| First Author | Li H | Year | 2023 |
| Journal | Int J Biol Sci | Volume | 19 |
| Issue | 16 | Pages | 5233-5244 |
| PubMed ID | 37928261 | Mgi Jnum | J:342370 |
| Mgi Id | MGI:7547776 | Doi | 10.7150/ijbs.85204 |
| Citation | Li H, et al. (2023) Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury. Int J Biol Sci 19(16):5233-5244 |
| abstractText | Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced cardiomyopathy, the underlying mechanisms remain incompletely understood. Since apigenin beneficially regulates various aspects of mitochondrial function and dynamics, we asked whether apigenin improves heart function in mice with Dox-induced cardiomyopathy by regulating the mitochondrial unfolded protein response (UPR(mt)). Co-administration of apigenin significantly restored heart function, reduced myocardial swelling, inhibited cardiac inflammation, increased cardiac transcription of UPR(mt)-related genes, and promoted cardiomyocyte survival in Dox-treated mice. In turn, blockade of UPR(mt) abolished the mito- and cytoprotective effects of apigenin, evidenced by decreased ATP production, suppressed mitochondrial antioxidant capacity, and increased apoptosis, in Dox-treated, cultured HL-1 cardiomyocytes. Furthermore, apigenin treatment prevented Dox-induced downregulation of Sirt1 and Atf5 expression, and the beneficial effects of apigenin were completely nullified in Sirt1 knockout (KO) mice or after siRNA-mediated Sirt1 knockdown in vitro. We thus provide novel evidence for a promotive effect of apigenin on UPR(mt) via regulation of the Sirt1/Atf5 pathway. Our findings uncover that apigenin seems to be an effective therapeutic agent to alleviate Dox-mediated cardiotoxicity. |
