Regulatory effects of specialized metabolites from Dendrobium albosanguineum on lipid metabolism and adipocyte differentiation

The rising global incidence of obesity underscores the urgent demand for effective therapeutic interventions. Natural products have emerged as promising alternatives; however, identifying candidates that effectively target the complex mechanisms underlying obesity remains a critical challenge. In this study, the specialized metabolites of Dendrobium albosanguineum were investigated for their anti-obesity potential. Methanolic extraction was performed on the entire plant, followed by systematic fractionation and compound elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy. A set of in vitro colorimetric assays was employed to assess pancreatic lipase inhibition, cytotoxicity, intracellular lipid storage, triglyceride content, and glycerol release in murine (3T3-L1) and/or human (PCS-210-010) adipocyte models. In addition, flow cytometry, western blotting analysis, and RT-qPCR were used to evaluate the effects of a chosen metabolite on cell cycle progression and the expression of adipogenesis-related genes and proteins. Eight metabolites were isolated, including bibenzyls (moscatilin, chrysotoxine), lignans (syringaresinol, foliachinenoside C), a sterol (daucosterol), a phenylpropanoid (n-octacosyl-trans-p-coumarate), and flavonoids (rhoifolin, kaempferol-3-O-(2″,6″-dirhamnosyl)glucoside). Among them, foliachinenoside C exhibited the most potent activity, with 94.77 ± 0.85% inhibition of pancreatic lipase (IC₅₀ = 40.73 ± 0.74 µM). It significantly reduced triglyceride levels and promoted glycerol release in both murine and human adipocytes. Mechanistically, foliachinenoside C induced cell cycle arrest at the G0 phase in 3T3-L1 cells and downregulated key adipogenic transcription factors (PPARγ, C/EBPα, SREBP1c) and lipogenic proteins (FAS, PLIN1, LPL, ADPN, FABP4). Moreover, it modulated the AKT/GSK3β and AMPK-ACC signaling pathways, collectively suppressing adipocyte differentiation. These findings position foliachinenoside C as a promising plant-derived compound for obesity pharmacotherapy, warranting further investigation to facilitate its clinical development.