Oral Absorption And Antioxidant Activity Of Natural Antioxidants

With aging of people and deterioration of environment,our body accumulates more free radicals,which will damage biomolecules such as DNA,proteins and lipids.It has been reported that overproduced free radicals in our body are related to various diseases.Some clinical trials showed that administrating antioxidants could modulate the level of free radicals in our body.However,some natural antioxidants have poor water solubility and low oral bioavailability,restricting their applications in food supplements and drugs.Currently,many natural antioxidants have been developed into antioxidant food supplements.However,many of the products lack effective in vivo antioxidant verifications.We chose hesperetin as a model compound of hydrophobic antioxidants,and tried to improve its oral absorption by increasing its water solubility.Two nano-based formulations were developed,namely hesperetin-TPGS(D-a-tocopheryl polyethylene glycol 1000 succinate)micelles and hesperetin-phosphatidylcholine(PC)complexes.These two formulations were prepared by a simple technique called solvent dispersion,using Food and Drug Administration(FDA)-approved pharmaceutical excipients.Based on the solubility enhancement,the final ratio of hesperetin to TPGS and hesperetin to PC were 1:12(w/w),respectively.As a result,the solubility was increased to 21.5-and 20.7-fold.The hesperetin-TPGS micelles had a small particle size of 26.15 nm,whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm.In addition,the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes enhanced the antioxidant activity of hesperetin to 4.2-and 3.9-fold,respectively.Importantly,the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the area under the concentration-time curve(AUC)of hesperetin after oral administration to 16.2-fold(53.01 h ?g/mL v.s.3.28 h ?g/mL)and 18.0-fold(59.13 ?p,g/mL 3.28 h ?g/mL),respectively.The peak plasma concentration(Cmax)was also increased from 2.64 ?g/mL to 20.67 ?g/mL and 33.09 ?g/mL,respectively.The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin,indicating these formulations' potential of applications in drugs and healthcare products.Upon reception of entrustment from a healthcare related company in Shanghai,we developed antioxidant food supplements with in vivo antioxidant activity.Two formulas were designed based on the physical and chemical properties,oral absorption of natural antioxidants and the relevant regulations.Formula A and formula B both include a tablet containing water-soluble antioxidants such as ingredient 2,vitamin C,proanthocyanidins and hydroxytyrosol,and a soft capsule containing lipid-soluble antioxidants such as ingredient 5,ingredient 4 and vitamin E.We compared the in vivo antioxidant activities of formula A and formula B with the commercially available product C(top food supplement in Japan)using an ethanol induced oxidative damage mice model.Formula A showed a better antioxidant activity than formula B and product C.Oral administration of Formula A for 7 days increased the concentration of reduced glutathione(GSH)in the blood of mice to normal level.The GSH level of the mice administrated with formula B and product C showed no significant differences compared with the model group.Therefore,the effective in vivo antioxidant activity of formula A makes it probable to be developed as an antioxidant dietary supplement.