Inhibiting c-Jun N-terminal kinase (JNK)-mediated apoptotic signaling pathway in PC12 cells by a polysaccharide (CCP) from Coptis chinensis against Amyloid-β (Aβ)-induced neurotoxicity

• Published in: International journal of biological macromolecules 2019-08, Vol.134, p.565-574
• Main Authors: Li, Yujuan, Wang, Bingmei, Liu, Cong, Zhu, Xiaoting, Zhang, Pengqi, Yu, Hongkui, Li, Yunqiang, Li, Zhuohan, Li, Mingquan
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta-Peptides - toxicity; Animals; Apoptosis; Apoptosis - drug effects; Cell Line; Chemical Phenomena; Coptis - chemistry; Coptis chinensis polysaccharide; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System - drug effects; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Neurons - drug effects; Neurons - metabolism; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacology; Phytochemicals - chemistry; Phytochemicals - pharmacology; Plant Extracts - chemistry; Plant Extracts - pharmacology; Polysaccharides - chemistry; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; Rats
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2019.05.041

In this study, we investigated the protective effect and possible mechanism of a polysaccharide (CCP) from Coptis chinensis against Amyloid-β protein (Aβ)-induced toxicity in PC12 cells. The results showed pretreatment with CCP significantly protected PC12 cells from Aβ25–35 induced cell death, lactate dehydrogenase (LDH) release, nuclear fragmentation, mitochondrial dysfunction and cytochrome c release from mitochondria. Furthermore, CCP (100 μg/ml) significantly inhibited Aβ25–35 induced c-Jun N-terminal kinase (JNK) phosphorylation, but not influence signal-regulated kinase (ERK) and P38 mitogen-activated protein kinase (p38MAPK) pathway, and interestingly, the promoting effect of CCP on PC12 cell survival was only blocked by pre-treatment with a SP600125 (JNK inhibitor). In addition, Aβ25–35-induced increase of Bax and cleaved caspase-3, as well as decrease of Bcl-2 protein expression was markedly reversed by CCP or SP600125. Thus, our results indicate that the neuroprotective effect of CCP is associated with JNK-dependent apoptotic pathway.