Inflammation and Alzheimer’s Disease: Mechanisms and Therapeutic Implications by Natural Products

Table 1

Phytochemicals that affect neuroinflammation in animal and cellular AD models.

Name of the plant	Phytochemicals	Experimental model used	Mechanism of action	References
Turmeric, Curcuma longa	Curcumin	SQ-injected D-galactose-induced mouse model	It activates ERK/PKC-arbitrated CREB regulation and Akt/GSk3β-arbitrated regulation. Stimulates BDNF and regulates the levels of caspase-3, TNF-α, and NFкB	[206]
Tea plant, Camelia sinensis	Epigallocatechin-3-galate	Human astrocytoma U373MG cells	It regulates the activation of NFкB and MAPK; reduces the levels of IL-1, IL-6, IL-8, and Cox-2; promotes the secretion of BDNF and NGF; attenuates caspase-3 and ROS levels	[207]
Sweet orange, Citrus sinensis	Naringenin	Hypoxia rat model	It initiates the activation of Nrf2/ARE signaling; enhances the levels of antioxidants; attenuates the levels of NO, cytokines, and NFкB signaling	[208]
Mangosteen, Garcinia mangostana	α-Mangostin	C57BL/6J triple transgenic mouse model	Plays an essential role in the regulation of inflammatory process; enhances BDNF expression and attenuates the phosphorylation of tau; regulates the levels of IL-1β, TNF-α, and caspase-3	[209]
Indian pennywort, Centella asiatica	Asiatic acid	Aluminium-induced rat model	Asiatic acid attenuates the Aβ toxicity by reducing the levels of APP, Aβ1-42, and β- and γ-secretases. It also reduces the expression of inflammatory mediators in the hippocampus and cortex and enhances the expression of GFAP and Iba-1	[99]
Black seed, Nigella sativa	Thymoquinone	LPS/IFN-γ-activated BV-2 microglia	Inhibition of NFкB initiated neuroinflammation, suppression of inflammatory markers (NO, IL-1β, and TNF-α), and production by regulating PI3K/Akt/NF-кB signaling	[210]
Ginger, Zingiber officinale	Gingerol	ICV-STZ-induced mouse model	It ameliorates the cognitive and behavioral dysfunction and AD-like pathology. It enhances the α-secretase activity and attenuates cerebral Aβ-42, β-secretase, APH1a activity, and COX-2-associated neuroinflammation	[211]
Citrus, Citrus × sinensis	Hesperidin	Aβ-induced APPswe/PS1dE9 transgenic mouse model	It exhibits the inhibitory effect on inflammatory mediators (TNF-α, IL-1β, COX-2, and iNOS). It enhances antioxidant defense and improves cognitive function. It attenuates the Aβ pathology by reducing H2O2 levels and restoring depleting GSH levels and total antioxidant capacity	[212]
Grape vine, Vitis vinifera	Quercetin	SAMP8 (senescence model)	It protects neuronal cells by reducing oxidative stress and neuroinflammation. It inhibits Aβ aggregation and tau phosphorylation. It suppresses neuroinflammatory processes by decreasing proinflammatory cytokines (iNOS, COX-2, and IL-1β) and reduces the levels of GFAP in the hippocampus	[213]