Tectoridin modulates intertwined molecular pathways in metabolic syndrome: insights from network pharmacology, molecular docking, and in vivo studies.

Abstract

Ethnopharmacological relevance: 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.

Aims and objectives: 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.

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

Results: 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.

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