TABLE 1.
Summary of in vitro studies on the neuroprotective effects of lipoxins.
| Cell type | Model | Agent | Effects | References |
|---|---|---|---|---|
| Neural stem cells | ||||
| Murine neural stem cells | — | ATL, LXA4 | Attenuated growth of NSCs by inducing the expression of epidermal growth factor receptor, cyclin E, p27, and caspase 8 | Wada et al. (2006) |
| Neurons | ||||
| SH-SY5Y cells | STS-induced neurotoxicity | LXA4 | Anti-apoptosis by targeting GPR32 | Zhu et al. (2016) |
| HT-22 cells | Glutamate-induced neurotoxicity | LXA4, LXB4 | LXA4: cell death reduced by targeting FPR2/ALX; LXB4: cell death reduced by influencing mitochondrial activity | Livne-Bar et al. (2017) |
| Rat primary cortical neurons | OGD | LXA4 | Anti-apoptosis, anti-inflammation and anti-oxidation by inhibiting IκB/NF-κB pathway | Zhu et al. (2020) |
| Mouse primary cortical neurons | Serum deprivation | LXA4, LXB4 | Cell death reduced only by LXB4 | Livne-Bar et al. (2017) |
| RGCs | PQ-induced oxidative stress | LXA4, LXB4 | LXA4: RGC survival rescued; LXB4: both RGC survival and neurite degeneration rescued | Livne-Bar et al. (2017) |
| Microglia | ||||
| BV2 cells | Stimulated by LPS | ATL | NO, iNOS, IL-1β and TNF-α reduced by inhibiting NF-κB, ERK, p38 MAPK and AP-1 signaling pathways; ROS reduced by inhibiting the function of NADPH oxidase; regulated the activation and polarization of microglia via the Notch Signaling Pathway | Wang et al. (2011), Wu et al. (2012c), Wu et al. (2019b) |
| BV2 cells | OGDR | LXA4 | Regulated the polarization of microglia through the Notch signaling pathway | Li et al. (2021) |
| BV2 cells | Stimulated by Aβ1-42 | LXA4 | IL-1β and TNF-α reduced by inhibiting NF-κB signal pathway | Wu et al. (2011) |
| Human CHME3 cells | Stimulated by Aβ42 | LXA4 | No significant effect on microglial activation and phagocytosis | Zhu et al. (2016) |
| Astrocytes | ||||
| Rat primary astrocytes | OGDR | LXA4 | LTB4, LTC4 and 5-LOX nuclear translocation reduced involving ALXR/ERK pathway; anti-oxidation by activating Nrf2 pathway and increasing the level of HO-1, GSH, and p62 | Wu et al. (2012a), Wu et al. (2015) |
| Rat primary astrocytes | Stimulated by LPS | ATL, LXA4 | NO, PGE2, iNOS and COX-2 reduced by inhibiting NF-κB signal pathway; down-regulate the expression of AQP4 | Yao et al. (2014), Wu et al. (2019a) |
| 1321N1 human astrocytoma cells | IL-1β-induced stimulation | LXA4 | IL-8 and ICAM-1 reduced by inhibiting NF-κB signal pathway | Decker et al. (2009) |
AP-1, activating protein-1; ATL, aspirin-triggered lipoxin A₄; Aβ, β-amyloid; COX-2, cyclooxygenase 2; ERK, extracellular signal-regulated kinase; FPR2/ALX, formyl peptide receptor 2/LXA4 receptor; GPR, G protein-coupled receptor; GSH, glutathione; HO-1, heme oxygenase; IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; IκB, inhibitor κB; LOX, lipoxygenase; LPS, lipopolysaccharide; LT, leukotriene; LX, lipoxin; MAPK, mitogen-activated protein kinase; NADPH, nicotinamide adenine dinucleotide phosphate; NF-κB, nuclear factor kappa B; NO, nitric oxide; Nrf2, nuclear factor erythroid 2-related factor 2; OGD/R, oxygen-glucose deprivation/recovery; PQ, paraquat; RGCs, retinal ganglion cells; ROS, reactive oxygen species; STS, staurosporine; TNF, tumor necrosis factor.