Akt inhibitor deguelin aggravates inflammation and fibrosis in myocarditis.

Myocarditis is characterized by inflammatory cell infiltration in myocardial stroma. Attenuation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β is a reliable mark for improving the prognosis. Protein kinase B (Akt) plays an important role in the development and progression of myocarditis. The specific role of the natural inhibitor of Akt, Deguelin, on myocarditis has not been reported. In this study, we used deguelin to investigate the effects of natural Akt inhibitor on myocarditis in experimental autoimmune myocarditis (EAM) rats.EAM rat models were made by using Lewis rats and Deguelin was injected intraperitoneally on day 3, 6, 9, 12 and 15 after successful modeling. On day 18, rats were sacrificed and the heart weight (HW)/ body weight (BW) ratio were measured. The pathological changes, pathological scores and fibrosis area were evaluated after H.&E. and Masson's trichrome staining. The mRNA levels of TNF-α and IL-1β were measured by RT-qPCR, while the protein expressions of TNF-α and IL-1β were detected by immunohistochemical staining and Western bolt. The protein expressions of Akt, Akt1, phosphorylated (p-) Akt and nuclear factor (NF)-κB were detected by Western bolt.We found that the TNF-α and IL-1β levels, inflammatory scores and fibrosis areas were markedly increased after 18 days deguelin administration.Akt inhibition with deguelin may aggravate myocarditis of EAM rats.