Mangifera indica ‘Namdokmai’ Prevents Neuronal Cells from Amyloid Peptide Toxicity and Inhibits BACE-1 Activities in a Drosophila Model of Alzheimer’s Amyloidosis

Abstract

Alzheimer’s disease (AD) is a progressive neurological illness with few effective treatments. Thus, ameliorating the effects of AD using natural products has attracted global attention with promising efficacy and safety. In this study, ten tropical fruits including Ananas comosus ‘Phulae’, Ananas comosus ‘Pattavia’, Carica papaya ‘Khaekdum’, Carica papaya ‘Khaeknuan’, Durio zibethinus ‘Monthong’, Durio zibethinus ‘Chanee’, Psidium guajava ‘Kimju’, Psidium guajava ‘Keenok’, Mangifera indica ‘Kaew’ and Mangifera indica ‘Namdokmai’ were screened for their inhibitory activities against the key enzymes, cholinesterases and β-secretase (BACE-1), involved in AD pathogenesis. The top three fruit extracts with promising in vitro anti-AD activities were further investigated using rat pheochromocytoma PC-12 neuronal cell line and Drosophila AD model. Data showed that M. indica ‘Kaew’, M. indica ‘Namdokmai’ and P. guajava ‘Kimju’ reduced Aβ1–42-mediated neurotoxicity by promoting glutathione-dependent enzymes, while M. indica ‘Namdokmai’ limited Aβ1–42 peptide formation via BACE-1 inhibition and amended locomotory behavior of the Drosophila AD model. Results indicated the potential anti-AD properties of tropical fruits, particularly M. indica ‘Namdokmai’ in the prevention of Aβ1–42-mediated neurotoxicity and as a BACE-1 blocker.

Phenolic content of Thai Bao mango peel and its in-vitro antioxidant, anti-cholinesterase, and antidiabetic activities

“…indica ‘Namdokmai’ showed superior inhibition properties against AChE, BACE-1, and BChE. In the same study, anti-AD properties in the Drosophila model showed a significant reduction of BACE-1 in the brains of AD flies (6.03 U/mL) by 250 µg/mL of M. indica 'Namdokmai' extract ( Temviriyanukul et al, 2022 ). The present results indicated that Bao MPE showed higher inhibitory activity against enzymes involved in AD compared to the above-reported mango variety from Thailand.…”

“…Inhibition of cholinesterases (butyrylcholinesterase (BChE) and acetylcholinesterase (AChE)) that degrade neurotransmitters is crucial ( Moussa-Pacha et al, 2020 , Rajput et al, 2020a ). Phytochemicals from mango and its byproducts have been reported to have inhibitory potential for activities against neurotransmitters, acetylcholine, and degrading enzymes, AChE and BchE ( Temviriyanukul et al, 2022 ). However, compared to donepezil, which acts as a competitive cholinesterase inhibitor, the inhibitory potentials of mango peel extract were 2.6–44.0-fold higher, suggesting lower inhibitory strength against these enzymes.…”

“…This inhibitory potential of the MPE could be due to the abundance of mangiferin in the extract. Temviriyanukul et al (2022) examined the potential AD-associated enzyme inhibition by different varieties of M . indica (Namdokmai, Kimju, and Keaw in Thailand) and found that the 0.25 mg/mL concentration showed strong AChE and BChE inhibition (69–83 % and 70–84 %, respectively), among which M .…”

Optimized Conditions for the Extraction of Phenolic Compounds from Aeginetia indica L. and Its Potential Biological Applications

“…AChE: acetylcholinesterase; BChE: butyrylcholinesterase; BACE-1: β-secretase; DPP-IV: dipeptidyl peptidase-IV; IC 50 : half maximal inhibitory concentration; ND: not detected. Information on the positive controls was received from * Chupeerach et al, 2022 [ 20 ], $ Promyos et al, 2020 [ 21 ], and # Temviriyanukul et al, 2022 [ 22 ].…”