Total flavonoids of Selaginella tamariscina (Beauv.) Spring alleviate glucolipid metabolic disorders in rats and endothelial injury in TNF-α-induced cells
Abstract
To evaluate the effects of total flavonoids of Selaginella tamariscina (Beauv.) Spring (TFST) on glucolipid metabolic disorders (GLMD) in rats and TNF-α-stimulated human umbilical vein endothelial cells, as well as elucidate the underlying mechanisms. A rat model of GLMD was established using a high-fat diet combined with vitamin D 3 . Body weight and liver weight were recorded, and serum lipid profiles and biochemical parameters were determined. Hepatic histopathological changes were evaluated using hematoxylin and eosin (H&E) staining. The potential mechanisms underlying the protective effects of TFST against vascular inflammation were further explored using network pharmacology and molecular docking. In in vitro studies, following TNF-α stimulation and TFST treatment, the levels of inflammatory mediators in cell culture supernatants were measured by ELISA. The subcellular localization of NF-κB p65 was detected by immunofluorescence microscopy to evaluate its nuclear translocation. In addition, Western blot analysis was performed to quantify the protein expression levels of NF-κB p65, IkBo, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin. TFST significantly normalized body weight, liver weight and liver index ( P < 0.05) and improved lipid parameters ( P < 0.05), while reducing plasma viscosity ( P < 0.05) in GLMD rats. It also reduced hepatic lipid accumulation and injury, and enhanced the activities of rate-limiting enzymes involved in hepatic lipid metabolism ( P < 0.05). In the endothelial inflammatory cell model, TFST decreased the levels of inflammatory mediators and oxidative stress ( P < 0.05). Furthermore, TFST downregulated the protein expression of VCAM-1, E-selectin, and NF-κΒ p65, and restored IκBα levels ( P < 0.05), while also suppressing NF-κΒ p65 nuclear translocation. TFST ameliorates GLMD and vascular endothelial inflammation via NF-κΒ pathway inhibition.