Two new alkaloids from Dendrobium nobile Lindl. exhibited neuroprotective activity, and dendrobine alleviated Aβ1-42 -induced apoptosis by inhibiting CDK5 activation in PC12 cells

Dendrobium nobile Lindl. is registered in the Chinese Pharmacopoeia as a traditional medicine. Phytochemical investigation of the ethanol extract of D. nobile Lindl. stems yielded three alkaloid compounds, including two new compounds dendroxine B (2) and denrine B (3) as well as one known compound dendrobine (1). Here, we identified the structure of these compounds using spectroscopic analyses and compared them with those described in previous studies. Compounds 1-3 were found to show protective effect against Amyloid-β 1-42 (Aβ_1-42 )-induced neurotoxicity in rat pheochromocytoma (PC12) cells, among which dendrobine exhibited the most significant neuroprotective effect. Hoechst 33342/propidium iodide staining indicated that dendrobine ameliorated Aβ_1-42 -induced Apoptosis. Moreover, quantitative real-time polymerase chain reaction and western blot analysis analysis demonstrated that dendrobine suppressed the activation of cyclin-dependent kinase 5 (CDK5), upregulated Bcl-2 expression, and downregulated Bax, cyto-c, and Caspase-3 expression. Molecular docking analysis and surface plasmon resonance assay suggested that dendrobine directly bound to CDK5 protein with a KD value of 2.05 × 10^-4 M. In summary, Alkaloids are the neuroprotective constituents of D. nobile Lindl., and dendrobine protected PC12 cells against Aβ_1-42 -induced Apoptosis by inhibiting CDK5 activation.

Alzheimer's disease; Dendrobium nobile Lindl. alkaloids; apoptosis.