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AAPS PharmSciTech. 2006 March; 7(1): E64–E71.
Published online 2006 February 3. doi:  10.1208/pt070110
PMCID: PMC2750717

Evaluation of functional stability of quercetin as a raw material and in different topical formulations by its antilipoperoxidative activity


The present study evaluates the antioxidant activity of the flavonol quercetin, and its functional stability as a raw material and when added in formulations. The iron-chelating activity was determined using the bathophenanthroline assay, and the functional stability was evaluated with the antilipoperoxidative assay. Raw material presented concentration-dependent antilipoperoxidative and iron-chelating activities. The initial antilipoperoxidative activity of the raw material, cream and gel-cream were 63%, 78%, and 69%, respectively. There was no detectable loss of activity during 182 days (6 months) of storage at all tested temperatures (4°C, room temperature [RT], 37°C, and 45°C) for the raw material. Considering the method variability of 10%, activity loss greater than 10% for nonionic cream was detected after 126 days at 4°C (20.1%), decreasing thereafter to 22.2% after 182 days. At 45°C, the loss of activity started after 182 days (13.2%). For the anionic gel-cream, activity loss started after 84 days (28.4%, 45°C), decreasing after 182 days to 40.3% at 45°C. At 37°C, activity loss was detected after 182 days (12%). In conclusion, the results suggest that the activity of quercetin depends on iron chelation, and its posible usefulness as a topical antioxidant to prevent oxidative stress-induced skin damage depends on maintaining its antilipoperoxidative activity stored at RT, which avoids special storage conditions.

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Selected References

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1. Fuchs J, Packer L. Photooxidative stress in skin. In: Sies H, editor. Oxidative Stress: Oxidants and Antioxidants. London, UK: Academic Press; 1991. pp. 559–583.
2. Darr D, Fridovich I. Free radicals in cutaneous biology. J Invest Dermatol. 1994;102:671–675. doi: 10.1111/1523-1747.ep12374036. [PubMed] [Cross Ref]
3. Saija A, Tomaino A, Trombetta D, Giacchi M, De Pasquale A, Bonina F. Influence of different penetration enhancers on in vitro skin permeation and in vivo photoprotective effect of flavonoids. Int J Pharm. 1998;175:85–94. doi: 10.1016/S0378-5173(98)00259-2. [Cross Ref]
4. Rieger MM. Oxidative reactions in and on skin: mechanism and prevention. Cosmet Toil. 1993;108:43–56.
5. Aruoma OI. Free radicals, antioxidants and international nutrition. Asia Pac J Clin Nutr. 1999;8:53–63. doi: 10.1046/j.1440-6047.1999.00036.x. [PubMed] [Cross Ref]
6. Bonina F, Lanza M, Montenegro L, et al. Flavonoids as potential protective agents against photo-oxidative skin damage. Int J Pharm. 1996;145:87–94. doi: 10.1016/S0378-5173(96)04728-X. [Cross Ref]
7. Santos AC, Uyemura SA, Lopes JL, Bazon JN, Mingatto FE, Curti C. Effect of naturally occurring flavonoids on lipid peroxidation and membrane permeability transition in mitochondria. Free Radic Biol Med. 1998;24:1455–1461. doi: 10.1016/S0891-5849(98)00003-3. [PubMed] [Cross Ref]
8. van Acker SABE, van Balen GP, van der Berg D-J, Bast A, van der Vijgh WJF. Influence of iron chelation on the antioxidant activity of flavonoids. Biochem Pharmacol. 1998;56:935–943. doi: 10.1016/S0006-2952(98)00102-6. [PubMed] [Cross Ref]
9. Morel I, Lescoat G, Cogrel P, et al. Antioxidant and iron-chelation activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem Pharmacol. 1993;45:13–19. doi: 10.1016/0006-2952(93)90371-3. [PubMed] [Cross Ref]
10. Saija A, Scalese M, Lanza M, Marzullo D, Bonina F, Castelli F. Flavonoids as antioxidant agents: importance of their interaction with biomembranes. Free Radic Biol Med. 1995;19:481–486. doi: 10.1016/0891-5849(94)00240-K. [PubMed] [Cross Ref]
11. Skibola CF, Smith MT. Potential health impacts of excessive flavonoid intake. Free Radic Biol Med. 2000;29:375–383. doi: 10.1016/S0891-5849(00)00304-X. [PubMed] [Cross Ref]
12. Bors W, Heller W, Michel C, Saran M. Flavonoids as antioxidant: determination of radical-scavenging efficiencies. Methods Enzymol. 1990;186:343–355. [PubMed]
13. Lemanska K, Szymusiak H, Tyrakowka B, Zielinski R, Soffers AEMF, Rietjens IMCM. The influence of pH on antioxidant properties and the mechanism of antioxidant action of hydroxyflavones. Free Radic Biol Med. 2001;31:869–881. doi: 10.1016/S0891-5849(01)00638-4. [PubMed] [Cross Ref]
14. Middleton E, Kandwami C. The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. In: Harborne JB, editor. The Flavonoids, Advances in Research Since 1986. Cambridge, UK: Chapman and Hall; 1994. pp. 619–652.
15. Jager A, Wälti M, Neftel K. Side-effects of flavonoids in medical practice. In: Cody V, Middleton E, Harborne JB, Beretz A, editors. Plant Flavonoids in Biology and Medicine II: Biochemical, Cellular, and Medicinal Properties. New York, NY: Alan R. Liss; 1988. pp. 379–394.
16. Wessels P, Holz M, Erni F, Krummen K, Ogorka J. Statistical evaluation of stability data of pharmaceutical products for specification setting. Drug Dev Ind Pharm. 1997;23:427–439. doi: 10.3109/03639049709148492. [Cross Ref]
17. Bolann BJ, Ulvik RJ. Release of iron from ferritin by xanthine oxidase: role of the superoxide radical. Biochem J. 1987;243:55–59. [PubMed]
18. Pedersen PL, Greenawalt JW, Reynafarje B, et al. Preparation and characterization of mitochondria and submitochondrial particles of rat liver and liver-derived tissues. Methods Cell Biol. 1978;20:411–481. doi: 10.1016/S0091-679X(08)62030-0. [PubMed] [Cross Ref]
19. Cain K, Skileter DN. Preparation and use of mitochodria in toxicological research. In: Snell K, Mullock B, editors. Biochemical Toxicology. Oxford, UK: IRL Press; 1987. pp. 217–254.
20. Gornal AG, Bardill CJ, David MM. Determination of serum proteins by means of the biuret reaction. J Biol Chem. 1949;177:751–751. [PubMed]
21. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302–310. doi: 10.1016/S0076-6879(78)52032-6. [PubMed] [Cross Ref]
22. Kowaltowski AJ, Castilho RF, Grijalba MT, Bechara EJ, Vercesi AE. Effect of inorganic phosphate concentration on the nature of inner mitochondrial membrane alterations mediated by Ca2+ ions: a proposed model for phosphate-stimulated lipid peroxidation. J Biol Chem. 1996;271:2929–2934. doi: 10.1074/jbc.271.6.2929. [PubMed] [Cross Ref]
23. Rodrigues T, Santos AC, Pigoso AA, Mingatto FE, Uyemura SA, Curti C. Thioridazine interacts with the membrane of mitochondria acquiring antioxidant activity toward apoptosis—potentially implicated mechanisms. Br J Pharmacol. 2002;136:136–142. doi: 10.1038/sj.bjp.0704672. [PMC free article] [PubMed] [Cross Ref]
24. Klein K. Improving emulsion stability. Cosmet & Toilet. 1984;99:121–126.
25. Yen GC, Chen HY. Antioxidant activity of various tea extracts in relation to their antimutagenicity. J Agric Food Chem. 1995;43:27–32. doi: 10.1021/jf00049a007. [Cross Ref]
26. Laughton MJ, Halliwell B, Evans PJ, Hoult JR. Antioxidant and pro-oxidant actions of the plant phenolics quercetin, gossypol and myricetin: effects on lipid peroxidation, hydroxyl radical generation and bleomycin-dependent damage to DNA. Biochem Pharmacol. 1989;38:2859–2865. doi: 10.1016/0006-2952(89)90442-5. [PubMed] [Cross Ref]
27. Montenegro L, Bonina F, Rigano L, Giogilli S, Sirigu S. Protective effect evaluation of free radical scavengers on UVB induced human cutaneous erythema by skin reflectance spectrophotometry. Int J Cosmet Sci. 1995;17:91–103. doi: 10.1111/j.1467-2494.1995.tb00113.x. [PubMed] [Cross Ref]
28. Singh S. Drug stability testing and shelf-life determination according to international guidelines. Pharm Technol. 1999;23:68–88.
29. Idson B. Stability Testing of Emulsions. Austin, TX: DCI; 1993. pp. 27–30.
30. Minotti G, Aust S. The role of iron in oxygen radical mediated lipid peroxidation. Chem Biol Interact. 1989;71:1–19. doi: 10.1016/0009-2797(89)90087-2. [PubMed] [Cross Ref]
31. Sugihara N, Arakawa T, Ohnishi M, Furuno K. Anti- and pro-oxidative effects of flavonoids on metal-induced lipid hydroperoxide-dependent lipid peroxidation in cultured hepatocytes loaded with α-linolenic acid. Free Radic Biol Med. 1999;27:1313–1323. doi: 10.1016/S0891-5849(99)00167-7. [PubMed] [Cross Ref]
32. Erden Inal M, Kahraman A. The protective effect of flavonol quercetin against ultraviolet: an induced oxidative stress in rats. Toxicology. 2000;154:21–29. doi: 10.1016/S0300-483X(00)00268-7. [PubMed] [Cross Ref]
33. Arora A, Nair MG, Strasburg GM. Structure-activity relationships for antioxidant activities of a series of flavonoids in a liposomal system. Free Radic Biol Med. 1998;24:1355–1363. doi: 10.1016/S0891-5849(97)00458-9. [PubMed] [Cross Ref]
34. Carstensen JT. Disperse and aggregated systems. In: Carstensen JT, editor. Drugs Stability: Principles and Practices. New York, NY: Marcel Dekker Inc; 1995. pp. 172–175.
35. Quality Assurance of Pharmaceuticals: A Compendium of Guidelines and Related Materials. Geneva, Switzerland: World Health Organization; 1997.

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