Anti-Inflammatory Effects of Different Astaxanthin Isomers and the Roles of Lipid Transporters in the Cellular Transport of Astaxanthin Isomers in Caco-2 Cell Monolayers.

The anti-inflammatory effects and cellular transport mechanisms of all- E-astaxanthin and its 9Z- and 13Z-isomers were investigated in a Caco-2 cell monolayer model. All three astaxanthin isomers at 1.2 μM significantly reduced the TNF-α-induced secretion of IL-8 by 22-27%. Z-Astaxanthins, especially 9 Z-astaxanthin exhibited greater anti-inflammatory effect than all- E-astaxanthin by down-regulating pro-inflammatory cytokines COX-2 and TNF-α gene expression to 0.88 ± 0.01-fold and 0.83 ± 0.17-fold that of the negative control (NC), respectively. The anti-inflammatory effects of astaxanthin isomers were achieved via modulating the NF-κB signaling pathway as they down-regulated TNF-α-induced phosphorylation of IκBα from 5.3 ± 0.19-fold to 3.8 ± 0.33-4.5 ± 0.27-fold of NC. The scavenger receptor class B type I protein (SR-BI) was found to facilitate the cellular uptake of astaxanthin isomers. Its inhibitor (BLT-1) and antibody (Anti-SRBI) significantly reduced cellular uptake efficiency of all- E-astaxanthin (18.9% and 16.7%, respectively) and 13Z-astaxanthin (28.8% and 30.2%, respectively), but not of 9Z-astaxanthin. The molecular docking experiment showed that 13 Z-astaxanthin had significantly higher affinity with SR-BI (atomic contact energy: -420.31) than all- E-astaxanthin and 9 Z-astaxanthin, which at least partially supports the higher bioavailability of 13 Z-astaxanthin observed in vivo by others.