Neuroprotective effects of the new diterpene, CBNU06 against beta-amyloid-induced toxicity through the inhibition of NF-kappaB signaling pathway in PC12 cells.
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.
Kim
Hyo-Shin
HS
Department of Immunology, College of Pharmacy, Research Institute for Translational System Biomics, Chung-Ang University, Seoul, Korea.
Lim
Ji-Youn
JY
Sul
Donggeun
D
Hwang
Bang Yeon
BY
Won
Tae-Jun
TJ
Hwang
Kwang Woo
KW
Park
So-Young
SY
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000172:deficiency / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
C547088:19-hydroxy-1alpha,6-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide; D016229:Amyloid beta-Peptides; D004224:Diterpenes; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D051546:Cyclooxygenase 2