Baicalein ameliorated obesity-induced cardiac dysfunction by regulating the mitochondrial unfolded protein response through NRF2 signaling

• DOI: 10.1016/j.phymed.2024.155441
• Publication Date: 2024-02-10T16:19:49Z
• Authors: Lulu Guo; Junle Yang; Wenting Yuan; Chongyao Li; Hui Li; Yang Yang; Runqing Xue; Kangkang Yan
• Keywords: Baicalein

The mitochondrial unfolded protein response (UPRmt) is the first line of defense against dysfunction in several diseases. Baicalein, which an extract Scutellaria baicalensis Georgi roots, exerts mitoprotective effects on metabolic disorders and cardiovascular However, it remains unclear whether baicalein alleviates obesity-induced cardiac damage through UPRmt. present research designed to clarify role lipotoxicity-induced myocardial apoptosis investigated UPRmt-related mechanism. In vitro experiment, palmitic acid (PA)-treated AC16 cardiomyocytes were established mimic injury. After pretreatment cells with baicalein, levels cell vitality, apoptosis, membrane potential, oxidative stress, proteins determined. Additionally, treated ML385 or siRNA explore regulation UPRmt by NRF2 signaling. vivo male db/db mice administered for 8 weeks used validate induced obesity, UPRmt, NRF2-related pathway. cardiomyocytes, PA dose-dependently increased expression markers (HSP60, LONP1, ATF4, ATF5). This increase was accompanied enhanced production ROS, reduced elevated cytochrome c, cleaved caspase-3, Bax/Bcl2, eventually leading apoptosis. Baicalein treatment reversed activation impeded mitochondrial-mediated Moreover, downregulation its inhibitor diminished baicalein-mediated signaling inhibition triggered dysfunction. deficiency more intensely activated resulting stress PA-induced thus indicating that plays a vital homeostasis regulation. study mice, inhibited antioxidant capacity, attenuated NRF2-activated To our best knowledge, these results provide insight inhibits induce protective effect cardiomyocyte via activating suggest new