ALPHA-ARBUTIN

The combined therapy of alpha arbutin, a natural derivative of hydroquinone, and niacinamide is well-regarded in skincare science. It leverages the unique properties of both actives, providing a multifaceted solution to esthetic and therapeutic skin concerns and supporting a comprehensive approach to skincare. This study aimed to develop a robust HPTLC method to determine alpha arbutin and niacinamide in a nanocosmeceutical using a comprehensive approach that includes risk assessment and Analytical Quality by Design. The critical method parameters influencing the HPTLC results were screened using a Plackett-Burman screening design, followed by optimization using a central composite optimization design and validation of the optimized method as per ICHQ2(R2). A novel HPTLC utilized pre-coated aluminum-backed HPTLC plates of Silica gel G 60 F 254 using 10 µL/band injection volume, and the plate was developed using an isocratic mobile phase consisting of ethyl acetate: methanol: water (8.4:0.8:0.8v/v/v) in a twin trough chamber pre-saturated for 30 mins with vapors of 10 mL of mobile phase. The separated components were detected at a wavelength of 273 nm. The developed HPTLC method resulted in a retardation factor of 0.31 ± 0.02 for alpha arbutin and 0.42 ± 0.02 for niacinamide, respectively. Validation results revealed the HPTLC method's specificity (peak purity ≥ 0.999), linearity (over a studied concentration range of 200-800 ng/band for alpha arbutin and 400-1600 ng/band for niacinamide), sensitivity, accuracy, precision, and robustness. The developed robust HPTLC method was successfully implemented for the sustainable testing of the alpha arbutin and niacinamide in the nanocosmeceutical formulations.

Photoaging is induced by prolonged UVB exposure, leading to the production of reactive oxygen species and subsequent oxidative stress. Cinnamomum burmanni essential oil (CBEO) is known for its potent antioxidant properties. This study aimed to develop a CBEO nanoemulgel formulation that provides optimal anti-photoaging effects will be proven by in vivo and in silico evaluation. Additionally, molecular docking studies were conducted to explore the interaction between the bioactive compounds and Matrix Metalloproteinase-2 (MMP-2), a key enzyme involved in the degradation of collagen during photoaging, to support the proposed mechanism of action. CBEO was found to contain 88.59% cinnamaldehyde as its main compound. Skin histopathological analysis demonstrated anti-photoaging effects of CBEO nanoemulgel were comparable to alpha arbutin both in vivo and in silico . The developed CBEO nanoemulgel demonstrates strong potential as a topical anti-photoaging agent, attributed to its rich content of bioactive compounds with MMP-inhibitory properties.

Chitosan is a cationic polysaccharide derived from chitin with film-forming, bioadhesive, antimicrobial, and wound-modulating properties, supporting increasing interest in aesthetic dermatology. To synthesize clinically relevant evidence on chitosan and its derivatives in aesthetic practice, focusing on skin barrier support, post-procedure recovery, acne, pigmentary disorders, and scalp applications. A narrative review of PubMed/Medline literature through February 2026 was conducted, prioritizing clinical trials, split-face studies, and relevant human data, supported by mechanistic and formulation evidence. Clinical studies suggest that chitosan hydrogels can support post-procedural recovery after ablative laser treatments with outcomes comparable to standard regimens and improved tolerability. Chitosan-based delivery systems enhance topical performance of actives such as nicotinamide, spironolactone, and α-arbutin in acne and melasma. In scalp applications, microneedling-assisted topical chitosan demonstrated improvements in hair density comparable to minoxidil in small studies. Chitosan shows potential as a barrier-supportive material, a delivery platform for topical actives, and an adjunct in scalp therapies. However, heterogeneity in formulations and limited study sizes restrict generalizability. Larger, standardized clinical trials are needed to define its role in aesthetic protocols.

α-Arbutin and its derivatives are widely recognized for their potent antioxidant activity and clinically validated skin-lightening effects. However, conventional synthetic strategies often rely on multistep protection-deprotection procedures, which reduce overall efficiency and limit scalability. The objective of this study was to develop a simple, one-step, and stereo- selective method for synthesizing α-Arbutin and related sugar derivatives using a heterogeneous solid acid catalyst under mild and sustainable reaction conditions. An ultrasonic-assisted glycosylation protocol was developed using Fe/SiO₂ as a reusable solid acid catalyst. Reactions were performed with unprotected sugars in various solvents at 35-40 °C. Ultrasonic irradiation was employed to enhance reaction kinetics and mass-transfer efficiency. Reaction progress, stereoselectivity, and product purity were monitored using TLC, NMR, and HPLC analyses. Catalyst recyclability and structural stability were evaluated across several reaction cycles. The protocol successfully produced α-Arbutin and multiple sugar derivatives in good to excellent yields (3a-3f). Ultrasonication significantly shortened reaction time while maintaining high product purity and selectivity. The Fe/SiO₂ catalyst exhibited strong acidity, high catalytic performance, and excellent reusability. Unprotected sugars afforded the desired α-anomer with remarkable stereoselectivity across different solvents. The method avoided protection- deprotection steps and generated minimal by-products, demonstrating operational simplicity and efficiency. These findings highlight that coupling ultrasonic energy with a heterogeneous solid acid catalyst provides a greener, faster, and more selective glycosylation strategy that aligns with sustainable synthesis principles. The ultrasonic-assisted Fe/SiO₂-catalyzed one-step synthesis offers an efficient, environmentally compatible, and stereoselective route for producing α-Arbutin and its derivatives (3a- 3f), supporting their potential application in cosmetic and pharmaceutical formulations.

α-Arbutin is a skin-lightning agent that has been widely used in cosmetic and pharmaceutical formulations to treat hyperpigmentation disorders such as melasma and solar lentigo. It has fewer reported adverse effects in humans than hydroquinone and greater efficacy than β-Arbutin. However, few studies have focused on evaluating its toxicity profile, particularly its genetic toxicity. The aims of this study were to evaluate the cytotoxic, genotoxic, and mutagenic effects of α-Arbutin following a preliminary in silico analysis of toxicity-related parameters. Cytotoxicity and genotoxicity were assessed using the MTT and comet assays, respectively, whereas mutagenic activity was examined with the cytokinesis-block micronucleus cytome assay (CBMN-Cyt) and the Salmonella/microsome assay (Ames test). In the MTT assay, α-Arbutin exhibited an IC 50 (24 h) of 43.5 ± 0.02 μM and displayed genotoxic activity in L929 fibroblast cells treated for 3 h, regardless of a 21 h recovery period. Despite the observed genotoxic effects in the comet assay, no mutagenic activity was detected in either the Ames test or the CBMN-Cyt assay, in agreement with the in silico analysis, indicating that α-Arbutin did not induce gene or chromosomal mutations under the tested conditions.

The primary objective of this study was to investigate the biological activities of freeze-dried Ganoderma lucidum (Reishi) extract obtained from hazelnut pruning waste and to compare its antioxidant, tyrosinase inhibitory and cytotoxic properties with two widely used cosmetic actives-argireline peptide and α-arbutin. Additionally, the study aimed to develop a topical cream formulation containing Reishi extract and to assess its microbiological safety, preservative efficacy and physicochemical stability under controlled environmental conditions. By integrating bioactivity evaluation with formulation performance, the research sought to determine the potential applicability of Reishi extract as a natural and multifunctional cosmetic ingredient suitable for anti-aging and skin-brightening applications. The antioxidant capacity of Reishi extract, argireline peptide and α-arbutin was determined using a copper(II)-based total antioxidant capacity assay. Tyrosinase inhibitory activity was measured with human tyrosinase sourced from MNT-1 melanoma cells, while cytotoxicity and safe dose limits were determined in HaCaT human keratinocyte cells via the AlamarBlue® method. A topical cream formulation was prepared using a multi-phase emulsification technique and characterized physicochemically. Microbiological safety was assessed according to Turkish Cosmetic Regulations, and preservative efficacy was determined through challenge testing. Stability assessments included temperature cycling, long-term storage at different temperatures and centrifugation tests, monitoring visual, physicochemical and microbiological parameters over a three-month period. Reishi extract demonstrated 861 μmol TE/g antioxidant activity, 30% tyrosinase inhibition and a broader safety margin compared with argireline peptide and α-arbutin, which exhibited cytotoxicity at lower concentrations. The formulated cream retained a skin-compatible pH and stable viscosity, while showing no signs of phase separation, colour change or integrity loss under all storage conditions. Microbiological analysis confirmed microbial counts below regulatory limits, and challenge testing revealed rapid log reductions in all tested microorganisms, satisfying the acceptance criteria for preservative efficacy. Stability studies supported the physical robustness and microbiological safety of the final product throughout the evaluation period. Overall, the findings highlight Reishi extract as a bioactive-rich, safe and stable natural ingredient with strong potential for incorporation into cosmetic formulations. Its antioxidant performance, moderate tyrosinase inhibition and compatibility within the cream matrix support its use in multifunctional anti-aging and skin-brightening products. L'objectif principal de cette étude était d'étudier les activités biologiques de l'extrait de Ganoderma lucidum lyophilisé (Reishi) obtenu à partir des déchets d'élagage des noisettes et de comparer ses propriétés antioxydantes, inhibitrices de la tyrosinase et cytotoxiques avec deux actifs cosmétiques largement utilisés : un peptide d'argireline et d'α‐arbutine. Par ailleurs, l'étude visait à développer une formulation de crème topique contenant de l'extrait de Reishi et à évaluer sa sécurité microbiologique, son efficacité de conservation et sa stabilité physicochimique dans des conditions environnementales contrôlées. En intégrant l'évaluation de la bioactivité à la performance de la formulation, la recherche a cherché à déterminer l'applicabilité potentielle de l'extrait de Reishi en tant qu'ingrédient cosmétique naturel et multifonctionnel adapté aux applications anti‐âge et d'éclaircissement de la peau. MÉTHODES: La capacité antioxydante de l'extrait d

Phytochemical investigation of Butea monosperma (Lam.) Kuntze flowers resulted in the isolation of seven compounds: medicarpin ( 1 ), sulfuretin ( 2 ), liquiritigenin ( 3 ), kaempferol ( 4 ), butein ( 5 ), iso-butrin ( 6 ), and butrin ( 7 ). Structures were identified by 1D and 2D NMR and confirmed with literature data. Antioxidant assays (DPPH • , ABTS •+ , FRAP) revealed butein ( 5 ) as the most active, followed by sulfuretin ( 2 ) and iso-butrin ( 6 ). Liquiritigenin ( 3 ) exhibited the strongest tyrosinase inhibition (IC 50 = 13.07 ± 2.58 µM) via competitive inhibition and effectively suppressed melanin production in MNT-1 cells, reducing pigmentation by 22-41%, outperforming α-arbutin without cytotoxicity. Compounds 4 and 5 showed potent anti-inflammatory activity, with NO inhibitory IC 50 values of 51.60 and 66.93 µM, respectively, while 2 , 3 , 5 , and 6 exhibited moderate cytotoxicity against HeLa (IC 50 = 34-38 µM) and HCT116 cells (IC 50 = 21-28 µM). Overall, B. monosperma flowers provide multifunctional natural products with promising cosmetic and pharmaceutical potential.

Melasma and other hyperpigmentation disorders represent a significant challenge in dermatology. Tranexamic acid (TXA), traditionally known for its antifibrinolytic activity via inhibition of plasminogen activation, has recently emerged as a promising depigmenting agent. However, its cellular effects on skin cells involved in melanogenesis remain poorly understood. In this study, we investigated TXA's impact on melanocytes, keratinocytes, and inflammatory cells. TXA directly inhibited melanin synthesis in B16 melanoma cells, with an additive effect when combined with α-arbutin. In keratinocytes and macrophages, TXA attenuated inflammatory responses triggered by the plasminogen/plasmin (Plg/Plm) pathway. Moreover, TXA reduced lipopolysaccharide-induced pro-inflammatory gene expression in mouse macrophages, suggesting interference with Toll-like receptor-mediated inflammation. These findings highlight TXA's multifaceted actions on skin cells involved in pigmentation and support its therapeutic potential in melasma and potentially other skin diseases.

This study aimed to address the limitations of α-arbutin (α-Arb) in transdermal delivery and melanin inhibition by developing a tetrahedral framework nucleic acid (tFNA)-based nanocarrier (tFNA@α-Arb). Unlike conventional carriers, tFNA was chosen for its unique tetrahedral structure and nucleic-acid-derived biocompatibility, which enables superior skin penetration. A first-reported thermal loading method for nucleic acids was applied to encapsulate α-Arb, significantly enhancing the loading efficiency from 60.83% to 76.85% without compromising drug activity. Subsequent transdermal experiments demonstrated that tFNA could deposit in the epidermis and accumulate within the skin. Zebrafish experiments further validated the excellent transdermal properties and safety profile of tFNA@α-Arb, which resulted in an effective melanin reduction with an inhibition rate of 95.65%. Mechanistically, tFNA@α-Arb specifically downregulated melanin-synthesis-related genes (validated by RT-qPCR). In C57BL/6J mice, it showed more pronounced melanin reduction, confirming the synergistic effect of tFNA's delivery capability and α-Arb's activity. This study presents a tFNA-based platform that innovates both carrier design and loading strategy, offering a transformative solution for enhancing α-Arb's efficacy in melanin inhibition.

α-Arbutin, a glucoside of hydroquinone, is utilized as a skin-lightening agent that inhibits human tyrosinase activity. Although it exhibits antioxidant and anti-inflammatory properties, limited research exists on its toxicological effects. This research investigates the oral toxicity of α-arbutin in both acute and subacute settings using Sprague-Dawley rats as test subjects. Female Sprague-Dawley rats underwent acute oral toxicity testing in accordance with OECD TG 425 guidelines. The rats received oral doses of 175, 550, 1750, and 2000 mg/kg. Additionally, a subacute oral toxicity study following OECD TG 407 protocols was performed on both male and female rats. In this study, the animals were given daily oral doses of 250, 500, 1000, and 2000 mg/kg for 28 days. During acute and subacute oral toxicity assessments, no deaths or observable changes in behavior were noted at the administered doses. Examination of gross anatomy showed a significant decrease in the relative spleen weight of rats given α-arbutin at 250 mg/kg compared to the control group. Male rats treated with α-arbutin exhibited markedly non-significantly increased levels of AST, ALT, and chloride ions. In contrast, mean corpuscular hemoglobin concentration levels notably decreased at lower α-arbutin doses relative to the control group. Brain histopathology of male rats revealed moderate inflammation with pyknotic nuclei, whereas the cortex showed extensive epithelial cell necrosis following the administration of 2000 mg/kg of α-arbutin. The results showed that when given for a short time, α-arbutin is nontoxic till 2000 mg/kg. The median lethal dose (LD 50 ) of α-arbutin is more than 2000 mg/kg. A long-term toxicity study may be performed to validate the result. This study evaluated the acute and subacute oral toxicity of α-arbutin in Sprague-Dawley rats. No mortality or significant behavioral changes were observed up to 2000 mg/kg. However, at higher doses, male rats exhibited elevated liver enzymes and chloride ions, along with brain inflammation and cortical necrosis. Overall, α-arbutin showed no remarkable toxicity at tested doses, with an LD 50 exceeding 2000 mg/kg, warranting further long-term safety assessments.

Skin hyperpigmentation is a dermatological concern for pigmented skin phototypes. Despite availability of multiple treatment options, hyperpigmentation management continues to be a challenge. Efficacy and safety assessment of the skincare regimen [topical formulation of trihydroxybenzoic acid glucoside 10% (THBG) and α-arbutin 2% (twice-daily) + sunscreen (once daily)] in Indian females with pigmentary spots (facial dark spots or melasma). This prospective, open-label, single-arm, interventional study was conducted in Indian females (n = 124), aged 18-45 years, having FitzPatrick skin type III-IV, dull skin, and facial dark spots or melasma. Efficacy of 90-day skincare regimen was evaluated using mexameter, modified melasma area and severity index (mMASI) score, cross-polarized light photography, chromameter, and color-luminosity-brightness-transparency (CLBT) technique. Student's t-test (paired data) was used for statistical analysis. In efficacy analysis [modified intention-to-treat (mITT) population], 120 subjects were included. Melanin content of pigmentary spots (on mexametry) significantly reduced (-16.3%, p < 0.001) at Day 90 versus baseline. Significant reduction in severity of melasma was observed (-18.4% in mMASI score) at Day 90. Significant improvement in ΔEab (-8.7%) (change in color difference between pigmentary spot and normal skin) on cross-polarized photographs, in skin-brightening parameters L* (relative brightness/lightness) (-2.7%), ITA° (individual typology angle) (-37.7%), and ΔE* (skin-tone evenness) (-19.0%) using chromameter. Significant improvement in skin radiance was observed in CLBT parameters, color (pink: 32.8%, yellow: -5.5%, and olive: -7.8%), luminosity (6.0%), brightness (4.6%), and transparency (0.2%). Regimen did not cause itching, burning, or irritation. Skincare regime of 10% THBG and 2% α-arbutin along with sunscreen was effective in reducing pigmentary spots (dark spots and melasma) and was well tolerated in Indian women. Clinical Trial Registry of India (CTRI Reg. No. CTRI/2021/11/038345; date: 30/11/2021).

Natural products and botanicals continue to play a very important role in the development of cosmetics worldwide. The chemical constituents of a fine active fraction of the whole plant extract of Cuphea hookeriana Walp., and the tyrosinase and matrix metalloproteinase-1 (MMP-1) inhibitory and antioxidant activities of this fraction were investigated. The fine active fraction was mainly composed of seven natural compounds. The fine active fraction demonstrated substantial in vitro antioxidant potential using the ABTS assay (IC 50 1.66 μg/mL). It inhibited the two target enzymes (tyrosinase and MMP-1) engaged in skin whitening and aging with comparable IC 50 values to the reference drugs. Acute toxicity experiments showed that mice gavage orally with the fine active fraction had no significant animal toxicity at a dose of 2000 mg/kg, and the maximum tolerated dose (MTD) in mice was greater than 2000 mg/kg. In a model where ultraviolet light promotes the increase in melanin secretion in guinea pig skin tissues, both α-arbutin and the fine active fraction can reduce melanogenesis, and the effect of the fine active fraction is better than that of α-arbutin.