TABLE 1.

Effects and potential mechanisms of astaxanthin in modulating neuroinflammation.

Disease Model	Animal or Cell Line	Formulation, Dosage, and Treatment Time	Effects	Potential Target	References
Alzheimer’s disease	APP/PS1 double-transgenic mouse model	0.2% docosahexaenoic-acid-acylated astaxanthin diesters (DHA-AST) administered (p.o.) in AIN-93G diet for 60 days	Suppressed activation of microglia and astrocytes, inhibited inflammasome activation and attenuated proinflammation cytokine production	Unclear	Che et al. (2018)
	AD rat model induced by cerebral ventricle injection of Aβ (1–42)	0.5 mg/kg/day or 1 mg/kg/day astaxanthin was administered (p.o.) for 28 days beginning from the 8th day of cerebral ventricle Aβ(1–42) injection	Attenuated proinflammation cytokine production and oxidative stress in the hippocampus	Unclear	Rahman et al. (2019)
	AppNL-G-F transgenic mouse model	0.02% astaxanthin as free form (w/w) was administered in the diet for about 5 months	Attenuated oxidative stress and microglia accumulation in the hippocampus	Unclear	Hongo et al. (2020)
	Rat model induced by intraventricular infusion of ferrous amyloid buthionine (FAB)	1 ml/kg (body weight)/day astaxanthin administered in 0.5% DMSO in saline (i.p.) for 7 days	Suppressed activation of microglia and astrocytes	Nrf2	Chen et al. (2021a)
Depression	LPS-induced depressive-like mouse model	Pretreatment with 20,40, or 80 mg/kg trans-astaxanthin (p.o.) for 7 days	Attenuated proinflammation cytokine production in the hippocampus and prefrontal cortex	NF-κB	Jiang et al. (2016)
	Diabetes-related depressive-like mouse model	25 mg/kg/day astaxanthin in olive oil (p.o.) administered for 10 weeks	Suppressed astrocytes activation and attenuated proinflammation cytokine production	Unclear	Zhou et al. (2017)
Epilepsy	Status epilepticus rat mode	30 mg/kg/day astaxanthin in DMSO administered for 2 weeks	Suppressed microglia activation and attenuated proinflammation cytokine production	Unclear	Wang et al. (2020b)
	Status epilepticus rat mode	30 mg/kg astaxanthin in polyethylene glycol and tri-distilled water (1:1) was administered seven times (i.p.) in 14 days after establishing the model	Attenuated proinflammation cytokine production	Nrf2 and NF-κB	Deng et al. (2019)
Subarachnoid hemorrhage	Rat	25 or 75 mg/kg astaxanthin in olive oil (p.o.) administered 30 min after subarachnoid hemorrhage	Attenuated BBB disruption and proinflammation cytokine production	NF-κB	Zhang et al. (2014a)
Spinal cord injury	Rat	10 μl astaxanthin in 5% DMSO at a concentration of 0.2 mM injected (i.t.) 30 min after injury	Attenuated proinflammation cytokine production	MAPK	Fakhri et al. (2018)
Diabetes-induced neuropathy	Diabetic mouse model	25 mg/kg/day astaxanthin (p.o.) in olive oil for 7 days	Suppressed microglia activation and attenuated proinflammation cytokine production	NF-κB	Zhou et al. (2015)
General neuroinflammation	LPS-induced mouse model	20, 40, or 80 mg/kg astaxanthin in 0.5% sodium carboxy methyl cellulose administered (p.o.) for seven consecutive days before LPS injection	Attenuated proinflammation cytokine production	NF-κB	Jiang et al. (2016)
	LPS-induced mouse model	30 or 50 mg/kg/day astaxanthin in olive oil administered (p.o.) for 4 weeks	Attenuated proinflammation cytokine production	STAT3	Han et al. (2019)
	LPS-induced BV2 cell line model	5, 10, or 20 μM astaxanthin for 3 h before LPS addition	Attenuated LPS-induced neuroinflammation
	LPS-induced mouse model	25 mg/kg/day astaxanthin emulsion administered intragastrically for 37 days	Attenuated proinflammation cytokine production	Unclear	Zhao et al. (2021)
	LPS-induced mouse model	40 mg/kg/day astaxanthin administered (p.o.) for 2 weeks	Suppressed microglia activation and attenuated proinflammation cytokine production	miR-31-5p and Notch	Zhou et al. (2021)
	LPS-induced BV2 cell line model	25 μM astaxanthin for 6 h	Attenuated proinflammation cytokine production
	Kaliotoxin-induced mouse model	80 mg/kg astaxanthin administered (p.o.) twice at 1 and 5 h prior to kaliotoxin injection	Attenuated proinflammation cytokine production and BBB disruption	NF-κB	Sifi et al. (2016)
	Tobacco-induced mouse model	40 or 80 mg/kg astaxanthin in olive oil administered (p.o.) once per day for 10 days	Attenuated proinflammation cytokine production	MAPK	Yang et al. (2019)
	LPS-induced Rat microglia	10–500 μM astaxanthin dissolved in DMSO for 48 h	Attenuated proinflammation cytokine production	ATP-P2X7RSignal	Wang et al. (2020b)
	Lanthanum oxide nanoparticle-induced mouse model	60 mg/kg/day astaxanthin in olive oil administered intragastrically for 30 days	Attenuated proinflammation cytokine production	Nrf2	Yuan et al. (2020)
	LPS-induced BV2 cell line model	2–10 μM astaxanthin for 4 h	Attenuated proinflammation cytokine production	NF-κB	Wen et al. (2017)