Terminalia chebula: A Promising Indigenous Phytotherapeutics for Alzheimer’s Disease

Introduction: Alzheimer’s disease (AD) is a progressive neurologic disorder that leads to the irreversible loss of neurons. Amyloid plaques and loss of cholinergic neurons are two main characteristics of AD. In AD, the action of neurotransmitter, acetylcholine, is terminated by acetylcholinesterase (AChE) present in the synaptic cleft, and formation of amyloid plaques in the synapse prevents acetylcholine to reach their receptors on the postsynaptic neurons. Over the years, scientists have discovered various classes of the molecules for treatment of the disease and some are derived from plants such as rivastigmine, huperzine, and galantamine. Numerous plants are being used traditionally as treatment for neurodegenerative diseases such as AD, anti‑aging, and preventing dementia. Among these indigenous plants, Terminalia chebula (Tc) is regarded to slow down the aging process and to improve the cognition in the traditional age‑old practices. Objective: In this study, we have assayed the methanolic extract of Tc leaves to assess its inhibitory effect on four different pathways related to AD. Materials and Methods: Ellman method was used to measure the effect of Tc on AChE activity. To assess the effect of Tc on amyloid‑β (Aβ)‑secretion pathway, we measured the amount of Aβ40 in cell culture medium using ELISA Kit. Aβ‑aggregation (40 and 42) and disruption of Aβ‑aggregates (40 and 42) were monitored using a fluorescence technique, Thioflavin‑T, in vitro. Results: Our results show that Tc has significant inhibitory effect on all the above‑mentioned assays, with the best IC50 = 10.3 µg/ml for Aβ40‑aggregation followed by Aβ42‑aggregation (IC50 = 18.6 µg/ml), disruption of Aβ40‑aggregates (IC50 = 41.8 µg/ml), disruption of Aβ42‑aggregates (IC50 = 132.2 µg/ml), and AChE activity (IC50 = 200 µg/ml). Besides, it showed 21.46% inhibition on Aβ40 level in HEK293 cell line.