Abstract
Background: The various herbal remedies have been used in Ayurveda which symbolizes traditional medicine system since ancient times. The increasing popularity of herbal medicines has prompted us toward the development of natural therapeutics for preventing neurodegenerative disease such as Alzheimer's disease (AD) in living organisms. This study focused on a flavonoid compound 5,7-dihydroxy-4-methoxyflavone (DMF) also known as acacetin which is a major constituent of Premna odorata (L.) plant. This bioactive flavonoid exhibits several medicinal properties such as antimicrobial, anti-inflammatory, antioxidant, and anti-carcinogenic. Objective: The aim is to determine the protective effects of DMF against amyloid beta (Aβ)-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans model of AD. Materials and Methods: The therapeutic potential of DMF treatments (5, 25, and 50 μM) was investigated to counteract Aβ paralysis and oxidative stress through paralysis assay, reactive oxygen species (ROS) detection, protein carbonylation, aldicarb assay, and mRNA quantification using transgenic C. elegans model of AD. Results: The present study reports that DMF effectively delayed Aβ-induced paralysis, attenuated ROS level reduced protein carbonylation and conferred aldicarb resistance. In addition, DMF was also found to up-regulate the expression of stress modulating (sod-1, sod-2, sod-3, ctl-1, hsp-16.2, and gst-4), acetylcholine transporter(unc-17), regulator of nicotinic acetylcholine receptor (unc-50), and choline acetyltransferase (cha-1) related genes. Conclusion: These findings suggest DMF may provide protection against Aβ toxicity and oxidative stress due to its antioxidant activity. Therefore, the bioactive flavonoid DMF may provide invaluable medicinal and health benefits which can delay the onset of age-related diseases. Abbreviations used: DMF: 5, 7-dihydroxy-4-methoxyflavone; ROS: Reactive oxygen species; C. elegans: Caenorhabditis elegans; AD: Alzheimer's disease; Aβ: Amyloid beta; DMSO: Dimethyl sulphoxide; NGM: Nematode growth media; ACh: Acetylcholine; Ald: Aldicarb; APP: Amyloid precursor protein.
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