Antiaggregation Potential of Padina gymnospora against the Toxic Alzheimer’s Beta-Amyloid Peptide 25–35 and Cholinesterase Inhibitory Property of Its Bioactive Compounds

Abstract

Inhibition of β-amyloid (Aβ) aggregation in the cerebral cortex of the brain is a promising therapeutic and defensive strategy in identification of disease modifying agents for Alzheimer’s disease (AD). Since natural products are considered as the current alternative trend for the discovery of AD drugs, the present study aims at the evaluation of anti-amyloidogenic potential of the marine seaweed Padina gymnospora. Prevention of aggregation and disaggregation of the mature fibril formation of Aβ 25–35 by acetone extracts of P. gymnospora (ACTPG) was evaluated in two phases by Thioflavin T assay. The results were further confirmed by confocal laser scanning microscopy (CLSM) analysis and Fourier transform infrared (FTIR) spectroscopic analysis. The results of antiaggregation and disaggregation assay showed that the increase in fluorescence intensity of aggregated Aβ and the co-treatment of ACTPG (250 μg/ml) with Aβ 25–35, an extensive decrease in the fluorescence intensity was observed in both phases, which suggests that ACTPG prevents the oligomers formation and disaggregation of mature fibrils. In addition, ACTPG was subjected to column chromatography and the bioactivity was screened based on the cholinesterase inhibitory activity. Finally, the active fraction was subjected to LC-MS/MS analysis for the identification of bioactive compounds. Overall, the results suggest that the bioactive compound alpha bisabolol present in the alga might be responsible for the observed cholinesterase inhibition with the IC50 value < 10 μg/ml for both AChE and BuChE when compared to standard drug donepezil (IC50 value < 6 μg/ml) and support its use for the treatment of neurological disorders.

Aqueous–ethanol extracts of some South African seaweeds inhibit beta‐amyloid aggregation, cholinesterases, and beta‐secretase activities in vitro

“…This implies that the seaweed extracts contain some bioactive principles capable of resisting the continuous aggregation of Aβ 1‐42. This result also correlates with the report of Shanmuganathan et al () which established that Padina gymnospora exerted marked inhibitory effects against aggregation of Aβ 25‐35 . Furthermore, the effect of ECK, GLD, GCL, and ULT were also tested on preformed Aβ 1‐42 fibrils to determine their disaggregation potentials.…”

“…In a study conducted by Nisha and Devi (2017), the authors demonstrated that a red alga (Gelidellia acerosa) inhibited BACE-1 activity and subsequently suppressed generation of β-amyloid peptide in the brain of Swiss mice. Some other algal species such as Ecklonia stolonifera (Oh, Choi, & Nam, 2018) and Padina gymnospora (Shanmuganathan, Malar, Sathya, & Dev, 2015) have also been identified as potent BACE-1 inhibitors. This suggests that some biologically active compounds in marine algae may be good sources of BACE-1 inhibitors.…”

Seaweeds: A resource for marine bionanotechnology

“…Fucoxanthin isolated from brown seaweeds proved to have anticancer activity even at lower concentration [85]. Ethanolic extract of most of the seaweeds have therapeutic value, specifically it acts as inhibitor of amyloid-β aggregation seen in Alzheimer's disease [86].…”

Phytol-loaded PLGA nanoparticle as a modulator of Alzheimer’s toxic Aβ peptide aggregation and fibrillation associated with impaired neuronal cell function

“…The anti-aggregation and disaggregation property of phytol and encapsulated phytol were evaluated against the amyloidogenic activity of Ab peptide in two different phases described by previous reports [1]. The effect of phytol and encapsulated phytol on the aggregation pattern of Ab peptide was assessed in phase I; parallely, the disaggregation of mature Ab fibrils by phytol and encapsulated phytol was verified in phase II.…”

“…The major neuropathological hallmark of AD comprises formation of senile plaques and neurofibrillary tangles. The plaques are extracellular deposits mainly composed of fibrillar beta-amyloid (Ab) peptide, which are possibly linked to the modulation of synaptic activity of aging brain [1]. In addition, intracellular fibrillar aggregates of the microtubule-associated protein tau, which is also called as neurofibrillary tangles exhibit hyper-phosphorylation in AD cases [2].…”