CDDO-Me Distinctly Regulates Regional Specific Astroglial Responses to Status Epilepticus via ERK1/2-Nrf2, PTEN-PI3K-AKT and NFκB Signaling Pathways

Abstract

2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid. CDDO-Me shows anti-inflammatory and neuroprotective effects. Furthermore, CDDO-Me has antioxidant properties, since it activates nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a key player of redox homeostasis. In the present study, we evaluated whether CDDO-Me affects astroglial responses to status epilepticus (SE, a prolonged seizure activity) in the rat hippocampus in order to understand the underlying mechanisms of reactive astrogliosis and astroglial apoptosis. Under physiological conditions, CDDO-Me increased Nrf2 expression in the hippocampus without altering activities (phosphorylations) of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphatidylinositol-3-kinase (PI3K), and AKT. CDDO-Me did not affect seizure activity in response to pilocarpine. However, CDDO-Me ameliorated reduced astroglial Nrf2 expression in the CA1 region and the molecular layer of the dentate gyrus (ML), and attenuated reactive astrogliosis and ML astroglial apoptosis following SE. In CA1 astrocytes, CDDO-Me inhibited the PI3K/AKT pathway by activating PTEN. In contrast, CDDO-ME resulted in extracellular signal-related kinases 1/2 (ERK1/2)-mediated Nrf2 upregulation in ML astrocytes. Furthermore, CDDO-Me decreased nuclear factor-κB (NFκB) phosphorylation in both CA1 and ML astrocytes. Therefore, our findings suggest that CDDO-Me may attenuate SE-induced reactive astrogliosis and astroglial apoptosis via regulation of ERK1/2-Nrf2, PTEN-PI3K-AKT, and NFκB signaling pathways.

Process Intensification for Sustainable Microwave-Assisted Bio p-Cymene Production from Limonene

“…Further, concerning polymers, the main compounds detected by GC–MS in these experiments were kaur-16-ene (a), podocarpa-6,13-diene, 13-isopropyl (b), and A-D-neooleana-12,14-diene (c) (Figure ). In this context, the potential biological activity of these high-molecular-weight terpenes is remarkable; they can be used as anticancer, anti-inflammatory, antimelanogenic, and antioxidant agents, as well as in neuroprotection, cytotoxicity, and allelopathy. − …”

“…As mentioned, considering the wide applicability of the isomerization, disproportionation, and polymerization products, for instance, for use as fuel, in extraction, or as bioactive compounds, − these substances are considered useful products and therefore excluded from the “waste” in the E -factor on the basis of the work of Gude and Martinez-Guerra …”