Neuroprotective Effects of Dammarane-Type Saponins from Panax notoginseng on Glutamate-Induced Cell Damage in PC12 Cells
Neuroprotective Effects of Dammarane-Type Saponins from Panax notoginseng on Glutamate-Induced Cell Damage in PC12 Cells
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三七达玛烷型皂苷对谷氨酸诱导的 PC12 细胞损伤的神经保护作用
DOI：
10.1055/a-0853-7754
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发表时间：
2019-02
期刊：
影响因子：
2.7
通讯作者：
Wang Hao
中科院分区：
文献类型：
--
作者：
Zhang Bao Bao;Hu Xiao Long;Wang Yu Yan;Li Jun Yan;Thi Anh Pham;Wang Hao
摘要达玛烷型皂苷是三七的主要活性成分，对不同的神经退行性疾病动物模型具有明显的神经保护作用。然而，由于这些化合物具有不同的结构，因此各个化合物提供的保护水平不同，并且可以基于结构-活性关系来选择高活性化合物。谷氨酸是一种主要的兴奋性神经递质，在突触反应的发展中起着重要的作用。然而，过量的细胞外谷氨酸水平导致中枢神经系统中的神经元功能障碍。在此，我们研究了9种皂苷（化合物1 - 9）在0.1 - 10 μM浓度范围内对谷氨酸处理的PC 12细胞的神经保护作用。 MTT测定显示，与谷氨酸处理的细胞（44.6%）相比，这些化合物将细胞活力分别增加至65.6%、69.8%、76.9%、91.7%、74.4%、63.3%、59.9%、64.7%和59.9%。原人参三醇（化合物4）是最具神经保护性的化合物，随后的实验表明，用化合物4预处理显著逆转线粒体膜电位崩溃，增加超氧化物歧化酶活性，并降低乳酸脱氢酶渗漏、丙二醛水平、活性氧物种产生和细胞凋亡。化合物4还降低Bax/Bcl-2比率，切割半胱天冬酶3、N-甲基-D-天冬氨酸受体1和Ca 2 +-/钙调蛋白依赖性蛋白激酶II表达，并抑制谷氨酸诱导的细胞色素C释放和凋亡信号调节激酶1、c-Jun N-末端激酶和p38的磷酸化。结果表明，原人参三醇具有明显的神经保护作用，可能是一种很有前途的神经保护剂，用于预防和治疗神经退行性疾病。
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.
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影响因子：
16.2
作者：
Garden GA;La Spada AR
通讯作者：
La Spada AR
青藤碱通过 NMDAR1/CAMKII/CREB 途径防止吗啡依赖：星形胶质细胞来源的外泌体的可能作用
DOI：
10.3390/molecules23092370
发表时间：
2018-09-17
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Ou J;Zhou Y;Li C;Chen Z;Li H;Fang M;Zhu C;Huo C;Yung KK;Li J;Luo C;Mo Z
通讯作者：
Mo Z
影响因子：
6.3
作者：
Ghaeminia M;Rajkumar R;Koh HL;Dawe GS;Tan CH
通讯作者：
Tan CH
影响因子：
4.6
作者：
Neal M;Richardson JR
通讯作者：
Richardson JR
影响因子：
2.7
作者：
Zou S;Zhang M;Feng L;Zhou Y;Li L;Ban L
通讯作者：
Ban L