Effect of Dunaliella salina on myocardial ischemia-reperfusion injury through KEAP1/NRF2 pathway activation and JAK2/STAT3 pathway inhibition

Abstract

Myocardial ischemia-reperfusion injury (MIRI) is a life-threatening vascular emergency, in which oxidative stress and excessive inflammation reactions play significant roles. Dunaliella salina is rich in natural beta (β)-carotene, which is considered an antioxidant and anti-cancer compound, preventing night blindness, delaying aging, and regulating immunity. Due to its unique nutritional and functional components, D. salina has the potential to be developed as a nutritional health food. At present, it is unknown whether D. salina can rescue MIRI. The present study aimed at investigating whether D. salina has protective effect on MIRI and at exploring its potential mechanism. We developed a Langendorff perfused heart model in mice. The mice were given D. salina by gavage at a dose of 500 mg/kg for 7 days consecutively. It was found that D. salina could improve left ventricle function and reduce the rate of malignant arrhythmia and infarct size (P < 0.01). Furthermore, D. salina administration increased superoxide dismutase and decreased malondialdehyde content in myocardial tissue (P < 0.01). Importantly, real-time polymerase chain reaction and Western blot results showed that D. salina caused nuclear factor (erythroid-derived 2)-like 2 (NRF2) activation and enhanced the expression of antioxidative genes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) (P < 0.05 and P < 0.01, respectively). At the same time, the phosphorylation of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3) was inhibited (P < 0.05 and P < 0.01, respectively), and proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-6 decreased with D. salina administration (P < 0.05). In conclusion, D. salina has a protective effect on MIRI, which may be mediated by promoting kelch-like ECH-associated protein 1 (KEAP1)/NRF2 pathway and inhibiting JAK2/STAT3 signaling pathway.