3',4'-Didemethylnobiletin will induces stage II detoxification gene expression in PC12 cells

Su JD, Yen JH, Li S, Weng CY, Lin MH, Ho CT, Wu MJ. "Free Radic Biol Med. 2011 Oct "

The pharmacological inhibitor SP600125 may be largely employed as being a c-JUN N-terminal kinase (JNK1/2) inhibitor. In this study, we evaluated whether pretreatment with SP600125 was able to prevent Orthopoxviruses Vaccinia virus (VACV), Cowpox virus (CPXV) and modified Vaccinia virus Ankara (MVA) replication.

Furthermore, we investigated the cytoprotective results and mechanisms in the citrus flavonoid nobiletin (NOB) and its metabolite, 3',4'-didemethylnobiletin (3',4'-dihydroxy-5,6,7,8-tetramethoxyflavone; DTF), in PC12 cells. Both NOB and DTF exhibited strong potency in attenuating serum withdrawal- and H(2)O(2)-caused cell death and increased intracellular GSH degree via upregulation of each catalytic and modifier subunits of glutamate-cysteine ligase (GCL).

However, only DTF suppressed intracellular ROS accumulation in H(2)O(2)-treated cells, induced heme oxygenase-1 (HO-1) expression, and enhanced nuclear element E2-related issue 2 (Nrf2) binding towards the ARE.

Nevertheless, DTF-mediated HO-1 upregulation was impartial of Nrf2 activation simply because knockdown of Nrf2 expression by siRNA didn't have an effect onassociatedbrought on cytotoxicity and also the last substantially attenuated NOB- and DTF-mediated antiapoptotic steps, indicating the involvement of PI3K/Akt signaling within their cytoprotective results.

In summary, HO-1 and GCL upregulation and intrinsic ROS-scavenging activity could contribute to DTF-mediated cytoprotection. Furthermore, modulation of PI3K/Akt signaling is involved in channeling the DTF stimulus for cell survival from oxidative insults.