Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway

Abstract

Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced β-secretase and Aβ1–42 generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity, neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding.

Pyropia yezoensis Extract Suppresses IFN-Gamma- and TNF-Alpha-Induced Proinflammatory Chemokine Production in HaCaT Cells via the Down-Regulation of NF-κB

“…Carotenoid compounds contribute to light harvesting and photo-protection and have potent antioxidant, anti-inflammatory, and neuroprotective properties [50]. Astaxanthin has been reported to have anti-inflammatory effects with nerve inflammation, gastric inflammation, and heat stress-induced inflammation [51][52][53]. The main sources of astaxanthin are known mainly isolated from natural krill shrimp, lobster, crab, salmon, yeast strains, and marine algae which are abundant in Phaffia rhodozyma and Haematococcus pluvialis.…”

Astaxanthin Protects Against Early Acute Kidney Injury in Severely-Burned Rats Through Inactivating TLR4/MyD88/NF-kB Axis and Upregulating Heme Oxygenase-1

“…In ammation is also the other crucial result following circular or tissue ROS burst after surgery or severe trauma. ATX has been suggested an antiin ammatory role based on several in vivo or in vitro researches referring to neurologic injury/dysfunction/diseases, dermatitis, lung injury, diabetes related disorder, tumor development and so on [55][56][57][58][59][60][61][62][63][64] . In terms of burn injury, we had observed the bene cial effect of ATX to prevent the deterioration of burn-wound through ameliorating tissue in ammation in wounds 65 .…”

Bee Venom Soluble Phospholipase A2 Exerts Neuroprotective Effects in a Lipopolysaccharide-Induced Mouse Model of Alzheimer’s Disease via Inhibition of Nuclear Factor-Kappa B

“…Bee venom sPLA2 was obtained from Inistst Company Limited (Gyeonggi-do, South Korea), dissolved in phosphate-buffered saline (PBS; final concentration: 1 mg/mL) and stored at −20°C until use. The LPS was purchased from Sigma-Aldrich (serotype 0111:B4; Sigma-Aldrich, St. Louis, MO, USA) and was prepared and stored as previously described (Han et al, 2019).…”