Loliolide combats glutamate-induced neurotoxicity by oxidative stress through MAPK/Nrf2 pathway in hippocampal neuronal cells

Abstract

Neurodegenerative diseases are caused by neurons damage in the brain. Because damaged neurons are difficult to recover, preventing neurons damage may be the most fundamental way to reduce the incidence of the disease. Despite significant efforts to increase understanding of pathogenesis and finding potential treatments in neurodegeneration, there is still no satisfactory treatments for the disease. Excess glutamate generates reactive oxygen species (ROSs) and increases intracellular calcium levels, consequence neuronal dysfunction and cell death, which in turn leads to neurodegeneration. Therefore, the study focused on isolating loliolide from Sargassum horneri and exploring its neuroprotective effect in hippocampal neuronal cells. Loliolide could successfully restore cell viability against glutamate toxicity and reduce apoptosis by inhibiting sub-G1 population. Loliolide attenuated glutamate-induced apoptosis in HT22 cells by upregulating anti-apoptotic (Bcl-2) and downregulating pro-apoptotic (Bax, Caspase3, Caspase9, Cytochrome c, p53, and cleaved PARP) protein expression. Loliolide activates the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway as well as reduced glutamate-induced oxidative stress by inhibiting mitogen-activated protein kinases (MAPKs; ERK, JNK, and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways (IκBα and NF-κB, and p65). Loliolide shows the ability to alleviate oxidative damage by activating the MAPK/Nrf2 signaling pathway in HT22 cells. These findings revealed pharmacological candidates for loliolide in the prevention and/or treatment of neurodegenerative diseases.