Efficacy and tolerability of a depigmenting gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that targets the biological processes regulating skin melanogenesis.

BACKGROUND: The diverse causes of hyperpigmentation and complex nature of melanogenesis make it a challenge to manage. Current approaches either fail to deliver effective pigmentation control or have undesirable safety profiles that preclude their long-term use. AIMS: To evaluate the capacity of a cosmetic gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, phytic acid, and a mixture of hydroxy acids that was designed to target the biological processes regulating skin melanogenesis to attenuate melanin production in vitro and reduce hyperpigmentation clinically. METHODS: Capacity to reduce melanin production in vitro was determined in melanocyte-containing reconstructed human epidermis (RHEm). Clinical efficacy and skin tolerability following twice daily application were assessed in 35 subjects with slight to moderate facial hyperpigmentation by instrumental (VISIA®-CR, Mexameter®) and clinical (mMASI, clinical score, IGA for hyperpigmentation) evaluation on D14, D28, D56, and D84. Maintenance of pigmentation control was followed up 1 month after cessation of treatment on D112. RESULTS: In RHEm in vitro, melanin production was reduced by 50.0% from baseline (D0) on D14 (p < 0.001) and by 67.0% on D21 (p < 0.001). Clinical reductions from baseline in brown spots count (-9.0%; p < 0.05), brown spots area (-16.7%; p < 0.001), and the melanin index (-11.4%; p < 0.001) were observed within 14 days of use. Statistically significant improvements in all clinical parameters were achieved by D28. By the end of treatment on D84, the number and surface area of brown spots were reduced by 28.4% and 40.3% compared to D0, respectively (p < 0.001, both), the melanin index was reduced by 31.1% (p < 0.001), mMASI was reduced by 63.0% (p < 0.001), and skin luminosity was increased by 79.0% (p < 0.001). IGA was reduced from 2.3 on D0 to 1.3 on D84 (p < 0.001). Improvements to all these parameters were maintained until D112, 1 month after termination of treatment. The product also demonstrated very good skin tolerability. CONCLUSION: A gel serum comprising tranexamic acid, niacinamide, 4-butylresorcinol, and hydroxy acids, designed to target the biological processes regulating skin melanogenesis, demonstrates rapid, robust, and sustained pigmentation control in this cohort.

Skin lightening properties of zerumbone cream: A placebo-controlled study.

OBJECTIVE: Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) in vitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach. METHODS: Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18. RESULTS: Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream. CONCLUSION: ZER demonstrated significant potential as a skin-lightening agent.

The effect of emulgel preparation on the stability of Kojic acid in the topical anti-hyperpigmentation products.

BACKGROUND: The emulgel, a novel drug delivery system, merges emulsion and gel, offering advantages like enhanced stability, precise control over drug release kinetics, and increased drug absorption compared to emulsions alone. Kojic acid (KA) demonstrates potent inhibition of the tyrosinase enzyme, a crucial player in the melanin synthesis pathway. AIMS: The main objective of this experimental study is to formulate KA within an emulgel framework and assess its stability under various environmental conditions. METHODS: One percent of KA emulgel and 1% simple gel, serving as the control product, were supplemented with varying concentrations of sodium metabisulfite (SMBS) for its antioxidant properties. The formulations were segregated into four groups and subjected to diverse maintenance and stress conditions over a three-month period. Monthly evaluations of physicochemical alterations were conducted, initially employing digital photography, followed by the extraction of KA and subsequent quantification of its concentration through high performance liquid chromatography (HPLC). RESULTS: The best formulations for retaining KA among the prepared ones were the 0.25% SMBS KA emulgel and the 0.1% SMBS KA simple gel, capable of retaining 86% and 76% of the initial KA content under stress conditions, respectively (p < 0.0001). CONCLUSIONS: Regarding to this study, ideal storage condition for KA emulgel and simple gel is in the refrigerator temperatures. Moreover, optimal SMBS concentrations for stability enhancement are 0.25% for emulgel and 0.1% for the simple gel. A significant statistical difference was observed between refrigerated emulgel and simple gel in the retention of KA in the presence of optimum concentration of antioxidants (p < 0.0001).

Efficacy and safety of novel topical pigment-correcting regimen with biweekly diamond tip microdermabrasion procedures on facial hyperpigmentation.

BACKGROUND: Facial hyperpigmentation can negatively affect an individual's emotional and psychosocial well-being. AIMS: Assess safety and tolerability of a combination of microdermabrasion (DG) procedures using a novel brightening pro-infusion serum (EC-DG) with a targeted at-home treatment regimen in subjects with mild to severe facial hyperpigmentation, including melasma, post-inflammatory hyperpigmentation, and dark spots. PATIENTS/METHODS: This 12-week, open-label study enrolled 18 subjects (Fitzpatrick skin types I-IV) who underwent 6 in-office DG procedures with EC-DG (one procedure administered biweekly), along with daily topical application of a brightening treatment serum and dark spot cream. End points included change from baseline across multiple skin quality attributes and the Melasma Area and Severity Index (MASI), self-assessment questionnaires, and tolerability assessments. RESULTS: The combination treatment was well tolerated and resulted in significant (p ≤ 0.05) improvements from baseline in radiance, tactile roughness, and moisturization/hydration immediately after the first treatment, in MASI score at day 3, and in overall hyperpigmentation at week 4. Most (94.1%) subjects were satisfied with treatment. CONCLUSIONS: DG procedures using EC-DG combined with a targeted at-home skincare regimen are effective and tolerable for treating facial hyperpigmentation across a broad range of skin types.

Quality assessment of hydroquinone, mercury, and arsenic in skin-lightening cosmetics marketed in Ilorin, Nigeria.

Hydroquinone, Mercury (Hg), and Arsenic (As) are hazardous to health upon long-term exposure. Hydroquinone, Hg, and As were analysed in skin-lightening cosmetics randomly purchased from different cosmetic outlets within the Ilorin metropolis, Nigeria. The amount of hydroquinone in the samples was determined using a UV-spectrophotometry method at 290 nm. Hg and As were quantified using atomic absorption spectrophotometry (AAS). UV-spectrophotometry method validation showed excellent linearity (r2 = 0.9993), with limits of detection (0.75 µg/mL), limits of quantification (2.28 µg/mL), relative standard deviation (0.01-0.35%), and recovery (95.85-103.56%) in the concentration range of 5-50 µg/mL. Similarly, r2, LOD, and LOQ for Hg and As were 0.9983 and 0.9991, (0.5 and 1.0 µg/L) and 1.65 and 3.3 µg/L) respectively. All the samples contained hydroquinone, Hg and As in varying amounts. The amounts of hydroquinone, Hg and As present were in the ranges of 1.9-3.3%, 0.08-2.52 µg/g and 0.07-5.30 µg/g respectively. Only three of the analysed samples contained hydroquinone within the permissible limit of 2.0% w/w in cosmetic products. All the samples analysed contained mercury and arsenic in varying amounts. The need to periodically monitor the levels of hydroquinone, mercury, and arsenic in skin-lightening cosmetics marketed in Nigeria is recommended.

Skin-lightening products and Jordanian women: Beliefs and practice. A cross-sectional study.

BACKGROUND: The use of skin-lightening products (SLPs) among Jordanian women has immensely increased and healthcare professionals have a vital role in raising public awareness of SLPs. The aim of this study is to identify SLPs practices among Jordanian women and their basic knowledge of the agents and the side effects associated with using these products. METHODS: A cross-sectional study conducted during October to December of 2022. Jordanian women above 18 years of age were invited to participate via a survey link. Descriptive statistics were used, and logistic regression was applied to screen for variables affecting the knowledge score of the participants. RESULTS: The mean age of the study participants (n = 384) was 32.04 (SD = 12.678). Results demonstrated that more than half of the participants (n = 193) reported current or past use of SLPs. Additionally, less than one-fifth (18.2%) of the participants (n = 70) reported previously experiencing some side-effects after using SLPs. About 90% of participants thought that these side-effects were caused by the active ingredients in SLPs. Most of the participants were able to identify some of the active ingredients used in SLPs such as Vitamin C (87.8%) and Hydroquinone (62.0%). It was also found that young participants, and those employed, or university students had higher knowledge scores of SLPs' active ingredients, and of their side-effects. CONCLUSION: This study demonstrated that Jordanian women are adequately informed about skin-lightening products. Moreover, the practices revealed an educated pattern of action when obtaining information regarding SLPs. Fundamentally, healthcare providers should be influential in educating consumers on the proper use. Strict guidelines and policies should target the practices concerned with these products.

Phytochemical study of Boswellia dalzielii oleo-gum resin and evaluation of its biological properties.

Boswellia dalzielii is a resin-producing tree endemic to West and Central Africa, used by local populations for various medicinal purposes. In this study, B. dalzielii gum resin was analyzed by GC-MS and UHPLC-MS to identify and quantify volatile and non-volatile compounds. Its main volatile constituents were α-pinene (54.9%), followed by α-thujene (4.4%) and α-phellandren-8-ol (4.0%). Pentacyclic triterpenoids such as ß-boswellic acids and their derivatives were quantified by UHPLC-MS and their content was shown to reach around 22% of the gum resin. Since some of the volatile and non-volatile compounds identified in this work are known to possess biological effects, the bioactivities of B. dalzielii ethanolic extract, essential oil, as well as fractions of the oil and extract were evaluated. Some of these samples exhibited interesting anti-inflammatory properties, and their antioxidant, anti-ageing and skin-bleaching activities were also tested.

Targeting tyrosinase in hyperpigmentation: Current status, limitations and future promises.

Hyperpigmentation is a common and distressing dermatologic condition. Since tyrosinase (TYR) plays an essential role in melanogenesis, its inhibition is considered a logical approach along with other therapeutic methods to prevent the accumulation of melanin in the skin. Thus, TYR inhibitors are a tempting target as the medicinal and cosmetic active agents of hyperpigmentation disorder. Among TYR inhibitors, hydroquinone is a traditional lightening agent that is commonly used in clinical practice. However, despite good efficacy, prolonged use of hydroquinone is associated with side effects. To overcome these shortcomings, new approaches in targeting TYR and treating hyperpigmentation are desperately requiredessentialneeded. In line with this purpose, several non-hydroquinone lightening agents have been developed and suggested as hydroquinone alternatives. In addition to traditional approaches, nanomedicine and nanotheranostic platforms have been recently proposed in the treatment of hyperpigmentation. In this review, we discuss the available strategies for the management of hyperpigmentation with a focus on TYR inhibition. In addition, alternative treatment options to hydroquinone are discussed. Finally, we present nano-based strategies to improve the therapeutic effect of drugs prescribed to patients with skin disorders.

Avaliação da rotulagem de cosméticos clareadores de pele comercializados em Juazeiro, Bahia, Brasil / Evaluation of the labeling of skin lightening cosmetics marketed in Juazeiro, Bahia, Brazil

A hiperpigmentação da pele, principalmente na região facial, resulta em um incômodo estético que afeta a qualidade de vida do indivíduo, levando a busca por produtos clareadores. Este estudo avaliou a conformidade dos rótulos de cosméticos comercializados como "produtos clareadores de pele", bem como a existência de substâncias clareadoras proibidas neste tipo de produto. Foi realizada uma análise transversal descritiva qualitativa no período de abril a maio de 2022, em busca por cosméticos comercializados em estabelecimentos farmacêuticos e lojas de produtos cosméticos localizadas no município de Juazeiro/BA. Foram selecionados 18 produtos e os desvios de rotulagem identificados com base na legislação utilizada vigente à época do estudo, foram: ausência de informações sobre advertências/restrições de uso e número de registro incompleto, equivalente a 16,7% (n = 3) das amostras. A hidroquinona, proibida nesse tipo de produto, foi encontrada em um cosmético (5,5%). Embora a maioria das amostras analisadas esteja em conformidade com as exigências legais, os resultados evidenciam descumprimentos, indicando a necessidade de uma fiscalização mais rigorosa a fim de evitar possíveis danos à saúde do usuário.

Skin hyperpigmentation, particularly in the facial region, can be an aesthetic nuisance that affects an individual's quality of life, leading them to seek out whitening products. This study evaluated the compliance of cosmetics labels marketed as "skin lightening products", and assessed the presence of whitening substances prohibited in this type of product. A qualitative, descriptive, cross-sectional analysis was conducted between April and May 2022 in Juazeiro, Bahia, Brazil, focusing on cosmetics sold in pharmaceutical establishments and cosmetic product stores. Eighteen products were selected, and labeling deviations identified based on the legislation in force at the time of the study. These included a lack of information on warnings/use restrictions and incomplete registration numbers, affecting 16.7% (n = 3) of the samples. Hydroquinone, prohibited in this type of product by the legislation, was detected in one cosmetic (5.5%). Although most of the analyzed samples comply with legal requirements, the observed non-compliance highlights the need for more stringent inspection to prevent potential harm to user's health.

Avaliação da rotulagem de cosméticos clareadores de pele comercializados em Juazeiro, Bahia, Brasil / Evaluation of the labeling of skin lightening cosmetics marketed in Juazeiro, Bahia, Brazil

A hiperpigmentação da pele, principalmente na região facial, resulta em um incômodo estético que afeta a qualidade de vida do indivíduo, levando a busca por produtos clareadores. Este estudo avaliou a conformidade dos rótulos de cosméticos comercializados como "produtos clareadores de pele", bem como a existência de substâncias clareadoras proibidas neste tipo de produto. Foi realizada uma análise transversal descritiva qualitativa no período de abril a maio de 2022, em busca por cosméticos comercializados em estabelecimentos farmacêuticos e lojas de produtos cosméticos localizadas no município de Juazeiro/BA. Foram selecionados 18 produtos e os desvios de rotulagem identificados com base na legislação utilizada vigente à época do estudo, foram: ausência de informações sobre advertências/restrições de uso e número de registro incompleto, equivalente a 16,7% (n = 3) das amostras. A hidroquinona, proibida nesse tipo de produto, foi encontrada em um cosmético (5,5%). Embora a maioria das amostras analisadas esteja em conformidade com as exigências legais, os resultados evidenciam descumprimentos, indicando a necessidade de uma fiscalização mais rigorosa a fim de evitar possíveis danos à saúde do usuário. (AU)

Skin hyperpigmentation, particularly in the facial region, can be an aesthetic nuisance that affects an individual's quality of life, leading them to seek out whitening products. This study evaluated the compliance of cosmetics labels marketed as "skin lightening products", and assessed the presence of whitening substances prohibited in this type of product. A qualitative, descriptive, cross-sectional analysis was conducted between April and May 2022 in Juazeiro, Bahia, Brazil, focusing on cosmetics sold in pharmaceutical establishments and cosmetic product stores. Eighteen products were selected, and labeling deviations identified based on the legislation in force at the time of the study. These included a lack of information on warnings/use restrictions and incomplete registration numbers, affecting 16.7% (n = 3) of the samples. Hydroquinone, prohibited in this type of product by the legislation, was detected in one cosmetic (5.5%). Although most of the analyzed samples comply with legal requirements, the observed non-compliance highlights the need for more stringent inspection to prevent potential harm to user's health. (AU)

Knowledge, perceptions, practices, promotive factors, and health risks awareness of African Basotho women towards skin lightening products: a cross-sectional survey.

Introduction: the use of skin lightening products (SLPs) by women is poorly documented in Africa, with statistics from some countries entirely missing. This study assessed knowledge, perceptions, practices and factors associated with health risk awareness of African Basotho women towards SLPs. Methods: this was a questionnaire-based cross-sectional study based on convenience sampling of females in secondary/high schools, universities, factories and business offices in Maseru City, Lesotho. Analysis of the differences in knowledge (adequate ≥50% score), perceptions, and practices between four participant groups was based on ANOVA, p<0.05. Associations between sociodemographic variables and the use of SLPs were performed using logistic regression model in SPSS version 27. Results: a total of 468 participants out of 496 responders qualified for data analysis based on predefined data cleaning criteria. Knowledge about SLPs was adequate (78.2%, n=468). By proportion, the main sources of the SLPs were supermarkets (67.6%, n=183) and pharmacy stores (41.9%). About 43.7% (n=468) of the participants used SLPs, with the factory workers mostly associated with SLPs use (aOR: 2.91, 95% CI 1.15-7.40; p=0.02). The majority (53.4%, n=131) of users had inadequate knowledge about the link between skin lightening and skin problems. The most common reasons for use of SLPs were rash (pimples, blemishes) (43.9%, n=107), dry skin (41.1%) and skin reddening (33.6%). Conclusion: there was adequate knowledge and moderate practice of skin lightening among African Basotho women. Public awareness campaigns and strict regulations are required to address the problem of SLPs use.

Neurog1-Derived Peptides RMNE1 and DualPep-Shine Penetrate the Skin and Inhibit Melanin Synthesis by Regulating MITF Transcription.

Anti-pigmentation peptides have been developed as alternative skin-lightening agents to replace conventional chemicals that have adverse effects on the skin. However, the maximum size of these peptides is often limited by their low skin and cell penetration. To address this issue, we used our intra-dermal delivery technology (IDDT) platform to identify peptides with hypo-pigmenting and high cell-penetrating activity. Using our cell-penetrating peptides (CPPs) from the IDDT platform, we identified RMNE1 and its derivative RMNE3, "DualPep-Shine", which showed levels of α-Melanocyte stimulating hormone (α-MSH)-induced melanin inhibition comparable to the conventional tyrosinase inhibitor, Kojic acid. In addition, DualPep-Shine was delivered into the nucleus and regulated the gene expression levels of melanogenic enzymes by inhibiting the promoter activity of microphthalmia-associated transcription factor-M (MITF-M). Using a 3D human skin model, we found that DualPep-Shine penetrated the lower region of the epidermis and reduced the melanin content in a dose-dependent manner. Furthermore, DualPep-Shine showed high safety with little immunogenicity, indicating its potential as a novel cosmeceutical ingredient and anti-pigmentation therapeutic agent.

Preclinical studies on melanogenesis proteins using a resveratrol-nanoformula as a skin whitener.

A naturally occurring polyphenol called trans-resveratrol has received a lot of attention due to its possible health advantages for humans. The low solubility of trans-resveratrol and its isomerization upon UV exposure strongly limit its application as a skin-whitening agent. In the present study, to increase trans-resveratrol solubility, a new nanoformula was created by combining hydrophilic surfactants and oils. Trans-Resveratrol nanoformula has been prepared, characterized, and applied as a skin-whitening agent on the dorsal skin of Guinea pigs. The optimized trans-resveratrol nanoformula with a particle size of 63.49 nm displayed a single peak and a polydispersity index [0.36 ± 0.02]. In addition, the zeta potential of the optimized formula was -30.4 mV, confirming the high stability of this nanoformula. The melanin contents in the trans-resveratrol nanoformula-treated group were substantially lower than those of the control and the blank nanoformula-treated groups after staining of the dorsal skins [black areas] of guinea pigs with Fontana Mountain dye. The pigmentation index in the control, blank nanoformula, and optimized trans-resveratrol nanoformula were 329.4 ± 36.9, 335.8 ± 71.4, and 124.8 ± 19.6 respectively. Confirming this finding, immunohistochemistry analysis of skin tissues revealed that the expressions of melanogenesis-regulating proteins such as tyrosinase and microphthalmia-associated transcription factor were down-regulated. The safety of topical application of trans-resveratrol nanoformula was validated by no changes in free radical levels and oxidative stress markers proteins in the livers and kidneys of guinea pigs at the end of the experiment. Conclusions: A novel trans-resveratrol nanoformula as well as the mechanism whereby it promotes skin whitening effects were presented. Furthermore, the study illustrated that trans-resveratrol nanoformula is safe, non-toxic, and can be applied for skin whitening, although more research on human skin is needed.

Potential application of natural bioactive compounds as skin-whitening agents: A review.

BACKGROUND: Melanin is a skin pigment that gives color to the skin, hair, and eyes. The accumulation or over production of melanin can lead to aesthetic problems as well as serious diseases associated with hyperpigmentation. Skin lightening is described as the procedure of using natural or synthetic products to lighten the skin tone or provide an even skin complexion by reducing the amount of melanin in the skin; therefore, skin lightening products help people to treat their skin problems. Ingredients such as hydroquinone, ascorbic acid, and retinoic acid were used as whitening agents to lighten the skin. However, they have many adverse effects on the skin and body health, such as skin irritation. AIM: In this review, firstly, discuss on the directly/indirectly target melanogenesis-related signal pathways. Secondly, summarize potential natural bioactive ingredients with skin lightening properties from plants, marine organisms, microorganisms. Finally, the remaining problems and future challenges are also discussed. METHODS: For relevant literature, a literature search was conducted using Google Scholar and Web of Science. Natural bioactive compounds, tyrosinase inhibitors, and other related topics were researched and evaluated. RESULTS: Natural products isolated from plant and animal resources are potential active cosmetic candidates for lightening the skin tone and skin whitening and protection against UV irradiation. Natural bioactive ingredients as cosmetic whitening additives have attracted increasingly attention due to their safety and cost effectiveness, with few side effects. CONCLUSION: Although natural active substances have been advocated for use in whitening cosmetics in recent years, there are still many challenges due to the fact that traditional inhibitors are used perennial in cosmetics which cannot be easily changed and the research on natural active substances is still in its infancy. In the future, by improving the extraction technique of natural extracts, it is achieved to give a qualitative and quantitative analysis of the active ingredients of the extracts, to determine the effect of the active components of action, and to find the substances that have the best possible whitening effect in natural organisms.

Extraction and Concentration of Waste Pueraria lobata Stems with Antioxidants and Anti-Melanogenesis Activity as a Novel Skin Whitening Agent for Natural Cosmetic Prototypes.

The root of Pueraria lobata (Willd.) is used commercially in different products, including dietary supplements, cosmetics, and teas, but its stem part is rarely used and studied. Therefore, this study evaluated the antioxidant and anti-melanogenesis activities of the bioactive fraction of P. lobata stem and investigated whether the activated carbon decolorization technique would have an impact on its activity and chemical composition. We observed that the dichloromethane fraction of P. lobata stem (DCM-PLS) has excellent antioxidant and anti-melanin synthesis activity at a concentration of 50 µg/mL. For the investigation of the anti-melanogenesis mechanism, we evaluated the mRNA expression of tyrosinase, which was depressed by the DCM-PLS. Daidzin was identified as the main active ingredient in DCM-PLS by using a high-performance liquid chromatography-diode array detector-hyphenated with tandem mass spectrometry. In addition, the activated carbon decolorization technology has no negative impact on the main components and bioactivity of DCM-PLS. DCM-PLS also did not induce any skin response in the human skin safety test. Collectively, DCM-PLS could be used as a natural type of skin-whitening agent in skin care products.

Biological activities and safety data of kojic acid and its derivatives: A review.

Kojic acid presents a variety of applications for human use, especially as a depigmenting agent. Its derivatives are also proposed in order to prevent chemical degradation, prevent adverse effects and improve efficacy. The aim of this study was to peer review the current scientific literature concerning the biological activities and safety data of kojic acid or its derivatives, aiming at human use and trying to elucidate the action mechanisms. Three different databases were assessed, and the word "kojic" was crossed with "toxicity," "adverse effect," "efficacy," "effect," "activity" and "safety." Articles were selected according to pre-defined criteria. Besides the depigmenting activity, kojic acid and derivatives can act as antioxidant, antimicrobial, anti-inflammatory, radioprotector, anticonvulsant and obesity management agents, and present potential as antitumor substances. Depigmenting activity is due to the molecules, after penetrating the cell, binding to tyrosinase active site, regulating melanogenesis factors, leucocytes modulation and free radical scavenging activity. Hence, polarity, size and ligands are also important factors for activity. Kojic acid and derivatives present cytotoxicity to some cancerous cell lines, including melanoma, hepatocellular carcinoma, ovarian cancer, breast cancer and colon cancer. Regarding safety, kojic acid or its derivatives are safe molecules for human use in the concentrations tested. Kojic acid and its derivatives have great potential for cosmetic, pharmaceutical and medical applications.