Ultrasound-assisted ethanolic extract of Morus nigra fruit alleviates oxidative stress and inflammation via Keap1/Nrf2, dual oxidases, and JAK/ STAT pathways

Morus nigra fruit has therapeutic significance against several clinical manifestations due to polyphenols, flavonoids, and anthocyanins. This research aimed to investigate the antioxidative and anti-inflammatory effects of ultrasound-assisted ethanolic (UAE) extract of M. nigra fruit against cholesterol-fed and cigarette smoke-exposed hypertensive rats. The in vitro antioxidant capacity of UAE extract of M. nigra fruit showed higher antioxidant potential against free radicals through DPPH and FRAP assays. The in vivo administration of UAE extract of M. nigra fruit significantly (p p < 0.05) alleviated serum total oxidant status while significantly (p p < 0.05) improved total antioxidant capacity. Moreover, the qRT-PCR analysis revealed increased expression of Keap1/ Nrf2 signaling pathway genes (NFR-1 and Keap-1) while reduced expression of JAK/STAT (JAK-2, STAT-1, STAT-3) signaling cascade and dual oxidases (Duox-1 and Duox-2) genes. Histopathological findings indicated the mild destruction of cardiac fibers and necrosis. Conclusively, UAE extract of M. nigra fruit exerted antioxidant and anti-inflammatory properties against cholesterol and cigarette smoke-associated oxidative damage and inflammation.