Total flavonoids of Selaginella tamariscina (Beauv.) Spring alleviate glucolipid metabolic disorders in rats and endothelial injury in TNF-α-induced cells

Abstract

Objective: 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.
Methods: A rat model of GLMD was established using a high-fat diet combined with vitamin D₃. 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, IκBα, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin.
Results: 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-κB p65, and restored IκBα levels (P < 0.05), while also suppressing NF-κB p65 nuclear translocation.
Conclusions: TFST ameliorates GLMD and vascular endothelial inflammation via NF-κB pathway inhibition.

Keywords

Selaginella tamariscina (beauv.) Spring / Total flavonoids / Glucolipid metabolic disorders / Metabolic fatty liver disease / Vascular inflammation / NF-κB pathway

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