Reactive oxygen species, derived from hypoxia and reoxygenation during transient focal cerebral ischemia (tFCI), are associated with the signaling pathway that leads to neuronal survival or death, depending on the severity and duration of the ischemic insult. The Akt survival signaling pathway is regulated by oxidative stress and is implicated in activation of nuclear factor-κB(NF-κB). Mild cerebral ischemia in mice was used to induce increased levels of Akt phosphorylation in the cortex and striatum. To clarify the role of Akt activation by NF-κB after tFCI, we injected the specific Akt inhibitor IV that inhibits Akt phosphorylation/activation. Inhibition of Akt phosphorylation induced decreases in sequential NF-κB signaling after 30 mins of tFCI at 1 h. Furthermore, the downstream survival signals of the Akt pathway were also decreased. Akt inhibitor IV increased ischemic infarct volume and apoptotic-related DNA fragmentation. Superoxide production in the ischemic brains of mice pretreated with the Akt inhibitor was higher than in vehicle-treated mice. In addition, those pretreated mice showed a reduction of approximately 33% in copper/zinc-superoxide dismutase expression. We propose that Akt signaling exerts its neuroprotective role by NF-κB activation in oxidative cerebral ischemia in mice.

Caffeic acid phenethyl ester (CAPE) is an active ingredient of beehive propolis with a structure similar to phenolic acid. The estrogenic effects of propolis were previously demonstrated through the activation of an estrogen receptor. To identify the estrogenic properties of propolis, CAPE was evaluated using in vitro and in vivo methods. CAPE showed selective binding affinity to human estrogen receptor β (hERβ) rather than hERα. CAPE also reduced ERα expression in MCF‐7 and MDA 231 cells. In the yeast estrogen receptor transcription assay, CAPE produced the transcriptional activity of estrogen‐responsive element with EC₅₀ values of 3.72 × 10⁻⁶ M. CAPE did not increase the growth of MCF‐7 estrogen receptor‐positive breast cancer cells in doses ranging from 10⁻⁷ to 10⁻⁵ M. In order to understand how CAPE acts in animals, CAPE was tested by a uterotrophic bioassay. Treatment with CAPE (100, 500 mg/kg) did not increase the uterine weight relative to 3 μg/kg 17β‐estradiol treatment. The results indicate that CAPE, which is a selective agonist to hERβ, but does not show any estrogenic effect on estrogen receptor‐positive breast cancer cells and in immature rat uterine tissue, is a potential selective estrogen receptor modulator. Copyright © 2009 John Wiley & Sons, Ltd.

Kim S, et al. Exp Neurobiol. 2017 Aug;26(4):227-239. https://doi.org/10.5607/en.2017.26.4.227

Oxidative stress after stroke is associated with the inflammatory system activation in the brain. The complement cascade, especially the degradation products of complement component 3, is a key inflammatory mediator of cerebral ischemia. We have shown that pro‐inflammatory complement component 3 is increased by oxidative stress after ischemic stroke in mice using DNA array. In this study, we investigated whether up‐regulation of complement component 3 is directly related to oxidative stress after transient focal cerebral ischemia in mice and oxygen‐glucose deprivation in brain cells. Persistent up‐regulation of complement component 3 expression was reduced in copper/zinc‐superoxide dismutase transgenic mice, and manganese‐superoxide dismutase knock‐out mice showed highly increased complement component 3 levels after transient focal cerebral ischemia. Antioxidant N‐tert‐butyl‐α‐phenylnitrone treatment suppressed complement component 3 expression after transient focal cerebral ischemia. Accumulation of complement component 3 in neurons and microglia was decreased by N‐tert‐butyl‐α‐phenylnitrone, which reduced infarct volume and impaired neurological deficiency after cerebral ischemia and reperfusion in mice. Small interfering RNA specific for complement component 3 transfection showed a significant increase in brain cells viability after oxygen‐glucose deprivation. Our study suggests that the neuroprotective effect of antioxidants through complement component 3 suppression is a new strategy for potential therapeutic approaches in stroke.

Minha Kim, So-Dam Kim, Kyoung In Kim, Eun Hae Jeon, Min Gee Kim, Yu-Ree Lim, Enkhmaa Lkhagva-Yondon, Yena Oh, Kwangmin Na, Young Cheul Chung, Byung Kwan Jin, Yun Seon Song and Myung-Shin Jeon. Exp Neurobiol 2021;30:155-69. https://doi.org/10.5607/en20062