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Neuroprotective effects of the new diterpene, CBNU06 against beta-amyloid-induced toxicity through the inhibition of NF-kappaB signaling pathway in PC12 cells.

Authors: Kim, HS  Lim, JY  Sul, D  Hwang, BY  Won, TJ  Hwang, KW  Park, SY 
Citation: Kim HS, etal., Eur J Pharmacol. 2009 Nov 10;622(1-3):25-31. doi: 10.1016/j.ejphar.2009.09.007. Epub 2009 Sep 16.
Pubmed: (View Article at PubMed) PMID:19765580
DOI: Full-text: DOI:10.1016/j.ejphar.2009.09.007

Alzheimer's disease is the most common form of dementia, causing progressive cognitive dysfunction, particularly memory loss. Recently, modulation of beta-amyloid (Abeta) toxicity, one of the major potential causes of Alzheimer's disease, has emerged as a possible therapeutic approach to control the onset of Alzheimer's disease. In this study, we investigated the neuroprotective effects and possible mechanisms by which 19-hydroxy-1alpha,6-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide (named as CBNU06), a new diterpene isolated from Isodon japonicus, acts against Abeta-induced toxicity in PC12 cells. Pretreatment with CBNU06 (20 microg/ml) prior to Abeta(25)(-35) (25 microM) significantly increased the viability of PC12 cells in a dose-dependent manner when examined by Hoechst staining, MTT assay and Trypan blue exclusion assay. This protective effect was accompanied by the decrease in translocation of NF-kappaB p50 and p65 from the cytoplasm to the nucleus, and followed by the decrease in cyclooxygenase-2 (COX-2) levels. In addition, pretreatment with CBNU06 significantly reversed the effect of Abeta on Bax and Bcl-2. Taken together, these results suggest that CBNU06 protected PC12 cells against Abeta-induced neurotoxicity through the inhibition of the NF-kappaB signaling pathways. Therefore, CBNU06 has the possible beneficial effects in Alzheimer's disease by attenuating Abeta-induced toxicity.

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CRRD Object Information
CRRD ID: 10045660
Created: 2015-06-15
Species: All species
Last Modified: 2015-06-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.