Table 2.

Natural products and their bioactive compounds with neuroprotective activities in treating Alzheimer's disease.

Plant extracts/phytochemicals (plant source)/natural products/substances	Study model	Neuroprotective activities	References
Turmeric (powdered rhizome of Curcuma longa Linn (5% curcumin)	Case studies of 3 patients with progressive dementia	(i) Improvement in the behavioral symptoms and quality of life	[256]
Coconut oil enriched Mediterranean diet	44 patients with Alzheimer's disease	(i) improved the cognitive functions	[257]
Germinated brown rice (Malaysian mixed varieties; MR219 and MR220)	Aβ (1–42)-induced toxicity in SH-SY5Y cells	(i) Reduced intracellular ROS generation	[258]
		(ii) Attenuated Aβ (1–42)-induced cell death
Huperzine A isolated from Huperzia serrata	Hypoxic-ischemic and glutamate-induced brain injury and cytotoxicity	(i) Reduce Aβ (1–42)-induced neuronal cell death	[259]
		(ii) Decrease oxidative damage
		(iii) Protects neurons from cytotoxic and apoptosis
		(iv) Inhibited the glutamate toxicity
Huperzine A isolated from Huperzia serrata	50 patients with Alzheimer's disease	(i) Improvement in memory, cognitive, and behavior functions	[260]
Methanolic extract of Lactuca capensis thunb. leaves	Aβ (1–42)-induced neurotoxicity in rats	(i) Ameliorated cognitive impairment and memory deficits	[261]
		(ii) Decreased acetylcholinesterase activity
		(iii) Restored the level of GSH and the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase)
		(iv) Decreased the lipid peroxidation and protein oxidation level
		(v) Attenuated hippocampal apoptosis by lowering the enrichment factor of apoptosis level
		(v) Increased BDNF mRNA copy number
		(vi) Decreased IL-1β mRNA copy number
Osmotin, a plant protein extracted from Nicotiana tabacum	Aβ (1–42)-treated mouse and Aβ (1–42)-induced neurotoxicity in HT22 cells	(i) Reversed synaptic deficits	[262]
		(ii) Attenuated Aβ accumulation and BACE-1 expression
		(iii) Increased spontaneous alternation behavior
		(iv) Ameliorated memory impairment in a Y-maze test
		(v) Alleviated the hyperphosphorylation of the tau protein at serine 413 through the regulation of the aberrant phosphorylation of p-PI3K, p-Akt (serine 473), and p-GSK3β (serine 9)
		(vi) Prevented Aβ (1–42)-induced apoptosis and neurodegeneration in the Aβ (1–42)-treated mouse
		(vii) Attenuated Aβ (1–42)-induced neurotoxicity in vitro of neuronal HT22 cells and primary cultures of hippocampal neurons
Safflower yellow (natural safflower aqueous extract)	Aβ (1–42)-induced rats	(i) Improved short- and long-term memory of rats	[263]
		(ii) Decreased inflammatory markers (iNOS, IL-1β, IL-6, and TNF-α levels)
		(iii) Reduced neuronal cell loss in the hippocampus and cortex
		(iv) Inhibited the activation of glial cells
		(v) Downregulated M1 microglial markers (iNOS and CD86)
		(vi) Upregulated M2 microglial markers (arginase-1, CD2066, and YM-1)
Tabernaemontana divaricata root extract	Aβ (25–35)-induced mouse	(i) Prevented memory loss	[264]
		(ii) Decreased lipid peroxidation
		(iii) Increased neuronal density in the hippocampus
Yacon (Smallanthus sonchifolius (poepp. and endl.) H. Robinson) leaf extract	Aβ (25–35)-induced rats	(i) Decreased oxidative stress in the hippocampus	[265]
		(ii) Prevented memory deficits
		(iii) Attenuated the hippocampal damage