LAUSR

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 (Aβ1−42)‐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 Aβ1−42‐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 Aβ1−42‐induced apoptosis by inhibiting CDK5 activation.