• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.4
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• pp.454-459
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• 1992

Kojic acid, a fungal metabolite produced by some species of Aspergillus and Penicillium, was found to induce chromosomal aberrations in Chinese hamster ovary cells in the presence or absence of the rat liver homogenate (59 mix). All categories of chromosomal aberrations increased with increased doses of kojic acid. Based on the this result, kojic acid was assumed to be a kind of mutagens. On the potential toxicity of this compound it becomes evident that kojic acid would not be used as a food additive at this time.

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.1
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• pp.72-79
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• 2006

Kojic acid production by Aspergillus flavus strain S44-1 using sucrose as a carbon source was carried out in a 250-mL shake flask and a 2-L stirred tank fermenter. For comparison, production of kojic acid using glucose, fructose and its mixture was also carried out. Kojic acid production in shake flask fermentation was 25.8 g/L using glucose as the sole carbon source, 23.6 g/L with sucrose, and 6.4 g/L from fructose. Reduced kojic acid production (13.5 g/L) was observed when a combination of glucose and fructose was used as a carbon source. The highest production of kojic acid (40.2 g/L) was obtained from 150 g/L sucrose in a 2 L fermenter, while the lowest kojic acid production (10.3 g/L) was seen in fermentation using fructose as the sole carbon source. The experimental data from batch fermentation and resuspended cell system was analysed in order to form the basis for a kinetic model of the process. An unstructured model based on logistic and Luedeking-Piret equations was found suitable to describe the growth, substrate consumption, and efficiency of kojic acid production by A. flavus in batch fermentation using sucrose. From this model, it was found that kojic acid production by A. flavus was not a growth-associated process. Fermentation without pH control (from an initial culture pH of 3.0) showed higher kojic acid production than single-phase pH-controlled fermentation (pH 2.5, 2.75, and 3.0).

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.532-534
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• 2003

Kojic acid dimethyl ether (1), and the known kojic acid mono methyl ether (2), kojic acid (3) and phomaligol A (4) have been isolated from the organic extract of the broth of the marine-derived fungus Altenaria sp. collected from the surface of the marine green alga Ulva pertusa. The structures were assigned on the basis of comprehensive spectroscopic analyses. Each isolate was tested for its tyrosinase inhibitory activity. Kojic acid (3) was found to have significant tyrosinase inhibitory activity, but compounds 1, 2, and 4 were found to be inactive.

• Mycobiology
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• v.31 no.4
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• pp.248-250
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• 2003

Kojic acid was investigated for its antifungal activity against the human pathogenic fungi including Candida albicans, Cryptococcus neoformans and Trichophyton rubrum. For C. albicans, C. neoformans and T. rubrum, the MIC(minimum inhibitory concentration) of kojic acid was 640, 80 and 160 ${\mu}g/ml$, respectively. In C. neoformans, melanin-producing yeast, kojic acid-treated nonmelanized cell was more susceptible to magainin than melanized cell, suggesting melanin give a protective function against microbial peptide.

• YAKHAK HOEJI
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• v.43 no.1
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• pp.28-32
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• 1999

Four derivatives of kojic acid were synthesized and their inhibitory activities against tyrosinase were evaluated. The C-2 hydroxymethyl and C-7 hydroxyl of kojic acid were replaced by carboxylate and amine, respectively. These derivatives were coupled to L-phenylalanine, producing two amide compounds. The carboxylate derivative (3), its amide compound (5), and the amine derivative (7) were weak inhibitors. The amide compound (9) where amine derivative (7) coupled to L-phenylalanine showed strong inhibitory activity ($IC_{50}=24.6{\;}{\mu}M$) comparable to kojic acid.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.3 s.47
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• pp.409-414
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• 2004

Kojic acid is well known for its anti-pigmentation effect with tyrosinase inhibition activity. However, kojic acid is a unstable compound. In order to improve stability, kojic acid derivative, kojic acid $6-O-2',3',4',6'-tetraacetyl-{\beta}-D-glucopy-ranoside\;(KTGP)$, was synthesized with $O-pentaacetyl-{\beta}-D-glucose$ through the regio- and stereo-selective glycosylation of 6-OH group of kojic acid. High yield $(80\%)$ was obtained by the use of Lewis acid and organic base in nonpolar solvent. Hydrolysis of KTGP with the aid of sodium methoxide in methanol afforded kojic acid $6-O-{\beta}-D-glucopyranoside$ (KGP), which was confirmed by $^1H-NMR\;and\;^{13}C-NMR$ KGP is freely soluble in water and soluble in methanol and ethanol. Inhibition activity of KGP for tyrosinase was investigated by measuring the activity of mushroom tyrosinase compared with those of ascorbic acid, kojic acid, and arbutin. The free radical-scavenger activity was determined by the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) assay. In toxicity assay, KGP was much less toxic than kojic acid and arbutin, Therefore, glycosylation of kojic acid may be useful for the development of stable kojic acid derivatives.

• Korean Journal of Food Science and Technology
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• v.14 no.3
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• pp.265-270
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• 1982

An attempt was made to investigate the antioxidant activity of maltol, kojic acid, levulinic acid, furfural, 5-hydroxymethyl furfural (5-HMF), and pyrazine which had been known to be important intermediates of Maillard browning reactions. The activity of these compounds was determined by comparing induction periods of soybean oil substrates containing each compound at a 0.01M level with that of a control. The induction period was arbitrarily taken as the time in hours for a substrate to reach a peroxide value of 60meq/kg oil. The substrates and control were stored at $45.0{\pm}1.0^{\circ}C$ for 30 days. The induction periods of the control, kojic acid, furfural, 5-HMF, maltol, levulinic acid, and pyrazine were respectively 468, 592, 510, 498, 486, 450, and 402 hours. Kojic acid demonstrated considerable antioxidant activity, whereas furfural, 5-HMF, and maltol showed weak activivity. Pyrazine and levulinic acid showed pro-oxidant activity. Although the prooxidant activity of pyrazine seemed definite, that of levulinic acid appeared very weak.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.719-732
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• 2003

A kojic acid derivative, kojic acid 7-O-$\beta$-D-tetraacetylglucopyranoside(KTG) was synthesized. Regio-and stereo-selective glycosylation at 7-postion in kojic acid with $\beta$-D-pentaacetylglucose was achieved with high yield(80％) by the use of Lewis acid and organic base in nonpolar solvent. KTG was hydrolyzed in methanol by the aid of sodium methoxide to give kojic acid 7-O-$\beta$-D-glucopyranoside(KGP). KGP is freely soluble in water and soluble in methanol and ethanol. Its structure was comfirmed by $^1$H-NMR and $^{13}$ C-NMR. Tyrosinase activity inhibition of KGP was measured with mushroom tyrosinase compared with ascorbic acid, kojic acid and arbutin. KGP showed higher tyrosinase inhibition activity($IC_{50}$/=33.3 $\mu\textrm{g}$/ml) than ascorbic acid(63.2 $\mu\textrm{g}$/ml) and arbutin(91.8 $\mu\textrm{g}$/ml) but lower inhibition activity than kojic acid(8.3 $\mu\textrm{g}$/ml). To test free-radical scavenging activity, we used 1, 1-diphenyl-2-picrylhydrazyl(DPPH) as a free-radical source. Free-radical scavenging activity of KGP was very low($SC_{50}$/>1000 $\mu\textrm{g}$/ml) compared with ascorbic acid($SC_{50}$/=2.68 $\mu\textrm{g}$/ml) and arbutin($SC_{50}$/=180$\mu\textrm{g}$/ml). Melanin formation inhibition of KGP was measured in B16 melanoma, compared with kojic acid, arbutin and Vitamin C. Inhibition activity of KGP for melanin formation was not found within test concentrations.

• YAKHAK HOEJI
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• v.42 no.1
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• pp.39-45
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• 1998

Kojic acid, antimelanogenic agent, has been widely used in cosmetics to lighten the skin color. However, it has skin irritancy and instability against pH, temperature and light. To overcome these problems and optimize the molecular structure of kojic acid (KA), a prodrug, kojic acid monostearate(KMS), has been synthesized to modify the topical drug delivery in the point of sustained release of the parent drug via enzymatic hydrolysis during skin absorption. The prodrug was tested for enzymatic hydrolysis with cytosolic fraction of hairless mouse, skin. From the in vitro skin permeation study through hairless mouse skin, we found that KMS was retained in the skin and generated KA continuously by the skin esterase cleavage. In addition, topical formulations of o/w type creams and polyolprepolymer-containing cream were further tested for whitening effects using in vivo yellow skin guinea pig model.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.29 no.1
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• pp.151-167
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• 2003

Melanin biosynthesis is a human defense mechanism to protect skin from UV irradiation and also determines colors of hair and skin. However, as a interest on skin-whitening increases, researches to prevent pigmentation and hypersynthesis of melanin in skin are being actively in progress. Active components used as a whitening agent in cosmeceuticals are kojic acid, arbutin, vitamin C and hydroquinone. However, until now, because comparison researches among them in the aspect of both melanin formation and cellular toxicity have not been performed, we can't exactly estimate merits and defects of them as a whitening agent. To this end, we performed experiments to compare their effects on cell viability and melanin formation. As a first step, in vitro tyrosinase inhibition assay was done. While kojic acid and hydroquinone showed strong inhibition activities(their IC$\_$50/s are all < 100uM), arbutin and vitamin C showed weak activities. IC$\_$50/s of arbutin and vitamin C are 100uM and 400∼500uM, respectively. In B16BL6 melanoma cells, like in vitro tyrosinase inhibition assay, arbutin and kojic acid showed more strong inhibition effect on melanin synthesis than vitamin C. And unlike arbutin, vitamin C and kojic acid induced cell death at high concentration. Although arbutin showed no cytotoxicity, it has side effect to induce morphological change at high concentration.. In this paper, we suggest both kojic acid and arbutin have stronger ability to inhibit melanogenesis than vitamin C. And they also have side effect, that is, kojic acid induces cell death like vitamin C and arbutin changes cell morphology respectively.