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

Abstract

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 1−42induced apoptosis by inhibiting CDK5 activation.

Phytochemical Profile of Alkaloid Extract from Dendrobium huoshanense and Inhibitory Effects against Oxidative Stress in H2O2‐Induced PC12 Cells

“…Previous studies had shown that dendrobine treatment brought a similar trend in Aβ 1-42 -induced PC12 cell morphology. [44] Moreover, it was noted that DHSAE-3 obviously attenuated the pathological features, and almost restored the normal cell morphology (Figure 6F vs. Figure 6A).…”

“…nobile alkaloids can significantly improve the viability and apoptosis rate of PC12 cell induced by Aβ 25-35 , [28] and dendrobine suppressed Aβ 1-42 -induced neurotoxicity in PC12 cells. [44] Besides, SG-168 isolated from D. nobile Lindley was identified as a neuroprotective agent in H 2 O 2 -induced PC12 cells assay. [45] Therefore, we established H 2 O 2 -treated PC12 cells screening program to discover the neuroprotection of crude/purified DHAEs, and DHAE, DHSAE-3, and DHSAE-3' were subjected to the following assay.…”

Dendrobium Nobile Alcohol Extract Extends the Lifespan of Caenorhabditis elegans via hsf-1 and daf-16

“…Dendrobine, known for its antiaging and neuroprotective effects, inhibits dopamine-related neuronal apoptosis in PD models [ 43 ] and reduces SASP factor expression in chondrocytes, suggesting potential for osteoarthritis treatment [ 44 ]. Dendroxine protects PC12 cells from Aβ1-42-induced neurotoxicity by inhibiting CDK5 [ 45 ]. Nobilonine reduces lipopolysaccharides in rats [ 46 ].…”

Dendrobine Ameliorates Glucocorticoid-Induced Osteoporosis by Promoting Osteogenesis through JNK/p38 MAPK Pathway Activation and GR Nuclear Translocation Inhibition

“…Cheng-Chen Zhang et al found that DEN can enhance Tyr15 phosphorylation through tight binding with CDK5. 33 The specific regulatory effect of DEN on the phosphorylation of p38 and JUN needs further research.…”

“…Noteworthy, studies certified that DEN regulated the phosphorylation of p38 and JNK in osteoclasts and lung cancer cells, , but the direct effect of DEN on p38 and JUN has not been demonstrated, which is also the weakness of our study. Cheng-Chen Zhang et al found that DEN can enhance Tyr15 phosphorylation through tight binding with CDK5 . The specific regulatory effect of DEN on the phosphorylation of p38 and JUN needs further research.…”