Carvacrol Regulates the Expression of SLC25A6 by Inhibiting VDAC1 to Improve Mitochondrial Function and Reduce...

Carvacrol has been demonstrated to possess anti-inflammatory and antioxidant properties. This study aims to further explore the mechanisms by which carvacrol mitigates LPS-induced human microvascular endothelial cells injury by improving mitochondrial function. An inflammatory injury model of human microvascular endothelial cells was established using LPS. The expression levels of inflammatory cytokines (IL-1β, IL-6, IL-18, TNF-α) were measured. Assessment of apoptosis, necrosis, and proliferation was conducted using the YO-PRO-1/PI apoptosis and necrosis detection kit and EdU assay. The evaluation of oxidative stress levels was facilitated by the use of ROS, MDA, and SOD assay kits. Angiogenic capacity and cytoskeletal changes were also examined. Assessment of mitochondrial function and energy metabolism was achieved by measuring mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP) opening, ROS levels, and ATP production. Western blot analysis was performed to detect the expression of VDAC1 and SLC25A6. The results show that carvacrol significantly reduced LPS-induced expression of IL-1β, IL-6, IL-18, and TNF-α and alleviated the effects of LPS on cell proliferation and apoptosis of HMEC-1. It also decreased oxidative stress levels, inhibited excessive tube formation capacity, and promoted cytoskeletal remodeling. Furthermore, carvacrol has been shown to reduce VDAC1 protein expression, improve mitochondrial function and energy metabolism by regulating MMP, mPTP opening, ROS levels, and ATP production, and increase SLC25A6 protein expression. Importantly, carvacrol and VDAC1 knockdown exhibited similar effects. In the mechanism of inflammatory injury, SLC25A6 may act as a downstream effector of VDAC1. The results of this study demonstrate that carvacrol exerts a protective effect on human microvascular endothelial cells by improving mitochondrial function and alleviating oxidative stress through the inhibition of VDAC1.