Carotenoid Stereochemistry Affects Antioxidative Activity of Liposomes Co-encapsulating Astaxanthin and Tocotrienol

• Published in: Chemical & pharmaceutical bulletin Vol. 66; no. 7; pp. 714 - 720
• Main Authors: Ishikawa, Misuzu, Hirai, Shota, Yoshida, Tatsusada, Shibuya, Natsumi, Hama, Susumu, Takahashi, Yu, Fukuta, Tatsuya, Tanaka, Tamotsu, Hosoi, Shinzo, Kogure, Kentaro
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.07.2018; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Absorption spectra; Antioxidants; antioxidation; Astaxanthin; astaxanthin stereoisomer; Chemical bonds; Electron states; Encapsulation; intermolecular interaction; Liposomes; Mathematical analysis; Optimization; Stereochemistry; Stereoisomers; tocotrienol; astaxanthin stereoisomer; antioxidation; tocotrienol; intermolecular interaction
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c18-00035

We previously found that antioxidative activity of liposomes co-encapsulating astaxanthin (Asx) and tocotrienols (T3s) was higher than the calculated additive activity, which results from intermolecular interactions between both antioxidants (J. Clin. Biochem. Nutr., 59, 2016, Kamezaki et al.). Herein, we conducted experiments to optimize Asx/α-T3 ratio for high antioxidative activity, and tried to elucidate details of intermolecular interaction of Asx with α-T3. Higher activity than calculated additive value was clearly observed at an Asx/α-T3 ratio of 2 : 1, despite two α-T3 would potentially interact with two terminal rings of one Asx. The synthetic Asx used in this study was a mixture of three stereoisomers, 3R,3′R-form (Asx-R), 3S,3′S-form (Asx-S) and 3R,3′S-meso form (Asx-meso). The calculated binding energy of the Asx-S/α-T3 complex was higher than those of Asx-R/α-T3 and Asx-meso/α-T3, suggesting that Asx-S and α-T3 is the most preferable combination for the intermolecular interaction. The optimal Asx-S/α-T3 ratio for antioxidation was shown to be 1 : 2. These results suggest that the Asx stereochemistry affects the intermolecular interaction of Asx/α-T3. Moreover, the absorption spectrum changes of Asx-S upon co-encapsulation with α-T3 in liposomes indicate that the electronic state of Asx-S is affected by intermolecular interactions with α-T3. Further, intermolecular interactions with α-T3 affected the electronic charges on the C9, C10 and C15 atoms in the polyene moiety of Asx-S. In conclusion, the intermolecular interaction of Asx/T3 depends on the Asx stereochemistry, and caused a change in the electronic state of the Asx polyene moiety by the presence of double bond in the T3 triene moiety.