250: Anti-Neurodegeneration and Potential Contributors of Gac Fruit Using a HT-22 Cell Model

Introduction

Physical and psychological stresses in our daily life contribute to neurodegenerative diseases. Currently, it has become a serious mental health problem worldwide. Chronic and repeated acute stress increases the release of stress hormones which initiate beta-amyloid (Aβ) creation and form Aβ plaques. Aβ causes mitochondrial dysfunction, oxidative stress, and synaptic dysfunction, which leads to neurodegenerative disease. Recent studies have shown that Gac fruit (Momordica cochinchinensis) can induce neurite outgrowth, show anti-memory impairment activity, and enhance Aβ1-42 clearance. However, the anti-neurodegenerative effect of fresh gac fruit and its relative cellular mechanism is still unknown.

Methods

In this study, we obtained different fresh gac fruit parts (peel, pulp, aril, and seed) and extracted with different polar solvents including, water, 80% ethanol, ethyl acetate, and n-hexane. To investigate the neuroprotective effect against the Aβ-induced cytotoxicity and synaptic dysfunction by evaluating the synaptic related mRNA expression including, postsynaptic density-95 (PSD-95), neurexin 2, and neurexin 3.

Results

Results showed that gac fruit peel 80% ethanol extract (PE-EtOH) and seed ethyl acetate extract (SE-EtOAc) protected Aβ-induced cytotoxicity than the other extracts. Both PE-EtOH and SE-EtOAc showed neuroprotective effects by protecting the cell viability (%) and morphology damage, reducing the intracellular reactive oxygen species (ROS) production, and protecting mitochondrial dysfunction against Aβ exposure in the HT-22 cell model. Furthermore, PE-EtOH and SE-EtOAc protected synaptic function by normalizing the Aβ-induced significant change in synaptic related mRNA expression. PE-EtOH treatment increased the PSD-95 and reduced the neurexin 2 levels against Aβ exposure, without affecting the neurexin 3. However, SE-EtOAc increased the PSD-95, neurexin 3 levels, and reduced the neurexin 2 expressions.

Significance

These results demonstrated that, PE-EtOH treatment targeted the PSD-95 and neurexin 2, while the SE-EtOAc affected a broader category of synaptic proteins to protect the synaptic function. In conclusion, this study showed the anti-neurodegenerative effect of gac fruit, suggesting that gac fruit could be an interesting natural source for protecting against neurodegenerative disorders. Further studies are needed to know the main contributors in gac fruit and their related mechanisms.

Authors: Asif Ali1, Chin-Kun Wang1