Kaempferia parviflora Rhizome Extract Inhibits Glutamate-Induced Toxicity in HT-22 Mouse Hippocampal Neuronal Cells and Extends Longevity in Caenorhabditis elegans

SIMPLE SUMMARY: In aging societies, age-associated diseases are recognized to diminish people’s quality of life. Kaempferia parviflora Wall. ex Baker or “Kra-chai-dam” is a medicinal plant that is known to exhibit numerous pharmacological effects such as anti-inflammation, antimicrobial, and sexual-enhancing activity, and has been used as a nerve tonic. Due to its known neuropharmacological activities, we hypothesize that its rhizome extract might possess both neuroprotective and longevity-enhancing properties. We found that the extract protected glutamate-induced cytotoxicity of mouse hippocampal HT-22 neuronal cells, thus reducing apoptotic cell death. Concomitantly, cells had lower levels of intracellular reactive oxygen species, and changes in the expression of related proteins were found to support the molecular neuroprotection. Furthermore, we found the extract could extend the lifespan of Caenorhabditis elegans. Overall, our study proved that the K. parviflora rhizome extract possessed neuroprotective and longevity-enhancing properties. ABSTRACT: Kaempferia parviflora Wall. ex Baker (KP) or “Kra-chai-dam” has been shown to exhibit several pharmacological effects including anti-inflammation, antimicrobial, and sexual-enhancing activity. The objectives of this study included an investigation of the effect of KP rhizome extract against glutamate-induced toxicity in mouse hippocampal HT-22 neuronal cells, determination of the underlying mechanism of neuroprotection, and an evaluation of the effect of KP extract on the longevity of Caenorhabditis elegans. HT-22 cells were co-treated with glutamate (5 mM) and KP extract (25, 50, and 75 μg/mL) for 14 h. Cell viability, intracellular reactive oxygen species (ROS) assay, fluorescence-activated cell sorting (FACS) analysis, and Western blotting were performed. The longevity effect of KP extract on C. elegans was studied by lifespan measurement. In HT-22 cells, co-treatment of glutamate with KP extract significantly inhibited glutamate-mediated cytotoxicity and decreased intracellular ROS production. Additionally, the glutamate-induced apoptosis and apoptotic-inducing factor (AIF) translocation were blocked by KP extract co-treatment. Western blot analysis also demonstrated that KP extract significantly diminished extracellular signal-regulated kinase (ERK) phosphorylation induced by glutamate, and brain-derived neurotrophic factor (BDNF) was recovered to the control. Moreover, this KP extract treatment prolonged the lifespan of C. elegans. Altogether, this study suggested that KP extract possesses both neuroprotective and longevity-inducing properties, thus serving as a promising candidate for development of innovative health products.