Kojic acid

J Pharm Pharmacol. 1994 Dec;46(12):982-5.

Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor of catecholase activity of tyrosinase.[Pubmed: 7714722]

METHODS AND RESULTS:
It was found that Kojic acid, which is used in cosmetics for its excellent whitening effect, inhibits catecholase activity of tyrosinase in a non-classical manner. A decrease in the initial velocity to a steady-state inhibited velocity can be observed over a few minutes. This time-dependence, which is unaltered by prior incubation of the enzyme with the inhibitor, is consistent with a first-order transition.
CONCLUSIONS:
The kinetic data obtained correspond to those for a postulated mechanism that involves the rapid formation of an enzyme inhibitor complex that subsequently undergoes a relatively slow reversible reaction. Kinetic parameters characterizing this type of inhibition were evaluated by means of nonlinear regression of product accumulation curves.

Toxicol Sci. 2004 Sep;81(1):43-9.

Enhancement of hepatocarcinogenesis by kojic acid in rat two-stage models after initiation with N-bis(2-hydroxypropyl)nitrosamine or N-diethylnitrosamine.[Pubmed: 15201437]

Kojic acid (KA) has been used as a food additive for preventing enzymatic browning of crustaceans and as a cosmetic agent for skin whitening.
METHODS AND RESULTS:
In the present experiments, effects of KA on the induction of hepatic pre-neoplastic lesions in N-bis(2-hydroxypropyl)nitrosamine-initiated (experiment 1) and non-initiated (experiment 2) models, and its promoting influence in a medium-term liver bioassay (experiment 3) were investigated at dietary doses of up to 2% in male F344 rats. In experiment 1, 2% KA feeding induced significant increases in numbers (22.3 +/- 13.0 vs 8.5 +/- 3.4 in the 0%) and areas (0.37 +/- 0.29 vs 0.05 +/- 0.03 in the 0%) of glutathione-S-transferase P form (GST-P)-positive foci and toxic changes such as vacuolation of hepatocytes and microgranulomas. The development of GST-P-positive foci was pronounced in the animals with hepatocellular toxic changes. In experiment 2, numbers (0.65 +/- 0.57 vs 0.17 +/- 0.28 in the 0%) and areas (0.005 +/- 0.005 vs 0.0007 +/- 0.0012 in the 0%) of GST-P-positive foci and hepatocellular proliferating cell nuclear antigen (PCNA) expression (3.8 +/- 2.3 vs 2.6 +/- 0.7 in the 0%) were significantly increased by the 2% treatment. The PCNA-positive hepatocytes were abundantly localized around the vacuolated and granulomatous legions in both experiments 1 and 2. In experiment 3, significant increases in numbers (16.9 +/- 3.2 vs 8.4 +/- 2.7 in the 0%) and areas (1.62 +/- 0.39 vs 0.77 +/- 0.34 in the 0%) of GST-P-positive foci were again observed with 2% KA.
CONCLUSIONS:
These results demonstrate tumor-promoting and possible hepatocarcinogenic activity of KA at 2%, but the carcinogenic potential is likely to be weak. This study also indicated that enhanced replication of hepatocytes related to toxic changes might be involved as an underlying mechanism.

Journal of Agricultural & Food Chemistry, 1991 , 39 (8) :1396-401.

Inhibitory effect of kojic acid on some plant and crustacean polyphenol oxidases.[Reference: WebLink]

Kojic acid exhibited a competitive inhibition for the oxidation of chlorogenic acid and catechol by potato polyphenol oxidase (PPO) and of 4-methylcatechol and chlorogenic acid by apple PPO.
METHODS AND RESULTS:
This compound showed a mixed-type inhibition for white shrimp, grass prawn, and lobster PPO when DL-beta-3,4-dihydroxyphenylalanine (DL-dopa) and catechol were used as substrates but a mixed-type and a competitive inhibition for mushroom PPO when DL-dopa and L-tyrosine were used, respectively. Potato and apple PPOs were shown to have much higher affinities for Dopa than for chlorogenic acid, 4-methylcatechol, and catechol.
CONCLUSIONS:
These two PPOs also had a higher affinity for Dopa than the other four PPOs. Kojic acid is thus an effective inhibitor of PPO on the oxidation of Dopa.

Arch Pharm Res. 2003 Jul;26(7):532-4.

Gamma-pyrone derivatives, kojic acid methyl ethers from a marine-derived fungus Alternaria [correction of Altenaria] sp.[Pubmed: 12934644]

Kojic acid dimethyl ether (1), and the known Kojic acid monomethyl ether (2), Kojic acid (3) and phomaligol A (4) have been isolated from the organic extract of the broth of the marine-derived fungus Alternaria sp. collected from the surface of the marine green alga Ulva pertusa.
METHODS AND RESULTS:
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.

Saudi Med J. 2009 Apr;30(4):490-3.

Radioprotective effects of kojic acid against mortality induced by gamma irradiation in mice.[Pubmed: 19370273]

To evaluate the protective effects of Kojic acid on mortality induced by gamma irradiation in mice. The efficacy was compared with amifostine as a reference radioprotector.
METHODS AND RESULTS:
This experimental study was conducted in the Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari and Babolsar Radiotherapy Hospital, Babolsar, Iran, between October 2006 and January 2008. Kojic acid was administrated subcutaneously as single doses of 142, 175, 232, and 350 mg/kg, one hour prior to a lethal dose of gamma irradiation (8 Gy). Amifostine was injected subcutaneously at a dose of 200 mg/kg at a similar irradiation dose. The mortality was recorded 30 days after irradiation. The antioxidant activity of the Kojic acid was assessed using the 1, 1-diphenyl-2-picrylhydrazyl free stable radical (DPPH) method. One hundred and twenty NMRI mice were divided into 6 groups with 20 mice in each group. At 30 days after treatment, the percentage of survival in each group was: control, 5%; 142 mg/kg, 5%; 175 mg/kg, 0%; 232 mg/kg, 30%; 350 mg/kg, 40%; and amifostine, 40% one hour treatment prior gamma irradiation. The survival rate was statistically increased in animals treated with Kojic acid (350 mg/kg), one hour prior irradiation, as compared with the irradiated control group.
CONCLUSIONS:
Kojic acid exhibited concentration-dependent scavenging activity on DPPH possessing strong antioxidant activity.