Polyphenols from <em>Sorghum bicolor</em> Suppress Tauopathies: Evidence from <em>In Silico</em> and In <em>Vivo</em> Studies — The Association Specialists

Polyphenols from Sorghum bicolor Suppress Tauopathies: Evidence from In Silico and In Vivo Studies (21160)

Rasheed A Abdulraheem 1 2 , Prashant Bharadwaj 1 2 , Ralph N Martins 1 2 3 , Zhaoyu Li 4 , Ranil Coorey 5 , Stuart Johnson 6 , Binosha fernando 1 2
  1. Edith Cowan University, Perth, WA, Australia
  2. Alzheimer’s Research Australia, Perth, WA, Australia
  3. Faculty of Medicine, Human and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
  4. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia
  5. School of Molecular and Life Sciences, Curtin University, Perth, WA, Australia
  6. Ingredients by Design Pty Ltd, Perth, WA, Australia

Polyphenols, abundant in plant sources, have antioxidant and anti-inflammatory properties, which may benefit neurological health. Sorghum bicolor, a cereal grain rich in polyphenols, presents promising therapeutic candidate for tauopathies. Studies have suggested that polyphenols inhibit tau protein aggregation, potentially mitigating the progression of neurodegeneration.

Objective: In this context, our study investigates the inhibitory effects of polyphenol extracts from Sorghum bicolor on tauopathies using computational molecular docking simulations and a validated Caenorhabditis elegans model of tau aggregation. By integrating in silico predictions with in vivo validation, we elucidate the therapeutic potential of Sorghum bicolor polyphenols in combating tau-related neurodegenerative diseases.

Method: Polyphenols identified from Sorghum bicolor were docked against tau protein (503L PHF in Alzheimer's brain) using MCULE, RCSB Protein Data Bank and Discovery Studio Analyser. We evaluated the effects of these polyphenol extracts on tau-induced toxicity in Caenorhabditis elegans through body movements, chemosensory, and lifespan assays.

Results: The polyphenols exhibited strong binding affinities with specific amino acid residues (Valine, Glutamic Acid, and Isoleucine) of the tau protein, as identified by consensus scoring methods and binding pockets from docking poses. These interactions involved hydrogen bonds that potentially inhibit the formation of PHF. At a concentration of 500 µg/mL, the polyphenol extracts improved the healthspan and extended lifespan of the tau model of Caenorhabditis elegans by two days compared to controls.

Conclusions: Our findings suggest that Sorghum bicolor polyphenols hold promise as a complementary therapy for tau-associated neurodegenerative diseases, particularly Alzheimer's disease. However, further investigation is warranted to elucidate the underlying mechanisms.