Inhibition of 12/15-LO ameliorates CVB3-induced myocarditis by activating Nrf2

Cardiac 12/15-lipoxygenase (12/15-LO) was reported to be markedly up-regulated and involved in the development of heart failure. Nuclear factor E2-related factor 2 (Nrf2) plays anti-inflammatory and anti-oxidation roles in response to oxidative stress. However, the role of 12/15-LO in viral myocarditis (VMC) and its underlying molecular mechanism have not yet been elucidated. Here, we demonstrated that 12/15-LO was up-regulated and Nrf2 was down-regulated in coxsackievirus B3 (CVB3)-infected mice and cardiac myocytes. Baicalein, the specific inhibitor of 12/15-LO, was employed to investigate the role of 12/15-LO and its underlying mechanism in VMC. We found that baicalein treatment alleviated CVB3-induced VMC mouse models, as demonstrated by less inflammatory lesions in the heart tissues and less CK-MB level. Moreover, baicalein treatment attenuated CVB3-induced inflammatory cytokine production and oxidative stress. Mechanistic analysis suggested that baicalein treatment relieved CVB3-induced reduction of Nrf2 and heme oxygenase-1 (HO-1) expressions. Taken together, our study indicated that inhibition of 12/15-LO ameliorates VMC by activating Nrf2, providing a new therapeutic strategy for the therapy of VMC.