Component Analysis of Dendrobium nobile Lindl. Alkaloids and its Inhibitory Effect on the Apoptosis of PC12 Cell Induced by Aβ1-42
ZHANG Cheng-chen1,2, WU Qin1, SHI Jing-shan1*, LU Yan-liu1
1. Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Zunyi Medical University, Zunyi 563000, China; 2. State Key Laberatory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China
Abstract：OBJECTIVE To investigate the neuroprotective effect of Dendrobium nobile Lindl. alkaloids (DNLA) on Aβ1-42-induced PC12 cell damage and explored its underlying molecular mechanism. METHODS The stems of Dendrobium nobile Lindl. were extracted with 95% ethanol, dissolved in acidic water, extracted with petroleum ether to remove impurities, then isolated using cation exchange resin column chromatography and Sephadex LH-20 gel column chromatography to obtain DNLA; the constituents of DNLA were analyzed using UPLC-ESI-HRMS technology. PC12 cells were divided into seven groups:control group; 0.03, 0.3, 3.0 μg·mL-1 DNLA group, 30 μmol·L-1 Aβ1-42 model group, DNLA low-concentration group (Aβ1-42+0.03 μg·mL-1 DNLA); DNLA medium-concentration group (Aβ1-42+0.3 μg·mL-1 DNLA), DNLA high-concentration group (Aβ1-42+3 μg·mL-1 DNLA), and a positive control group (Aβ1-42+10 μmol·L-1 memantine). The protective effect of DNLA on Aβ1-42-induced PC12 cell cytotoxicity was investigated and the regulation effect of DNLA on CaMKK2 phosphorylation and the expression of caspase-3 and cleaved caspase-3 were explored. RESULTS The alkaloids from D. nobile were mainly dendrobine, dendramine, dendrobine N-oxide, and dendroxine. Relative to the model group, the 0.3 and 3.0μg·mL-1 DNLA groups showed significant inhibition of cell cytotoxicity, less damage to cell morphology, fewer apoptotic cells, and downregulation of CaMKK2 (Ser511) phosphorylation, caspase-3, and cleaved caspase-3 protein expression levels in Aβ1-42-treated PC12 cells(P<0.05, P<0.01). CONCLUSION DNLA inhibites Aβ1-42-induced PC12 cell apoptosis, and the mechanism may be related to negative-regulating CaMKK2 (Ser511) phosphorylation, downregulating caspase-3 protein expression, and reducing caspase-3 activation.
张成宸, 吴芹, 石京山, 鲁艳柳. 金钗石斛生物碱成分分析及其对Aβ1-42所致PC12细胞凋亡的抑制作用[J]. 中国药学杂志, 2021, 56(13): 1059-1067.
ZHANG Cheng-chen, WU Qin, SHI Jing-shan, LU Yan-liu. Component Analysis of Dendrobium nobile Lindl. Alkaloids and its Inhibitory Effect on the Apoptosis of PC12 Cell Induced by Aβ1-42. Chinese Pharmaceutical Journal, 2021, 56(13): 1059-1067.
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2021, Vol. 56 
