Dietary Astaxanthin: A Promising Antioxidant and Anti-Inflammatory Agent for Brain Aging and Adult Neurogenesis

Abstract

Decreased adult neurogenesis, or the gradual depletion of neural stem cells in adult neurogenic niches, is considered a hallmark of brain aging. This review provides a comprehensive overview of the intricate relationship between aging, adult neurogenesis, and the potential neuroregenerative properties of astaxanthin, a carotenoid principally extracted from the microalga Haematococcus pluvialis. The unique chemical structure of astaxanthin enables it to cross the blood-brain barrier and easily reach the brain, where it may positively influence adult neurogenesis. Astaxanthin can affect molecular pathways involved in the homeostasis, through the activation of FOXO3-related genetic pathways, growth, and regeneration of adult brain neurons, enhancing cell proliferation and the potency of stem cells in neural progenitor cells. Furthermore, astaxanthin appears to modulate neuroinflammation by suppressing the NF-κB pathway, reducing the production of pro-inflammatory cytokines, and limiting neuroinflammation associated with aging and chronic microglial activation. By modulating these pathways, along with its potent antioxidant properties, astaxanthin may contribute to the restoration of a healthy neurogenic microenvironment, thereby preserving the activity of neurogenic niches during both normal and pathological aging.

Keywords: FOXO3; NF-κB; Nrf2; adult neurogenesis; aging; astaxanthin; brain.

Figure 1

Potential biochemical pathways induced by astaxanthin that sustain adult neurogenesis. Astaxanthin may promote cell proliferation and improve stem cell potency in NPCs via increased activation of FOXO3, PI3K, and MEK signaling pathways [84]. Moreover, in vivo astaxanthin supplementation increased BDNF levels, a fundamental neurotrophic factor in the growth and survival of new neurons via ERK signaling [85,86]. BDNF = brain-derived neurotrophic factor; CDK = cyclin-dependent kinase; FOXO3 = Forkhead box O3; MEK1/2 = mitogen-activated protein kinase 1/2; mTOR = mammalian target of rapamycin; OCT4 = octamer-binding transcription factor 4; PI3K phosphoinositide 3-kinase; Rac = Ras-related C3 botulinum toxin substrate; Raf = rapidly accelerated fibrosarcoma; SOX2 = sex-determining region Y-box 2; and TrkB = tropomyosin receptor kinase B.

Figure 2

Nrf2-mediated antioxidant mechanism activated by astaxanthin during brain aging. Astaxanthin may decrease Nrf2 proteasomal degradation via the Keap1 pathway. Astaxanthin stimulates Nrf2 nuclear translocation and transcriptional activation of antioxidant genes through the ARE sequences. ARE = antioxidant responsive element; Cul3 = cullin3; GST-1 = glutathione-S-transferase 1; Keap1 = Kelch-like ECH-associated protein 1; HO-1 = heme oxygenase 1; Nrf2 = nuclear factor erythroid 2-related factor 2; and NQO1 = NADPH quinone dehydrogenase 1.

Figure 3

Anti-inflammatory activity of astaxanthin during chronic neuroinflammation. Astaxanthin may effectively reduce microglial-induced neuroinflammation by suppressing the NF-κB pathway and impairing the consequent nuclear translocation and the DNA binding activity of p50/p65 dimers. Cox-2 = cytochrome c oxidase subunit II; IKK = IκB kinase; IL = interleukin; iNOS = inducible nitric oxide synthase; and TNF = tumor necrosis factor.