Neuroprotective mechanisms of luteolin in glutamate-induced oxidative stress and autophagy-mediated neuronal cell death

Abstract

Neurodegenerative diseases, characterized by progressive neuronal dysfunction and loss, pose significant health challenges. Glutamate accumulation contributes to neuronal cell death in diseases such as Alzheimer's disease. This study investigates the neuroprotective potential of Albizia lebbeck leaf extract and its major constituent, luteolin, against glutamate-induced hippocampal neuronal cell death. Glutamate-treated HT-22 cells exhibited reduced viability, altered morphology, increased ROS, and apoptosis, which were attenuated by pre-treatment with A. lebbeck extract and luteolin. Luteolin also restored mitochondrial function, decreased mitochondrial superoxide, and preserved mitochondrial morphology. Notably, we first found that luteolin inhibited the excessive process of mitophagy via the inactivation of BNIP3L/NIX and inhibited lysosomal activity. Our study suggests that glutamate-induced autophagy-mediated cell death is attenuated by luteolin via activation of mTORC1. These findings highlight the potential of A. lebbeck as a neuroprotective agent, with luteolin inhibiting glutamate-induced neurotoxicity by regulating autophagy and mitochondrial dynamics.

Luteolin alleviates cadmium-induced metabolism disorder through antioxidant and anti-inflammatory mechanisms in chicken kidney

“…Some edible herbs rich in Lut were used to restore the balance of oxidation and antioxidation system owing to their strong ROS scavenging capacity. According to a recent study, the protective effects of Lut have also been illustrated in the kidney and liver of rats, through anti-inflammatory and antioxidative regulation of the secretion of vital inflammatory cytokines (TNF-α, IL-6, IL-1β), upregulating the antioxidative enzyme catalase ( CAT ) and superoxide dismutase ( SOD ) activities and downregulating the malondialdehyde ( MDA ) concentration ( Vongthip et al, 2024 ). Surprisingly, a previous study indicated that Lut had various biological effects that could impact on hepatic steatosis by inhibiting different degrees of lipogenesis and lipid absorption, and could also be used to treat other metabolic diseases, including non-alcoholic fatty liver, obesity and diabetes disease ( Yao et al, 2023 ).…”