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NEUROPROTECTIVE EFFECT OF TERMINALIA CHEBULA EXTRACTS AND ELLAGIC ACID IN PC12 CELLS Shen, Yuh-Chiang; Juan, Chi-Wen; Lin, Che-San; Chen, Chien-Chih & Chang, Chia-Lin Abstract Background: Alzheimer’s disease (AD) is one of the common neurodegenerative disorders among elderly. The purpose of this study was to determine the neuroprotective effect and mechanisms of action underlying the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Aβ25-35)-induced cell toxicity in an undifferentiated pheochromocytoma (PC12) cell line. Materials and Methods: The T. chebula extracts were prepared using the methanol, water, and 95% ethanol. Specifically, the ellagic acid was obtained in our laboratory. Assays including cell toxicity and changes in intracellular reactive oxygen species (ROS) and calcium level were evaluated to examine the neuroprotective effects and mechanisms of the T. chebula extracts and ellagic acid. Results: The methanolic and water extracts of T. chebula and ellagic acid exhibited the strongest neuroprotective activity against Aβ25-35-induced PC12 cell damages at 0.5–5.0 µg/ml. The ellagic acid also exhibited partial neuroprotective activity against H2O2-induced PC12 cell damages at 0.5–5.0 µg/ml. The methanolic and water extracts of T. chebula and ellagic acid protected PC12 cells from Aβ25-35-mediated cell damages and enhanced cell viability thorough two key mechanisms by: (1) inhibiting ROS production and (2) reducing calcium ion influx. Conclusion: The T. chebula represents a promising plant-source as medicine in the application for the treatment of AD. Further investigation focusing on the active component of T. chebula extracts e.g., ellagic acid is crucial to verify the neuroprotective efficacy and mechanisms in vivo. Keywords Neuroprotective effect; Terminalia chebula; ellagic acid; beta-amyloid

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