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

Hyo Shin Kim, Ji Youn Lim, Dong Geun Sul, Bang Yeon Hwang, Tae J. Won, Kwang Woo Hwang, So Young Park

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Alzheimer's disease is the most common form of dementia, causing progressive cognitive dysfunction, particularly memory loss. Recently, modulation of beta-amyloid (Aβ) 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-1α,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 Aβ-induced toxicity in PC12 cells. Pretreatment with CBNU06 (20 μg/ml) prior to Aβ25-35 (25 μM) 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-κB 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 Aβ on Bax and Bcl-2. Taken together, these results suggest that CBNU06 protected PC12 cells against Aβ-induced neurotoxicity through the inhibition of the NF-κB signaling pathways. Therefore, CBNU06 has the possible beneficial effects in Alzheimer's disease by attenuating Aβ-induced toxicity.

Original languageEnglish
Pages (from-to)25-31
Number of pages7
JournalEuropean Journal of Pharmacology
Volume622
Issue number1-3
DOIs
Publication statusPublished - 2009 Nov 10

Fingerprint

NF-kappa B
Diterpenes
PC12 Cells
Neuroprotective Agents
Amyloid
Alzheimer Disease
Isodon
Trypan Blue
Memory Disorders
Cyclooxygenase 2
Dementia
Cytoplasm
19-hydroxy-1alpha,6-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide
Inhibition (Psychology)
Staining and Labeling

Keywords

  • Alzheimer's disease
  • Beta-amyloid
  • CBNU06 (19-hydroxy-1α,6-diacetoxy-6,7-seco-ent-kaur-16-en-15-one-7,20-olide)
  • NF-kappaB
  • PC12 cells

ASJC Scopus subject areas

  • Pharmacology

Cite this

Neuroprotective effects of the new diterpene, CBNU06 against beta-amyloid-induced toxicity through the inhibition of NF-kappaB signaling pathway in PC12 cells. / Kim, Hyo Shin; Lim, Ji Youn; Sul, Dong Geun; Hwang, Bang Yeon; Won, Tae J.; Hwang, Kwang Woo; Park, So Young.

In: European Journal of Pharmacology, Vol. 622, No. 1-3, 10.11.2009, p. 25-31.

Research output: Contribution to journalArticle

Kim, Hyo Shin ; Lim, Ji Youn ; Sul, Dong Geun ; Hwang, Bang Yeon ; Won, Tae J. ; Hwang, Kwang Woo ; Park, So Young. / Neuroprotective effects of the new diterpene, CBNU06 against beta-amyloid-induced toxicity through the inhibition of NF-kappaB signaling pathway in PC12 cells. In: European Journal of Pharmacology. 2009 ; Vol. 622, No. 1-3. pp. 25-31.
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AU - Won, Tae J.

AU - Hwang, Kwang Woo

AU - Park, So Young

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