PMID: Eur J Pharmacol. 2018 Sep 5 ;834:295-304. Epub 2018 Jul 27. PMID: 30059683 Abstract Title: Morroniside prevents HOor Aβ-induced apoptosis via attenuating JNK and p38 MAPK phosphorylation. Abstract: Amyloid-β peptide (Aβ) plays a causal role in the development and progression of Alzheimer's disease (AD). Oxidative stress and activation of mitogen-activated protein kinase (MAPK) are involved in Aβ-induced neurotoxicity. Morroniside, one active monomer of dry ripe sarcocarp of Cornus officinalis, hasshown antioxidant properties in several cell lines. The present study investigated the protective actions of morroniside against the cytotoxicity produced by exposure to HOor Aβin rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to 150 μM HOor 20 μM Aβdown-regulated anti-apoptotic protein expression (Bcl-2), up-regulated pro-apoptotic protein expression (Bax, cytochrome C, and cleaved caspase-3), increased JNK and p38 MAPK phosphorylation and finally caused significant cell death. This effect was reversed by pretreatment with morroniside in a dose-dependent manner. Among the selective inhibitors of MAPKs, the JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) showed steady preventive effect against HOor Aβ-induced apoptosis. The results suggest that different from the selective inhibitors of MAPKs, morroniside can inhibit HOor Aβ-induced apoptotic pathway activation through suppressing its upstream signaling components of JNK and p38 MAPK phosphorylation simultaneously.
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