The depigmenting effect of kojic acid esters synthesized by the esterification of kojic acid usingRhizomucor mieheiimmobilized lipase was investigated in B16F1 melanoma cells. The depigmenting effect of kojic acid and kojic acid esters was evaluated by the inhibitory effect of melanin formation and tyrosinase activity on alpha-stimulating hormone- (α-MSH-) induced melanin synthesis in B16F1 melanoma cells. The cellular tyrosinase inhibitory effect of kojic acid monooleate, kojic acid monolaurate, and kojic acid monopalmitate was found similar to kojic acid at nontoxic doses ranging from 1.95 to 62.5 μg/mL. However, kojic acid monopalmitate gave slightly higher inhibition to melanin formation compared to other inhibitors at doses ranging from 15.63 to 62.5 μg/mL. Kojic acid and kojic acid esters also show antioxidant activity that will enhance the depigmenting effect. The cytotoxicity of kojic acid esters in B16F1 melanoma cells was significantly lower than kojic acid at high doses, ranging from 125 and 500μg/mL. Since kojic acid esters have lower cytotoxic effect than kojic acid, it is suggested that kojic acid esters can be used as alternatives for a safe skin whitening agent and potential depigmenting agents to treat hyperpigmentation.

Red palm oil (RPO) is a natural source of Vitamin E (70–80% tocotrienol). It is a potent natural antioxidant that can be used in skin-care products. Its antioxidant property protects skin from inflammation and aging. In our work, a tocotrienol-rich RPO-based nanoemulsion formulation was optimized using response surface methodology (RSM) and formulated using high pressure homogenizer. Effect of the concentration of three independent variables [surfactant (5–15 wt%), co-solvent (10–30 wt%) and homogenization pressure (500–700 bar)] toward two response variables (droplet size, polydispersity index) was studied using central composite design (CCD) coupled to RSM. RSM analysis showed that the experimental data could be fitted into a second-order polynomial model and the coefficients of multiple determination (R²) is 0.9115. The optimized formulation of RPO-based nanoemulsion consisted of 6.09 wt% mixed surfactant [Tween 80/Span 80 (63:37, wt)], 20 wt% glycerol as a co-solvent via homogenization pressure (500 bar). The optimized tocotrienol-rich RPO-based nanoemulsion response values for droplet size and polydispersity index were 119.49nm and 0.286, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM, thus the optimized compositions have the potential to be used as a nanoemulsion for cosmetic formulations.

Members of Bacillaceae family are of major interest in medical industry due to vast antimicrobial peptides they produce as therapeutic agents. For decades, synthetic and natural occurring antibiotics have been used to treat infectious diseases, but heavy dependence on these drugs has led to significant drawbacks which propel continuous development of new antibiotics generation. Recent findings have shown several bacteriocins of Bacillaceae as promising alternatives to the conventional drugs to combat the emergence of new drug-resistant pathogens. In this present review, Bacillaceae bacteriocins’ classification such as lantibiotics and thiazole/oxazole-modified microcins as well as their biochemical characterization such as sensitivity to enzymes, temperature, pH and chemicals are described. This article enlightens on the medical application of several Bacillaceae bacteriocins emphasizing those that underwent and on-going preclinical trials. This review also discusses the development of Bacillaceae bacteriocins production, focusing strains selection and fermentation factors such as inocula size, medium (carbon, nitrogen, minerals sources), temperature, pH, agitation and aeration rate, dissolved oxygen tension (DOT), fermentation time, inducers and mode of operation via various statistical methods for their optimization. It also highlights recent advance in the production of bioengineered and recombinant bacteriocins in bioreactors system which are rarely disclosed in literature.

For years, clinical studies involving human volunteers and several known pre-clinical in vivo models (i.e., mice, guinea pigs) have demonstrated their reliability in evaluating the effectiveness of a number of depigmenting agents. Although these models have great advantages, they also suffer from several drawbacks, especially involving ethical issues regarding experimentation. At present, a new depigmenting model using zebrafish has been proposed and demonstrated. The application of this model for screening and studying the depigmenting activity of many bioactive compounds has been given great attention in genetics, medicinal chemistry and even the cosmetic industry. Depigmenting studies using this model have been recognized as noteworthy approaches to investigating the antimelanogenic activity of bioactive compounds in vivo. This article details the current knowledge of zebrafish pigmentation and its reliability as a model for the screening and development of depigmenting agents. Several methods to quantify the antimelanogenic activity of bioactive compounds in this model, such as phenotype-based screening, melanin content, tyrosinase inhibitory activity, other related proteins and transcription genes, are reviewed. Depigmenting activity of several bioactive compounds which have been reported towards this model are compared in terms of their molecular structure and possible mode of actions. This includes patented materials with regard to the application of zebrafish as a depigmenting model, in order to give an insight of its intellectual value. At the end of this article, some limitations are highlighted and several recommendations are suggested for improvement of future studies.

In this study, 7-O-kojic acid monopalmitate (7-O-KAP) was synthesized using palmitic acid and kojic acid where the yield and biological activities were analyzed. The highest yield of 7-O-KAP (43%) can be obtained at molar ratio of 1:1, enzyme loading of 5% (w/v), temperature of 70 °C, using immobilized lipase N435 in solvent-free system. Stirred tank reactor (STR) provides better mixing of the substrates and biocatalyst with better yield of 7-O-KAP, compared to fluidized tank reactor (FTR) and packed bed reactor (PBR). The 7-O-KAP exhibited pseudoplastic behavior with flow behavior index (n) being less than 1. The 7-O-KAP showed better depigmenting activity with the reduction of melanin content in Danio rerio embryo to 18.70%, significantly lower than the positive control, kojic acid (60.39%) at highest concentration tested (250 μg/mL). Intracellular tyrosinase in Danio rerio embryo was also reduced when treated with 7-O-KAP (12.53%), compared to kojic acid (37.36%) at concentration of 250 μg/mL. In FRAP assay, 7-O-KAP had antioxidant activity of 8156 AAE/mL, which was higher than kojic acid (6794 AAE/mL) at concentration of 2 mg/mL. The 7-O-KAP also reduced peroxidation activity to 12.21%, which was better compared to kojic acid (31.68%) at 2 mg/mL. Moreover, it was found that lipid peroxidation activity of 7-O-KAP (12.21%) was comparable to BHT (11.56%) at 2 mg/mL. Based on this study, 7-O-KAP could be an alternative compound for whitening agent and antioxidant compared to kojic acid and BHT, respectively.