophy: Involvement of necroptosis

Doxorubicin is one for the most widely used anti‐neoplastic agents, however severely limited due to its cumulative cardiotoxicity, which develops over time into congestive heart failure. Sibjotang (Shizaotang), traditional herbal medicine formula, has been reported regulates the body fluid blood pressure homeostasis. The present study was aimed at determining the effect and regulatory mechanism of Sibjotang in doxorubicin‐induced cardiotoxicity in H9c2 cells. Immunofluorescence staining analysis showed that Sibjotang decreased doxorubicin‐induced increase in H9c2 cardiomyocytes size in does dependent manner. Pre‐treatment with Sibjotang significantly inhibited doxorubicin‐induced cardiac hypertrophic markers such as ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and β‐MHC (β‐myosin heavy chain) mRNA expression levels. Sibjotang reduced hypertrophy‐associated transcription factor GATA 4 (GATA binding factor 4) expression. Pre‐treatment with Sibjotang significantly inhibited doxorubicin‐induced necroptosis‐associated kinase such as receptor‐interacting serine/threonine‐protein kinase RIPK1 and RIPK3 without affecting cell viability. In conclusion, doxorubicin‐induced cardiac hypertrophy and necroptosis were attenuated by Sibjotang. Therefore, Sibjotang may be potential herbal therapies targeting cardiotoxicity resulting from anti‐cancer agents.