Dendrobium alkaloids decrease Aβ by regulating α- and β-secretases in hippocampal neurons of SD rats

Abstract

Background Alzheimer’s disease (AD) is the primary cause of dementia in the elderly. The imbalance between production and clearance of amyloid β (Aβ) is a very early, often initiating factor in AD. Dendrobium nobile Lindl. alkaloids (DNLA) extracted from a Chinese medicinal herb, which have been shown to have anti-aging effects, protected against neuronal impairment in vivo and in vitro. Moreover, we confirmed that DNLA can improve learning and memory function in elderly normal mice, indicating that DNLA has potential health benefits. However, the underlying mechanism is unclear. Therefore, we further explored the effect of DNLA on neurons, which is closely related to learning and memory, based on Aβ. Methods We exposed cultured hippocampal neurons to DNLA to investigate the effect of DNLA on Aβ in vitro. Cell viability was evaluated by MTT assays. Proteins were analyzed by Western blot analysis. Results The cell viability of hippocampal neurons was not changed significantly after treatment with DNLA. But DNLA reduced the protein expression of amyloid precursor protein (APP), disintegrin and metalloprotease 10 (ADAM10), β-site APP cleaving enzyme 1 (BACE1) and Aβ1–42 of hippocampal neurons in rats and increased the protein expression of ADAM17. Conclusions DNLA decreases Aβ by regulating α- and β-secretase in hippocampal neurons of SD rats.

Identification, Biological Activities and Biosynthetic Pathway of Dendrobium Alkaloids

“…Investigation on the mechanisms underlying the neuroprotective effects of DNLA revealed that DNLA prominently improved the neurobehavioral performance and prevented LPS-induced elevation in tumor necrosis factor receptor one via inhibition of phosphorylated p38 mitogen-activated protein kinases and the downstream nuclear factor kappa-B signal pathway ( Li et al, 2011 ; Ng et al, 2012 ). Moreover, DNLA decreased the level of intracellular amyloid β peptide (Aβ) by improving impaired autolysosomal proteolysis in amyloid precursor protein/presenilin one mice ( Nie et al, 2018 ), and regulating α- and β-secretase in hippocampal neurons of Sprague-Dawley rats ( Huang J. et al, 2019 ). The reduction of Aβ attenuated Aβ 25–35 -induced spatial learning and memory impairments by increasing the protein expression of neurotrophic factors, such as brain-derived neurotrophic factor, ciliary neurotrophic factor, and glial cell line-derived neurotrophic factor ( Nie et al, 2016 ; Nie et al, 2018 ).…”

Protective Effects and Mechanisms of Dendrobium nobile Lindl. Alkaloids on PC12 Cell Damage Induced by Aβ25-35

“…DNLA was isolated from the extracts and analyzed by LC-MS/MS. Alkaloids accounted for 79.8% of the DNLA and were comprised of 92.6% dendrobine (C16H25O2N), 3.3% dendrobine-N-oxide (C16H25O3N), 2.0% nobilonine (C17H27O3N), 0.9% dendroxine (C17H25O3N), 0.32% 6-hydroxy-nobilonine (C17H27O4N), and 0.07% 13-hydroxy-14-oxodendrobine (C16H23O4N) [ 21 , 24 ]. A β 25–35 was purchased from Sigma (American).…”

“…Neurons were seeded into 96-well plates and treated with DNLA for 30 h at different concentrations. After five replicates were made for each treatment, cell viability was evaluated by MTT assays as previously described [ 24 ]. The cell viability is expressed as an OD percentage of cells with the indicated treatments in cells treated with the DMSO control treatment.…”

“…Since it is sometimes impossible to determine the impact of a drug at a concentration, we used the MTT experiment to determine the cell survival rate to determine the effective range. In this study, we used three concentrations within the effective range to observe whether the drug is dose-dependent [ 22 , 24 ], and the MTT experiment was used to observe the cytotoxicity of A β 25-35 to PC12 cells. The results showed that the cell viability of the MTT experiment in the model group decreased significantly, suggesting A β 25-35 can produce cytotoxicity to PC12 cells and successfully established as the experimental model.…”

Dendorbium Nobile Lindl. Alkaloids Suppress NF-kB and NLRP3 Signaling Pathways to Attenuate Lipopolysaccharideinduced Neuroinflammation

“…is a Chinese medicine for many disorders and Dendrobium Nobile Lindl. alkaloids (DNLA) has been shown to have protective effects against neurodegenerative diseases, such as to reduce the Aβ 25-35 -induced cytotoxicity and axonal degeneration in primary neurons [18,19], attenuate LPS-induced hyperphosphorylation of tau, Aβ-induced neuronal apoptosis and synaptic loss [20,21], reduce the formation and aggregation of toxic amyloid in SD rats [22], and also protect against aging-related learning and memory deficits, neuronal aging and loss in SAMP8 mice [23,24]. In addition, DNLA are effective in alleviating inflammation.…”