Neuroprotective potential of flavonoid rich Ascophyllum nodosum (FRAN) fraction from the brown seaweed on an Aβ42 induced Alzheimer's model of Drosophila

Brijesh Singh Chauhan; Rohit Kumar; Pradeep Kumar; Prabhat Kumar; Saket Sinha; Sunil Kumar Mishra; Pradeep Kumar; Kavindra Nath Tiwari; Alan T Critchley; Balakrishnan Prithiviraj; Saripella Srikrishna

doi:10.1016/j.phymed.2021.153872

Neuroprotective potential of flavonoid rich Ascophyllum nodosum (FRAN) fraction from the brown seaweed on an Aβ₄₂ induced Alzheimer's model of Drosophila

Phytomedicine. 2022 Jan:95:153872. doi: 10.1016/j.phymed.2021.153872. Epub 2021 Dec 2.

Affiliations

¹ Cell and Neurobiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
² Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, India.
³ Department of Botany, MMV, Banaras Hindu University, Varanasi 221005, India.
⁴ Verschuren Centre for Sustainability in Energy and the Environment, Cape Breton University, Sydney, Nova Scotia, B1P 6L2 Canada.
⁵ Department of Plant, Food and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, Nova Scotia, B2N 5E3 Canada.
⁶ Cell and Neurobiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India. Electronic address: skrishna@bhu.ac.in.

PMID: 34906893
DOI: 10.1016/j.phymed.2021.153872

Abstract

Background: In Alzheimer Disease (AD) pathogenesis, aggregation of Aβ₄₂ fibrils strongly correlates with memory dysfunction and neurotoxicity. Till date, no promising cures for AD. Report shows that flavonoids contributed anti-oxidant, anti-cancer and neuroprotection activity by regulating the mitochondrial machinery. Here, we first report the identification of flavonoids from Ascophyllum nodosum as having the ability to dissolve Aβ₄₂ fibrils in an AD model of Drosophila. FRAN could be superior anti-AD agents for neuroprotection, their underlying mechanism and how they collectively halted amyloidogenesis is currently being investigated.

Purpose: This study aimed to investigate the neuroprotective role of FRAN in the Aβ₄₂ expressing AD model of Drosophila.

Methods: Drosophila stocks: OregonR⁺, ey-GAL4/CyO, elav^c155-GAL4, UAS-mitoGFP, UAS-mcherry.mito.OMM, UAS-Aβ₄₂/CyO were used, cultured at 28±1 °C in a BOD incubator. Ascophyllum extract rich in flavonoids as revealed by LC-MS study and employed against the AD flies. The validation of Aβ₄₂ expression was done by immunostaining and q-RT PCR. The eye roughness of AD flies was scored in a dose-dependent manner. Further, In vivo and in silico studies of FRAN extract was executed against Aβ₄₂ induced neurotoxicity.

Results: In order to determine the most effective lethal dose of FRAN extract concentration 1, 2, 5, 10 mg/ml were screened using OregonR⁺flies. Extract 1 and 2 mg/ml did not show any lethality. Hence, extract 2 mg/ml was employed on AD flies and a ≥ 50% rescue in the eye phenotype was observed using SEM images. This dose had a strong effect on cell apoptosis, viability, longevity, mitochondrial dysfunction and oxidative stress by regulating mitochondrial dynamic markers in comparable to control. Extract also scavenging free radicals in order to maintain in situ cellular ROS and prevent Aβ₄₂-induced neurotoxicity in vivo and in silico. Hence, we suggest its great potential as a future therapeutic agent for AD treatment.

Conclusion: In conclusion, FRAN extract rich in flavonoids as having largest neuroprotective activity against Aβ₄₂ aggregation in eye tissue of Drosophila. Extract shows strong effect against Aβ₄₂-induced neurotoxicity by altering the various cellular and molecular events. So, it could be considered as strong anti-AD agents for neuroprotection.

Keywords: Alzheimer's disease; Drosophila melanogaster; Flavonoid-rich ascophyllum nodosum; Mitochondrial; Oxidative stress.

MeSH terms

Alzheimer Disease* / drug therapy
Amyloid beta-Peptides
Animals
Ascophyllum*
Disease Models, Animal
Drosophila
Drosophila melanogaster
Flavonoids / pharmacology
Neuroprotection
Peptide Fragments
Seaweed*

Substances

Amyloid beta-Peptides
Flavonoids
Peptide Fragments