Functional Properties and Components of Koenigia alpina Extract.

BACKGROUND: Koenigia alpina (All.) T.M.Schust. & Reveal (alpine knotweed) is a perennial herb belonging to the Polygonaceae family. Several studies have examined Polygonaceae species' potential applications as cosmeceutical materials; however, the potential of K. alpina as a cosmeceutical has not yet been studied. MATERIALS AND METHODS: Hydrogen peroxide (H2O2) and lipopolysaccharide were used to induce an inflammatory response in RAW 264.7 cells. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals and H2O2 were used to evaluate the free-radical scavenging activity of K. alpina extract and its protective effect against reactive oxygen species (ROS)-induced cell damage. The whitening, antiaging, and cell proliferation/migration effects of the extracts were evaluated via tyrosinase inhibition, collagenase/elastase inhibition, and wound healing assays, respectively. The anti-inflammatory effect was confirmed by evaluating nitric oxide (NO) production in RAW 264.7 cells. High-performance liquid chromatography (HPLC), UV, and MS/MS were used to determine the main components of the extract and fractions. RESULTS: The ethyl acetate (EA) fraction and its aglycone fraction showed very high free-radical scavenging activities (47.5 and 47.1 µg/mL, respectively). The extract/fractions also showed significant tyrosinase inhibition (IC50 = 0.38 mg/mL in EA fraction), collagenase inhibition (IC50 = 0.21 mg/mL in EA fraction), and elastase inhibition (IC50 = 0.57 mg/mL in aglycone fraction). NO production in lipopolysaccharide-induced RAW 264.7 cells was inhibited by the extract/fractions. The extract also promoted the closure of scratch wounds in HaCaT cells. The K. alpina extract/fractions contained cardamonin, quercetin, and quercitrin. CONCLUSION: K. alpina extracts/fractions showed antioxidant, antiaging, whitening, and anti-inflammatory activities, suggesting they may have potential as antiaging cosmeceuticals.

Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity.

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1-15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC50 value of 0.51 µM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver-Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition.

In Vitro In Silico Screening Strategy and Mechanism of Novel Tyrosinase Inhibitory Peptides from Nacre of Hyriopsis cumingii.

For thousands of years, pearl and nacre powders have been important traditional Chinese medicines known for their skin whitening effects. To prepare the enzymatic hydrolysates of Hyriopsis cumingii nacre powder (NP-HCH), complex enzymatic hydrolysis by pineapple protease and of neutral protease was carried out after the powder was pre-treated with a high-temperature and high-pressure method. The peptides were identified using LC-MS/MS and picked out through molecular docking and molecular dynamics simulations. Subsequently, the tyrosinase inhibitory and antioxidant properties of novel tyrosinase inhibitory peptides were investigated in vitro. In addition, the enzymatic activity of tyrosinase in B16F10 cells as well as melanin content and antioxidant enzyme levels were also examined. The results showed that a tyosinase inhibitory peptide (Tyr-Pro-Asn-Pro-Tyr, YPNPY) with an efficient IC50 value of 0.545 ± 0.028 mM was identified. The in vitro interaction results showed that YPNPY is a reversible competitive inhibitor of tyrosinase, suggesting that it binds to the free enzyme. The B16F10 cell whitening test revealed that YPNPY can reduce the melanin content of B16F10 cells by directly inhibiting the activity of intracellular tyrosinase. Additionally, it indirectly affects melanin production by acting as an antioxidant. These results suggest that YPNPY could be widely used as a tyrosinase inhibitor in whitening foods and drugs.

Nano-vesicular systems for melanocytes targeting and melasma treatment: In-vitro characterization, ex-vivo skin retention, and preliminary clinical appraisal.

Melasma represents an acquired melanogenesis disorder resulting in skin's hyperpigmentation effect. Although several approaches are adopted for melasma treatment, nanotechnology presents the most convenient one. Therefore, the present work aimed to formulate and characterize three nano-vesicular systems namely, liposomes, penetration enhancer containing vesicles (PEVs) and invasomes to enhance the topical delivery of the skin whitening agent; alpha arbutin (α-arbutin) for the treatment of melasma. Liposomes were prepared according to a 23 full factorial design and the selected formula was further employed for the preparation of PEVs and invasomes. Results showed that the three vesicular systems exhibited nano-sizes ranging from 151.95 to 672.5 nm, negative charges ranging from -12.50 to -28.20 mV, high entrapment efficiencies ranging from 80.59 to 99.53 %, good stability and prolonged-release of α-arbutin for 24 h after dispersion in hydrogel form. The deposition study from the vesicular hydrogel confirmed their effectiveness for the drug's accumulation in the skin reaching an average of 1.6-fold higher in the stratum corneum, 1.6-1.8-fold higher in the epidermis, and 1.6-1.8-fold higher in the dermis compared to the free drug dispersion in hydrogel. A preliminary clinical split-face study on patients suffering from melasma revealed that α-arbutin-loaded liposomes and PEVs in hydrogel forms showed better clinical outcomes compared to the free α-arbutin hydrogel as well as to the previously published α-arbutin encapsulated in chitosan nanoparticles and dispersed in hydrogel form. This delineates the aforementioned nano-vesicular systems as effective and clinically superior delivery means for melasma management.

Antioxidant and Skin-Whitening Efficacy of a Novel Decapeptide (DP, KGYSSYICDK) Derived from Fish By-Products.

The skin is vulnerable to damage from ultraviolet rays and oxidative stress, which can lead to aging and pigmentation issues. This study investigates the antioxidant and whitening efficacy of a decapeptide (DP, KGYSSYICDK) derived from marine fish by-products and evaluates its potential as a new skin-whitening agent. DP demonstrated high antioxidant activity, showing comparable or superior performance to Vitamin C (Vit. C) in ferric reducing antioxidant power (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. In hydrogen peroxide (H2O2)-treated HaCaT cells, DP increased cell viability and reduced reactive oxygen species (ROS) generation. Furthermore, DP inhibited tyrosinase activity and decreased melanin production in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 melanoma cells in a dose-dependent manner. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that DP reduces the mRNA expression of MITF, tyrosinase, and MC1R, thus suppressing melanin production. DP exhibits strong binding interactions with multiple amino acid residues of tyrosinase, indicating potent inhibitory effects on the enzyme. These results suggest that DP possesses significant antioxidant and whitening properties, highlighting its potential as a skin-whitening agent. Future research should focus on optimizing DP's structure and exploring structure-activity relationships.

Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?

We present a case of a patient with a 10-year history of blue-black macules and patches on the face and an associated history of skin-lightening cream usage. The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Interestingly, the biopsy did not show characteristic findings of ochronosis, confusing the final diagnosis, however discontinuing the skin-lightening creams halted the progression of the patient's skin lesions supporting a diagnosis of EO. EO presents as asymptomatic hyperpigmentation after using products containing hydroquinone. This condition is most common in Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these populations. Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada. However, with the increased use of skin-lightening creams in certain populations, it is important for dermatologists to accurately recognize the clinical features of exogenous ochronosis to differentiate it from similar dermatoses. An earlier diagnosis can prevent the progression to severe presentations with papules and nodules. We summarize the clinical presentations diagnostic features, and treatment pearls, concluding with a discussion of the differential diagnoses.  J Drugs Dermatol. 2024;23(7):567-568.     doi:10.36849/JDD.8248.

A Patient With Proteinuria, Myalgias, and Decreased Pigmentation of Facial Skin.

A patient had bilateral leg edema, insomnia, myalgias, paresthesias in the fingertips, lighter pigmentation of the facial skin compared with other areas of the body, proteinuria, and an elevated creatinine level. What is the diagnosis and what would you do next?

An update on the safety of hydroquinone.

Hydroquinone has been used for years for multiple conditions, including melasma, post-inflammatory hyperpigmentation, dyschromia from photoaging, and solar lentigines. It is known to be a very effective lightening agent, but several concerns have been raised about this widely used agent. The recent U.S. ban on over-the-counter skin lightening products containing hydroquinone has prompted further questioning of the safety of this widely used agent. While there have been prior informative, large-scale reviews on the safety of hydroquinone, new findings have since been reported. Here, we provide an updated review of studies published in the past 15 years on hydroquinone safety.

An Update on New and Existing Treatments for the Management of Melasma.

Melasma is a chronic, acquired disorder of focal hypermelanosis that carries significant psychosocial impact and is challenging for both the patient and the treating practitioner to manage in the medium to long term. Multiple treatments have been explored, often in combination given the many aetiological factors involved in its pathogenesis. Therapeutic discoveries to treat melasma are a focal topic in the literature and include a range of modalities, with recent developments including updates on visible light photoprotection, non-hydroquinone depigmenting agents, oral tranexamic acid, chemical peels, and laser and energy-based device therapy for melasma. It is increasingly important yet challenging to remain up-to-date on the arsenal of treatments available for melasma to find an efficacious and well-tolerated option for our patients.

Nanosystems with potential application as carriers for skin depigmenting actives.

Hyperpigmentation is a skin disorder characterized by excessive production of melanin in the skin and includes dyschromias such as post-inflammatory hyperchromias, lentigens, melasma and chloasma. Topical products containing depigmenting agents offer a less aggressive treatment option for hyperpigmentation compared to methods like chemical peels and laser sessions. However, some of these agents can cause side effects such as redness and skin irritation. Encapsulating these actives in nanosystems shows promise in mitigating these effects and improving product safety and efficacy. In addition, nanocarriers have the ability to penetrate the skin, potentially allowing for targeted delivery of actives to the affected areas. The most commonly investigated nanosystems are nanoemulsions, vesicular nanosystems and nanoparticles, in which different materials can be used to generate different compositions in order to improve the properties of these nanocarriers. Nanocarriers have already been widely explored, but it is necessary to understand the evolution of these technologies when applied to the treatment of skin hyperchromias. Therefore, this literature review aims to present the state of the art over the last 15 years on the use of nanosystems as a potential strategy for encapsulating depigmenting actives for potential application in cosmetic products for skin hyperchromia. By providing a comprehensive overview of the latest research findings and technological advances, this article can contribute to improving the care and quality of life of people affected by this skin condition.

Worldwide internet trends in the public interest related to skin whitening and bleaching creams.

Skin whitening is a practice that is used to obtain lighter skin tone and is most prevalent in Africa and Asia. Substances used for this procedure, such as hydroquinone or mercury have a variety of side effects and are banned in several countries. This study examined the popularity of internet searches for terms related to skin whitening and bleaching creams with the use of GoogleTrends (GT). GT was searched globally for the topic "skin whitening" and two terms "hydroquinone cream" and "mercury cream" throughout a 10-year period (01.09.2013-31.08.2023). The popularity of searches increased during the analyzed period. The topic "skin whitening" was most popular in Sudan, Vietnam, and Sri Lanka. The searches were higher for "hydroquinone cream" than "mercury cream" in almost all countries, besides the Philippines and Indonesia. Our study confirms that skin whitening practices are popular, especially among populations with darker skin tone. Despite potentially toxic side effects, creams with hydroquinone and mercury are increasingly searched worldwide. Education about skin whitening and the usage of bleaching substances should be implemented, especially in the regions of Africa and Asia.

Establishment of an in vitro cell coculture model for investigating the whitening mechanism of Paeonia lactiflora Pall seeds oil.

BACKGROUND: In vitro single-cell experiments may yield inconsistent results compared to clinical trials. To enhance the reliability of cosmetic active ingredient screening, a coculture model of B16F10-HaCaT cells was established in vitro based on the structural characteristics of human skin, thereby improving the credibility of experimental outcomes. Currently, most cosmetic whitening additives primarily target simple efficacy goals such as inhibiting tyrosinase activity or melanin transfer. Therefore, investigating novel and efficient whitening additives has become a prominent research focus. OBJECTIVES: The aim is to establish an in vitro cell coculture model for more reliable experimental results and investigate the mechanism by which Paeonia lactiflora Pall seeds oil inhibits melanin production and transfer. METHODS: The impact of different concentrations of Paeonia lactiflora Pall seeds oil on cocultured cell proliferation rate was assessed using cck8 assay. Tyrosinase inhibition ability in cocultured cells was tested using levodopa as a substrate. Melanin production inhibition ability in coculture cells was evaluated by lysing cells with sodium hydroxide. The effect of Paeonia lactiflora Pall seeds oil on dendrite-related gene expression levels was examined through qPCR analysis. Additionally, Western blotting was employed to study the effect of Paeonia lactiflora Pall seeds oil on dendrite-related protein expression levels. RESULTS: Different concentrations of Paeonia lactiflora Pall seeds oil did not affect the proliferation activity of cocultured cells. A specific concentration of α-MSH increased cell tyrosinase activity, cellular melanin content, as well as Rac1, Cdc42, and PAR-2 gene and protein expression related to dendritic formation. Treatment with a certain concentration of Paeonia lactiflora Pall seeds oil resulted in decreased tyrosinase activity and melanin content in cells along with downregulated expression levels of Rac1, Cdc42, and PAR-2 genes and proteins associated with dendritic formation. CONCLUSIONS: Paeonia lactiflora Pall seeds oil at specific concentrations exhibits the ability to inhibit tyrosinase activity, decrease melanin content, and possesses the potential to impede melanin transfer.

Components analysis of San-Bai decoction, and its pharmacodynamics and mechanism on preventing and treating melasma.

ETHNOPHARMACOLOGICAL RELEVANCE: San-Bai Decoction (SBD) is a classic whitening prescription originally recorded in the 'Introduction to Medicine' of the Ming Dynasty. SBD has been known for invigorating Qi and blood, promoting spleen and stomach, whitening skin, and fading melasma. However, its pharmacodynamic material basis and specific mechanism remain unclear. AIM OF THE STUDY: The aim of this study is to clarify the pharmacodynamic material basis of SBD and its mechanism of removing melasma. MATERIALS AND METHODS: The positive and negative ion mass spectrum data of SBD extract were collected by UHPLC-Q-Exactive Orbitrap MS/MS, imported into Compound Discoverer (CD) 3.1 software, matched through the online database, and manually checked. Finally, the in vitro chemical components of SBD were classified. Similarly, the mass spectrum data of SBD in the serum of normal rats and melasma model rats were also analyzed by CD 3.1 software. The in vitro identified Compound file of SBD was imported into the Expected Compounds and the Generate Expected Compounds project was selected. The SBD compounds were then chosen under the Compound Section. All phase I and II reaction types related to SBD components were selected, and the metabolic platform of CD 3.1 software was utilized to process the results and obtain possible metabolites. The metabolites were scored and products with high scores were subsequently screened. According to literature comparison, the final metabolites of SBD in both normal rats and melasma model rats were determined and comprehensively analyzed. The Melasma model rats were constructed through intramuscular injection of progesterone and ultraviolet radiation B (UVB) irradiation. The preventing and treating effect of SBD on melasma were evaluated by regulating inflammation, epidermal collagen content, and oxidative stress. Additionally, the effect of SBD on the Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt)/Glycogen synthase kinase 3ß (GSK3ß) pathway was investigated through Western blot (WB) to explore its underlying mechanism on whitening and removing melasma efficacy. RESULTS: Ultimately, 94 components were identified in SBD, including 41 flavonoids, 27 organic acids, and 9 glycosides, 3 terpenoids, 2 amides, 2 aldehydes, 1 phenylpropanoid and 9 other compounds. In the blood of normal rat group, a total of 24 prototype components and 61 metabolites were identified. Similarly, there were19 prototype components and 44 metabolites identified from the blood of melasma model rats. Pharmacodynamic experiment results indicated that SBD effectively reduced the incidence of melasma, prevent the loss of epidermal collagen, and elevate the activity of superoxide dismutase and decrease the malondialdehyde content in both liver and skin. Interestingly, the WB results demonstrated that SBD effectively activated PI3K/Akt/GSK3ß pathway, and down-regulated the expression of melanin-related proteins. CONCLUSIONS: For the first time, the components of SBD extracts, and its prototype components and metabolites in the blood of normal rats and melasma model rats were successfully identified by high-resolution liquid chromatography-mass spectrometry with CD software. Additionally, the differences of in vivo components of SBD between normal rats and melasma model rats were analyzed. The preventive and therapeutic effect of SBD on melasma was verified in the melasma model rats induced by progesterone and UVB irradiation, and its mechanism was related to activating PI3K/Akt/GSK3ß pathway and downregulating the expression of melanin-related proteins. These results provide an experimental foundation for further research on the pharmacodynamic substance basis and pharmacodynamic mechanism of SBD, as well as developing new anti-melasma formula with SBD.

Quantification of Arbutin and its degradation products, hydroquinone and p-Benzoquinone, in hyperpigmentation topical formulation: Effect of extraction procedure and interference assessment.

The utilization of Hydroquinone (HQ) in over-the-counter skincare items is subject to restrictions. Consequently, Arbutin (AR) serves as a reliable alternative for addressing hyperpigmentation in non-prescription topical formulations. Nevertheless, AR undergoes decomposition into HQ and p-Benzoquinone (BZ) when exposed to temperature stress, ultraviolet light, or dilution in an acidic environment, all of which can induce skin toxicity. The intention of this paper is to investigate the effect of extraction procedure on the conversion of AR to HQ and or BZ and to evaluate kinetics of AR hydrolysis to HQ. Meanwhile this study aims to evaluate AR and BZ interference with the United States Pharmacopoeia (USP) identification and assessment method for HQ Hydrolytic stress during extraction conditions underwent optimization through systematic screening tests. Subsequent assessment of the residual drug and its degradation products were achieved by HPLC method. The resulting data were meticulously fitted to various kinetic models. To analyze the potential interference of AR in HQ measurement using USP method, the standard concentrations of AR and HQ were analyzed through UV-VIS spectrophotometry. For enhanced certainty, a validated HPLC method analysis was also conducted. Notably, the acid hydrolysis of AR exhibited independence from its initial concentration. So, the hydrolytic degradation of AR exhibited a Zero-order kinetic profile. Furthermore, the proven interference of AR in the UV-VIS spectrophotometry method was identified within the context of the USP method. This study successfully utilized an adopted HPLC method for the concurrent quantification of AR, HQ, and BZ. The potential interference of AR in the UV-VIS spectrophotometric assay for HQ may lead to false results especially for regulatory purposes.

Cosmetic skin lightening: Contextualizing biomedical and ethical issues.

The skin-lightening (SL) industry has a global reach and is projected to continue to grow over the coming decade. Although SL treatments may be safely prescribed for the treatment of some dermatologic conditions, many over-the-counter SL products contain ingredients that can cause harm to the skin and other organ systems. Given a lack of transparent information to patients and the historical colorist foundation that contextualizes a component of the cosmetic SL industry, dermatologists need to navigate biomedical and ethical concerns when explaining SL products to patients. This commentary briefly outlines the medical ethical issues surrounding this topic and describes avenues by which dermatologists may provide informed patient care that best supports beneficence, justice, autonomy, and nonmaleficence.

The whitening efficacy of a compound formula examined using an ultraviolet-induced skin melanization model.

BACKGROUND: In Eastern culture, a fair complexion is the standard of beauty, leading to appearance-related distress among women with darker skin or facial pigmentation. Women seek whitening cosmetics to enhance their skin tone or correct their pigmentation, but their safety and effectiveness are paramount factors to consider. In this study, we evaluated the safety and whitening effects of a compound formula denoted as TEST comprising astaxanthin, nicotinamide, arbutin, and tranexamic acid. METHODS: Primary skin irritation and skin-whitening efficacy were examined. Three qualified melanization areas were treated with TEST, 7% ascorbic acid, or a blank. Skin color, the individual type angle (ITA°), and the melanin index (MI) were compared among treatment areas. RESULTS: TEST did not induce a skin response and exhibited a significantly higher ITA° than the blank, while no significant difference was observed with that of 7% ascorbic acid. Furthermore, the MI of TEST was significantly reduced posttreatment. CONCLUSIONS: TEST could be integrated into spot-fading and skin-whitening cosmeceuticals or functional cosmetics.

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).