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DOI: 10.1055/a-0853-7754
Neuroprotective Effects of Dammarane-Type Saponins from Panax notoginseng on Glutamate-Induced Cell Damage in PC12 Cells
Publication History
received 05 November 2018
revised 20 January 2019
accepted 03 February 2019
Publication Date:
21 February 2019 (online)
![](https://www.thieme-connect.de/media/plantamedica/20190910/lookinside/thumbnails/10-1055-a-0853-7754_pmc0843-1.jpg)
Abstract
Dammarane-type saponins, the main active ingredients of Panax notoginseng, have substantial neuroprotective effects in different animal models of neurodegenerative diseases. However, because these compounds have different structures, the level of protection provided by individual compounds varies, and highly active compounds can be selected based on structure-activity relationships. Glutamate is a major excitatory neurotransmitter that plays an important role in synaptic response development. However, excessive extracellular glutamate levels lead to neuronal dysfunctions in the central nervous system. Herein, we investigated the neuroprotective effects of nine saponins (compounds 1 – 9) on glutamate-treated PC12 cells in the concentration range of 0.1 – 10 µM. The MTT assay revealed that these compounds increased cell viability to 65.6, 69.8, 76.9, 91.7, 74.4, 63.3, 59.9, 64.7, and 59.9%, respectively, compared with the glutamate-treated cells (44.6%). Protopanaxatriol (compound 4) was the most neuroprotective compound, and subsequent experiments revealed that pretreatment with compound 4 significantly reverses mitochondrial membrane potential collapse, increases superoxide dismutase activity, and decreases lactate dehydrogenase leakage, malondiadehyde levels, reactive oxygen species generation, and cell apoptosis. Compound 4 also decreased the Bax/Bcl-2 ratio, cleaved caspase-3, N-methyl-D-aspartic receptor 1, and Ca2+-/calmodulin-dependent protein kinase II expression, and inhibited glutamate-induced cytochrome C release and phosphorylation of apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38. Overall, the results indicate that protopanaxatriol has significant neuroprotective effects, and might be a promising neuroprotective agent for preventing and treating neurodegenerative diseases.
Key words
Panax notoginseng - Araliaceae - neurodegenerative diseases - glutamate - PC12 cells - protopanaxatriolSupporting Information
- Supporting Information
MS, 1H-, and 13C-NMR spectra of compounds 1 – 9 are shown in Supporting Information.
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