Nutrients, Vol. 17, Pages 516: Investigating the Impact of Sorghum on Tau Protein Phosphorylation and Mitochondrial Dysfunction Modulation in Alzheimer’s Disease: An In Vitro Study

Nutrients, Vol. 17, Pages 516: Investigating the Impact of Sorghum on Tau Protein Phosphorylation and Mitochondrial Dysfunction Modulation in Alzheimer’s Disease: An In Vitro Study

Nutrients doi: 10.3390/nu17030516

Authors:
Nasim Rezaee
Eugene Hone
Hamid Sohrabi
Rasheed Abdulraheem
Stuart K. Johnson
Stuart Gunzburg
Ralph N. Martins
W. M. A. D. Binosha Fernando

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with poorly understood pathology. Elevated tau, phospho-tau and mitochondrial dysfunction are significantly correlated with an increased risk of AD and are therefore targets for disease-modifying therapy. In this study, we examined the effects of polyphenolic extracts from six different varieties of sorghum: Shawaya short black-1 (Black), IS1311C (Brown), QL33/QL36 (Red), B923296 (Red), QL12 (White), and QL33 (Red) on the attenuation of beta amyloid-induced phospho-tau levels, total tau levels, and mitochondrial dysfunction in neuronal cells. Method: Tau proteins (231 (pT231), Serine- 199 (pS199), and total tau proteins (T-tau)) were detected and quantified using sandwich ELISA kits, while mitochondrial dysfunction was measured in terms of mitochondrial membrane potential (Δψm) and adenosine triphosphate (ATP) levels. Results: Almost all varieties of the sorghum extracts reduced the beta amyloid-induced pS199 and pT231 levels (p ≤ 0.05). The optimum concentration of QL33/QL36 (1000 µg/mL), QL12 (2000 µg/mL), and QL33 (2000 µg/mL) strongly attenuated the phospho-tau level. Sorghum IS1311C (750 µg/mL) showed the highest Δψm reduction (39.8%), whereas QL33 (2000 µg/mL) most strongly improved the ATP level (37.7%) (p ≤ 0.01). For both Δψm and ATP assays, the least activity was observed in sorghum B923296 at 21% and 25.5%, respectively (p ≤ 0.01). Conclusions: The polyphenol extracts from sorghum attenuated the tau toxicity and Aβ-induced mitochondrial dysfunction in a variety- and dose-dependent manner and made a promising disease-modifying agent against AD. However, extensive research is needed to validate the efficacy of the sorghum extracts prior to animal and clinical studies.

​Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with poorly understood pathology. Elevated tau, phospho-tau and mitochondrial dysfunction are significantly correlated with an increased risk of AD and are therefore targets for disease-modifying therapy. In this study, we examined the effects of polyphenolic extracts from six different varieties of sorghum: Shawaya short black-1 (Black), IS1311C (Brown), QL33/QL36 (Red), B923296 (Red), QL12 (White), and QL33 (Red) on the attenuation of beta amyloid-induced phospho-tau levels, total tau levels, and mitochondrial dysfunction in neuronal cells. Method: Tau proteins (231 (pT231), Serine- 199 (pS199), and total tau proteins (T-tau)) were detected and quantified using sandwich ELISA kits, while mitochondrial dysfunction was measured in terms of mitochondrial membrane potential (Δψm) and adenosine triphosphate (ATP) levels. Results: Almost all varieties of the sorghum extracts reduced the beta amyloid-induced pS199 and pT231 levels (p ≤ 0.05). The optimum concentration of QL33/QL36 (1000 µg/mL), QL12 (2000 µg/mL), and QL33 (2000 µg/mL) strongly attenuated the phospho-tau level. Sorghum IS1311C (750 µg/mL) showed the highest Δψm reduction (39.8%), whereas QL33 (2000 µg/mL) most strongly improved the ATP level (37.7%) (p ≤ 0.01). For both Δψm and ATP assays, the least activity was observed in sorghum B923296 at 21% and 25.5%, respectively (p ≤ 0.01). Conclusions: The polyphenol extracts from sorghum attenuated the tau toxicity and Aβ-induced mitochondrial dysfunction in a variety- and dose-dependent manner and made a promising disease-modifying agent against AD. However, extensive research is needed to validate the efficacy of the sorghum extracts prior to animal and clinical studies. Read More

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