Table 2.

Therapeutic approach to combat neuroinflammation in AD

Phytochemical origin	Essential components			Effects	Significance in AD		References
Natural products
Turmeric	Curcumin Tetrahydrocurcumin			Inhibits gliosis Reduces oxidized protein Disaggregates Aβ Prevent synaptic toxicity	Modulates inflammation Reduces Aβ aggregates Protects synapses Improves cognition		[137,138,139,140,141]
Morus alba	Quercetin			Inhibits the NF-kB pathway Upregulates the anti-oxidant defense system NRf2/HO-1 axis Regulates apoptosis	Reduces neuroinflammation Reduces oxidative stress		[142, 143]
Grapevine and other fruits	Resveratrol			Inhibits gliosis Upregulates SIRT-1 expression Reduces oxidative stress	Reduces neuroinflammation Decreases Aβ aggregates Improves cognition		[144, 145]
Ginkgo biloba	Ginkgolides			Increases SIRT-1 expression Inhibits NF-kB pathway Upregulated HO-1 expression Upregulates anti-apoptotic protein expression	Reduces neuroinflammation Anti-apoptotic Protects neurons		[146–149]
Sinomenine acutum	Sinomenine			Inhibits gliosis Inhibit NADPH oxidase Prevent DNA damage	Reduces neuroinflammation Reduces ROS production Protects neuron		[150–152]
Name		Target	Effects			Significance in AD		References
Synthetic drugs:
GC021109		P2XY	Enhances phagocytosis by microglia			Inhibits neuroinflammation		[153]
Azeliragon		Antagonist of RAGE	Prevent Aβ-induced neurotoxicity			Neuroprotection		[154]
Pioglitazone		Agonist of PPARγ	Ameliorates metabolism of neuron Reduces neuroinflammation Reduces oxidative stress			Improves learning and memory Improves synaptic activity Reduces Aβ and tau pathology		[155]
Ibuprofen		COX	Inhibits cytokine production			Reduces neuroinflammation		[159]
Cromolyn		Microglia	Inhibits release of inflammatory cytokines			Reduces neuroinflammation		[160]
Neflamapimod		Intracellular enzyme p38MAPKα	Inhibits inflammatory pathway			Improves cognition Ameliorates synaptic dysfunction		[161,162,163]