Tectoridin modulates intertwined molecular pathways in metabolic syndrome: insights from network pharmacology,...

Ethnopharmacology explores the traditional use of natural substances, particularly plants, to treat diseases across various cultures. This study investigates Tectoridin, a bioactive isoflavone derived from traditional medicinal plants, for its therapeutic potential in metabolic syndrome using both experimental and computational methods.

Metabolic syndrome is a multifactorial disorder characterised by obesity, insulin resistance, hypertension, and dyslipidemia, increasing the risk of cardiovascular diseases and type 2 diabetes. Due to its complexity, multi-targeted therapeutic strategies are essential. Tectoridin, an isoflavone glycoside isolated from Pueraria thunbergiana (Leguminosae) and Iris tectorum, exhibits potential in modulating metabolic pathways.

This study integrates network pharmacology, molecular docking, and in vivo validation to explore tectoridin's therapeutic efficacy against MetS.

A protein-protein interaction (PPI) network analysis identified 11 hub genes, with EGFR, HSP90AA1, PPARG, TNF-α, and ESR1 playing key roles in MetS regulation. Molecular docking revealed strong binding affinities between tectoridin and these targets (binding energies: EGFR - 8.7 kcal/mol, HSP90AA1 - 8.4 kcal/mol, PPARG - 8.4 kcal/mol, TNF-α - 6.1 kcal/mol, ESR1 - 1.8 kcal/mol). In vivo studies using a high-fat diet-streptozotocin (HFD-STZ)-induced MetS rat model demonstrated that tectoridin significantly reduced BMI (from 214.12 ± 1.14 mg/dL to 99.75 ± 1.69 mg/dL), adiposity index, and liver hypertrophy. Blood glucose levels improved, with tectoridin lowering the glucose area under the curve (AUC) from 319.5 ± 11.49 to 205.21 ± 10.23. Lipid profile analysis showed an increase in HDL (53.61 ± 3.01 mg/dL) and reductions in cholesterol (77.66 ± 3.37 mg/dL), triglycerides (68.6 ± 2.64 mg/dL), and LDL (33.80 ± 2.70 mg/dL). Gene expression analysis confirmed the downregulation of EGFR, HSP90AA1, and TNF-α, with the upregulation of PPARG and ESR1. Furthermore, biochemical analysis, cell viability analysis and histopathological analysis further validated its protective effects on hepatic tissues.

These findings establish tectoridin as a promising multi-target phytopharmaceutical candidate for MetS management, warranting further clinical investigations.