Therapeutic Potential of Phytoconstituents in Management of Alzheimer’s Disease

Table 1

Neurological hypothesis and effect of phytoconstituents in AD.

Types of hypothesis	Class	Natural compounds	Pharmacological/mechanism of action	References
Secretase hypothesis	Neuronal cells and cell-free system	Myricetin	Reduced the generation of Aβ	[11]
			It also decreased the production of Aβ via upregulation of the α-secretase actions and/or downregulation of β-secretase actions	[12]
		Tannic acid	Prevention of cognitive decline, inhibition of the activity of β-secretase, and reduction of the AD-like pathology in transgenic mice	[13]
Aβ aggregation	Biflavonoids	Taiwaniaflavone and monoflavonoid apigenin	Observed that the biflavonoid was more effective at decreasing the extension of Aβ fibril	[14]
Nontoxic Aβ oligomers	Oligomers	Small molecules of flavonoids	Soluble Aβ oligomers are the main toxic species of Aβ triggering neurodegeneration; Aβ oligomers over monomeric fibrillary Aβ are started as active therapeutics for nullifying and pointing Aβ toxicity in case of AD	[15–17]
Aβ-induced neurotoxicity	Polyphenols and flavonoids	Quercetin	Inhibiting the formation of Aβ fibril, quercetin was less effective in terms of improving the toxicity of Aβ as compared to myricetin	[18]
Tau hyperphosphorylation	Glycogen synthase kinase 3 beta (GSK-3β)	Linarin	Prevents the neurotoxicity induced by Aβ (25–35) via PI3K/Akt activation, which can subsequently lead to promotion of Bcl-2 regulation and inhibition of GSK-3β. It plays a key role in neuroprotection and AChE inhibition	[19]
Oxidative stress	Biflavonoid	Morelloflavone	Potential to act as a potent inhibitor of lipid peroxidation	[20]
	Natural flavonoid	Silybum marianum	Promotes the viability of neuron upon hydrogen peroxide insult	[21, 22]
RAGE	Polyphenols	Camellia sinensis	RAGE plays a role as inducer of oxidative stress (OS) and AD pathophysiology	[23, 24]