Phytochemicals as regulators of microglia/macrophages activation in cerebral ischemia

• Published in: Pharmacological research Vol. 165; p. 105419
• Main Authors: Subedi, Lalita, Gaire, Bhakta Prasad
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.03.2021
• Subjects: Animals; Bioactive phytochemicals; Brain Ischemia - drug therapy; Cerebral ischemia/Stroke; Humans; Macrophage Activation - drug effects; Macrophages - drug effects; Microglia - drug effects; Microglia/Macrophages; Neuroinflammation; Neuroinflammatory Diseases - drug therapy; Neuroprotection; Neuroprotective Agents - therapeutic use; Phytochemicals - therapeutic use; BBB; JNK; rtPA; Quercetin (CID: 5280343); Scutellarin (CID: 185617); ICAM-1; AP-1; I/R; MPO; MyD88; Cerebral ischemia/Stroke; BCCAO; NF-κB; IFN-γ; 6-shogaol (CID: 5281794); Arg-1; PI3K; Edaravone (CID: 4021); iNOS; WHO; 2-VO; IL; Baicalin (CID: 64982); Nurr1; MAPK; PPARγ; ROS; AMPK; 6-paradol (CID: 94378); TRIF; TLR4; tMCAO; ERK; NO; Neuroprotection; CamKII; MCP-1; COX-2; Prx6; CNS; HO-1; Iba1; LPS; DAMPs; ASC; Bioactive phytochemicals; Nrf2; Eupatilin (CID: 5273755); Resveratrol (CID: 445154); NLRP3; TGF-β; Epigallocatechin gallate (CID: 65064); Microglia/Macrophages; MCAO; CD; PGE2; Curcumin (CID: 969516); IKKαβ; BDNF; MMPs; STAT3; Neuroinflammation; 4-VO; OGD; GFAP; ICH; TNF-α; DNA; pMCAO; BrdU
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2021.105419

[Display omitted] The search for novel therapeutic agents for the management of cerebral ischemia/stroke has become an appealing research interest in the recent past. Neuroprotective phytochemicals as novel stroke drug candidates have recently drawn significant interests from stroke scientists due to their strong brain protective effects in animal stroke models. The underlying mechanism of action is likely owing to their anti-inflammatory properties, even though other mechanisms such as anti-oxidation and vasculoprotection have also been proposed. It is generally held that the early proinflammatory responses after stroke can lead to a secondary brain injury, mainly due to the damaging effect exerted by over-activation of brain resident microglial cells and infiltration of circulating monocytes and macrophages. This review focuses on the anti-inflammatory properties of bioactive phytochemicals, including activation and polarization of microglia/macrophages in the post-ischemic brain. The latest studies in animal stroke models demonstrate that this group of bioactive phytochemicals exerts their anti-inflammatory effects via attenuation of brain proinflammatory microglia and macrophages M1 polarization while promoting anti-inflammatory microglial and macrophages M2 polarization. As a result, stroked animals treated with brain protective phytochemicals have significantly fewer brain active M1 microglia and macrophages, smaller brain infarct volume, better functional recovery, and better survival rate. Therefore, this review provides insights into a new category of drug candidates for stroke drug development by employing neuroprotective phytochemicals.