Modafinil attenuates inflammation via inhibiting Akt/NF-κB pathway in apoE-deficient mouse model of atherosclerosis

Modafinil, an FDA approved wakefulness drug prescribed to narcolepsy patients, has recently been shown to have anti-inflammatory effects and provides protection against neuroinflammation. It is unknown if modafinil can also protect against atherosclerosis, pathogenesis of which implicates inflammation. Using an apoE-deficient mouse model, we tried to elucidate the effects of modafinil treatment on the development of atherosclerosis. We tested serum levels of cytokines. We isolated mouse bone marrow-derived macrophages (BMDMs), detected effect of modafinil on the viability and proliferation of BMDMs, and on oxidized low-density lipoprotein-induced IL-6 and TNF-alpha, and supernatant level of IFN-gamma as well as NF-kappa B activity in BMDMs. Modafinil inhibited the development of atherosclerosis in apoE(-/-) mice. Modafinil suppressed the secretion of pro-inflammatory cytokines IL-6, TNF and IFN-gamma, and promoted secretion of anti-inflammatory cytokines IL-4 and IL-10. Modafinil inhibited viability and proliferation of macrophages by negatively regulating levels of pro-inflammatory cytokines, p-Akt, p-IKB alpha and NF-kappa B activity in macrophages. Modafinil mitigates inflammation in apoE(-/-) atherosclerosis mice via inhibiting NF-kappa B activity in macrophages, and could potentially serve as a therapeutic agent for atherosclerosis.