Mechanisms underlying the therapeutic effects of Dendrobium officinale in treating metabolic syndrome based on clinical datasets, network pharmacology, molecular docking and enzyme kinetic assay

Background: Metabolic syndrome (MetS) significantly increases risks for diabetes and cardiovascular diseases. Dendrobium officinale, a Traditional Chinese Medicine (TCM), shows potential in treating MetS, yet its active components and mechanisms remain unclear. Objectives: To identify the key active constituents of D. officinale and elucidate their mechanisms against MetS using integrated clinical and experimental approaches. Methods: A clinical trial (n=37) evaluated D. officinale powder efficacy in MetS patients. Network pharmacology predicted active compounds and targets. Molecular docking assessed compound-target interactions. Enzyme kinetic assay measured inhibition of protein tyrosine phosphatase 1B (PTP1B). Results: Clinical results showed significant improvements in triglycerides (TG), fasting blood glucose (FBG), body mass index (BMI), and waist circumference. Network pharmacology and molecular docking identified Vicenin II and Schaftoside as key compounds targeting PTP1B. Enzyme assays confirmed both potently inhibited PTP1B activity (IC50 values: Vicenin II 6.94±0.22 ?M; Schaftoside 6.33±0.21 ?M), stronger than positive control NaVO4 (IC50 12.65±1.60 ?M). Kinetic analysis indicated Vicenin II as a competitive inhibitor and Schaftoside as mixed-type. Conclusion: Dendrobium officinale effectively improves MetS parameters. Vicenin II and Schaftoside are identified as key active constituents, likely exerting therapeutic effects through potent PTP1B inhibition.