Potential of Sorghum Polyphenols to Prevent and Treat Alzheimer's Disease: A Review Article

Abstract

Alzheimer's disease (AD) is characterized by the excessive deposition of extracellular amyloid-beta peptide (Aβ) and the build-up of intracellular neurofibrillary tangles containing hyperphosphorylated tau proteins. This leads to neuronal damage, cell death and consequently results in memory and learning impairments leading to dementia. Although the exact cause of AD is not yet clear, numerous studies indicate that oxidative stress, inflammation, and mitochondrial dysfunction significantly contribute to its onset and progression. There is no effective therapeutic approach to stop the progression of AD and its associated symptoms. Thus, early intervention, preferably, pre-clinically when the brain is not significantly affected, is a better option for effective treatment. Natural polyphenols (PP) target multiple AD-related pathways such as protecting the brain from Aβ and tau neurotoxicity, ameliorating oxidative damage and mitochondrial dysfunction. Among natural products, the cereal crop sorghum has some unique features. It is one of the major global grain crops but in the developed world, it is primarily used as feed for farm animals. A broad range of PP, including phenolic acids, flavonoids, and condensed tannins are present in sorghum grain including some classes such as proanthocyanidins that are rarely found in others plants. Pigmented varieties of sorghum have the highest polyphenolic content and antioxidant activity which potentially makes their consumption beneficial for human health through different pathways such as oxidative stress reduction and thus the prevention and treatment of neurodegenerative diseases. This review summarizes the potential of sorghum PP to beneficially affect the neuropathology of AD.

Keywords: Alzheimer’s disease; amyloid-beta; antioxidant; flavonoids; mitochondrial dysfunction; polyphenols; sorghum; tau.

Figure 1

Alzheimer’s disease (AD) hypotheses (Swerdlow, ; Altinoglu and Adali, 2020). The six most common AD hypotheses include the amyloid cascade hypothesis, tau hypothesis, neuroinflammation, cholinergic hypothesis, mitochondrial dysfunction hypothesis, and oxidative stress hypothesis which are explained separately through the article. All the these mechanisms can interact with each other.

Figure 2

Schematic of Aβ hypothesis. APP is sequentially cleaved via amyloidogenic or non-amyloidogenic pathways. In the non-amyloidogenic pathway, it is cleaved by α-secretase, resulting in the production of the sAPPα. In the amyloidogenic pathway, APP is initially cleaved by β-secretase, then γ-secretase, resulting in the production of Aβ peptides. Abbreviations: APP, amyloid precursor protein; PSEN1, presenilin 1; PSEN2, presenilin 2; Aβ, amyloid beta.

Figure 3

Schematic of tau hypothesis. Aggregate stress condition is a condition in which Aβ aggregation alters the kinase/phosphatase activity that can lead to hyperphosphorylation of tau resulting in PHF formation which consequently leads to neuronal dysfunction and dementia (Verwilst et al., 2018). Abbreviations: PHF, paired helical filament; NFT, neurofibrillary tangles.

Figure 4

Polyphenols classifications. PP are divided into two main groups of flavonoids and non-flavonoids (El Gharras, ; Lakey-Beitia et al., 2015).

Figure 5

Different genotypes of sorghum grain: black pericarp, red pericarp, white pericarp, brown pericarp, and orange pericarp varieties. Selection of the most potent varieties of sorghum is crucial for health and medical-related purposes. Picture adopted from Barmac (2021).

Figure 6

Chemical structure of important flavonoids of sorghum with anti-AD activities. (A) Anthocyanidins (a: R₁= R₂ = OCH₃: malvidin, R1 = OH, R2 = H: cyanidin, R1=OCH₃, R₂ = H: peonidin, b: R₁ = H, R₂ = H, R₃= H: apigeninidin, R₁ = H, R₂ = Glc, R₃= H: apigeninidin-5-glucoside, R₁ = H, R₂ = H, R₃=CH₃: 7- methoxyapigenindin, R₁ = OH, R₂ = H, R₃= H: luteolinidin, R₁ = OH, R₂ = Glc, R₃= H: luteolinidin-5-glucoside, R₁ = OH, R₂=CH₃, R₃= H: 5-methoxyluteolinidin), (B) others (a: apigenin b: luteolin c: naringenin d: kaempferol e: quercetin f: taxifolin g: catechin; Awika et al., ; Lakey-Beitia et al., ; Vanamala et al., ; Jabir et al., 2018).

Figure 7

Chemical structure of important non-flavonoids of sorghum with anti-AD activities (Lakey-Beitia et al., ; Girard and Awika, ; Jabir et al., ; A: ferulic acid, B: caffeic acid, C: cinnamic acid, D: sinapic acid, E: resveratrol, and F: tannins).