Table 3.
Studies of polarized microglia-based therapy in ischemic stroke.
| Drug/agent | Model | Mechanism | Effect | Reference |
|---|---|---|---|---|
| TWS119 | MCAO mice | Wnt/β-catenin pathway activator | Modulate microglia to anti-inflammatory phenotype | [115] |
| Melatonin | MCAO mice BV2 microglia |
STAT3 pathway activator |
Decrease expression of pro-inflammatory markers and increased expression of anti-inflammatory markers | [116] |
| HAMI3379 | Rat | CysLTR antagonist NF-κB pathway |
Inhibit microglia M1 polarization and promote microglia polarization toward M2 phenotype | [117] |
| β-caryophyllene (BCP) | MCAO Mice |
TLR4 pathway antagonist |
Decrease the secretion of pro-inflammatory cytokines (IL-1β, TNF-α) and polarize microglia towards the M2 phenotype | [118] |
| Suberoylanilide hydroxamic acid | MCAO mouse | Histone deacetylase inhibitors | Suppresse M1 cytokine expression (IL-6, TNF-α, and iNOS) while promoted the transcription of M2 cytokines (Arg-1 and IL-10) | [119] |
| Isosteviol Sodium (STV-Na) | MCAO mouse BV2 microglia |
miR-146a-5p | Promote M2 polarization and inhibit M1 response | [120] |
| Baicalein | MCAO rat | NF-κB antagonist | Reduced expression of the M1 marker (CD 16 and CD86), and increase expression of the M2 marker, (CD 163 and CD206) | [121] |
| Berberine | MCAO mice | AMPK activator |
Inhibit M1 polarization and promote M2 polarization | [122] |
| CKLF1 | MCAO mice | NF-κB activator | Modulated primary microglia skew toward M1 phenotype | [123] |
| Exosomes from LPS-stimulated macrophages | Rat | Skew the microglial functional polarity from M1 toward an anti-inflammatory M2 phenotype. | [124] | |
| Nicotinamide phosphoribosyltransferase (NAMPT) | MCAO mice | Inhibite pro-inflammatory microglia, promoted microglia polarization toward the anti-inflammatory phenotype, | [125] | |
| Propagermanium | MCAO mice | CCR2 inhibitor | Inhibite inflammatory cytokines releasing, such as TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-17, and IL-23, inhibite CD16 expressed in microglia. | [126] |
| Glycine | SpragueDawley rats BV-2 cells | NF-κB p65 inhibitor |
Inhibite M1 microglial polarization | [127] |
| Xuesaitong | MCAO mice | STAT3 inhibitor |
Promote the polarization of microglia to an M2 phenotype | [128] |
| Sphingosine 1-phosphate receptor subtype 3 (S1P) |
MCAO mice | MAPK and Akt activator |
Involve its modulation of microglial activation and M1 polarization | [129] |
| L-3-n-Butylphthalide | MCAO mice | Skewing M1 microglia polarization towards M2 | [130] | |
| α-Lipoic acid | MCAO rat | NF-κB inhibitor |
Induced the polarization of microglia to the M2 phenotype, modulated the expression of IL-1β, IL-6, TNF-α and IL-10, | [131] |
| Hypothermia | MCAO mice | Reduce the number of CD16-positive M1 microglia and increase the numbers of CD206-positive M2 microglia | [132] | |
| Ischemic postconditioning | Rat | Polarize to a ramified morphology with higher expression of M2-like markers | [133] | |
| XQ-1H | MCAO mice BV2 microglia |
PPARγ pathway activator |
Regulate microglia polarized from pro-inflammatory into anti-inflammatory phenotype | [134] |
| Salidroside | MCAO mice | Reduce the expression of M1 microglia markers and increased the expression of M2 microglia | [135] | |
| Anisalcohol | BV2 microglia |
NF-κB inhibitor MAPK activation |
Down-regulated the expression of the M1 marker CD16/32 and up-regulated that of the M2 marker CD206. | [136] |
| Fas ligand incapacitation | Mouse | NF-κB pathway |
Alleviate CD4 T cells-induced inflammation induce M1 microglia polarization | [137] |
| CD8 receptor | MCAO rat | CD8 signaling | Repolarize IL4-treated M2 cells to an M1 phenotype | [138] |
| Hyperforin | Mice | Shift from M1 to M2 phenotypes | [139] | |
| Apoptosis signal-regulating kinase 1 | BV2 microglia | Control the polarization of M1/M2 | [140] | |
| Erythropoietin | MCAO mice | Reduce M1 microglia and increase M2 microglia | [141] | |
| Curcumin | MCAO mice | Promot M2 microglial polarization and inhibite microglia-mediated pro-inflammatory responses | [142] | |
| Hydrogen sulfide | MCAO mice | AMPK Pathway activation |
Promoted a shift from pro-inflammatory phenotypes toward anti-inflammatory phenotypes in microglial polarization. | [143] |
| HP-1c | Mice | AMPK-Nrf2 pathway activation | Shift the M1/M2 polarization | [144] |
| Progesterone | Rat | Modulate polarized microglia | [145] | |
| Long noncoding RNA H19 | MCAO mice BV2 microglia | HDAC -dependent M1 microglial polarization | [110] | |
| Lipoxin A | MCAO rat | Increase anti-inflammatory M2 microglia | [146] | |
| Thiamet G | MCAO mice BV2 microglia |
NF-κB inhibitor |
Decrease expression of the M1 markers, and increase expression of the M2 markers | [147] |