ABSTRACT The edible fungus Aspergillus oryzae is well known for its powerful ability to secrete numerous proteolytic enzymes, such as lipases, proteases, and amylases. However, the mechanisms that regulate the translation of these enzymes in A. oryzae remain poorly understood. In this study, we investigated the biological function of the translation initiation factor eIF3j in A. oryzae. Our findings revealed that deletion of the eIF3j gene significantly inhibited mycelial growth and conidiation compared with the control strain. Furthermore, the eIF3j mutant showed increased sensitivity to various stressors relative to the control strain. Interestingly, the eIF3j-deleted strain exhibited enhanced production of amylase and kojic acid when compared with the control strain. Additional quantitative proteomic analysis suggested that eIF3j was involved in RNA processing, ribosome biogenesis, and amino acid metabolism. Taken together, these findings underscore the multifaceted role of eIF3j in A. oryzae and its potential as a target for improving traits relevant to industrial applications.

Compounds containing an azomethine functional group are well recognized for their enzyme inhibitory potential. In this study, a series of hydrazone-Schiff base derivatives from 4-(tert-butyl)benzoic acid was synthesized and evaluated for their inhibitory activity against α-amylase, α-glucosidase, and tyrosinase. assays demonstrated pronounced multi-target inhibition. Against α-amylase, compound 2l, bearing a para-nitro substituent, exhibited strong activity with an IC50 of 2.72 ± 0.09 µM, significantly outperforming the reference acarbose (IC50 = 16.06 ± 0.05 µM; p < 0.001). Similarly, compound 2l showed potent α-glucosidase inhibition (IC50 of 3.96 ± 0.21 µM), which was markedly superior to acarbose (IC50 = 16.65 ± 0.07 µM; p < 0.001). In the tyrosinase inhibition assay, the dimethoxy-substituted derivative 2r emerged as the most active compound, with an IC50 of 5.61 ± 0.03 µM, approximately threefold more potent than kojic acid (IC50 = 15.29 ± 1.04 µM; p < 0.001). Molecular docking studies against α-amylase, α-glucosidase, and tyrosinase (PDB IDs: 3BAJ, 5NN5, and 5M8Q, respectively) revealed favorable binding energies ranging from −5.2 to −5.8 kcal/mol and highlighted key interactions with catalytic residues. Density functional theory (DFT) and molecular electrostatic potential (MEP) analyses provided an electronic basis for the observed structure-activity relationships, indicating that enhanced electrophilicity favors glycosidase inhibition, whereas increased nucleophilicity contributes to tyrosinase inhibition. Overall, these findings identify hydrazone Schiff base derivatives as promising scaffolds for the development of multifunctional enzyme inhibitors, with compounds 2l and 2r representing potential lead candidates for further optimization.

Determination of dissociation constants between single-protein and multicomponents by a multi-chamber membrane separation electrophoresis system as a complementary tool.

Kojic acid inhibits melanoma progression by targeting the MYC-CCNA2/KPNA2 axis.

A series of isatin-based Schiff base derivatives (1-12) was synthesized via a two-step reaction and characterized using spectroscopic techniques such as 1H-NMR and mass spectrometry. The urease and tyrosinase inhibitory activities of the synthesized compounds were evaluated using thiourea (IC50 = 21.25 ± 0.15µM) and kojic acid (IC50 = 121 ± 0.5µM) as standard inhibitors. Among the synthesized analogs, only three compounds-1 (IC50 = 38.9 ± 0.06µM), 3 (IC50 = 56.7 ± 0.02µM), and 10 (IC50 = 71 ± 0.09µM) showed moderate urease inhibition, while the remaining compounds were inactive. All compounds were inactive against tyrosinase inhibition. The structure-activity relationship (SAR) of the active analogs was established based on the nature, position, and number of substituents on the phenyl ring of the basic nucleus of the compounds. Molecular docking studies were performed to confirm the binding interactions of the most potent analogs with the active site of urease. The docking results revealed that compound 1 formed six strong intermolecular interactions with the binding site residues of urease, exhibiting the lowest docking score of -4.8944. The findings suggest that the synthesized isatin-based Schiff base derivatives, particularly compounds 1, 3, and 10, could serve as potential lead compounds for developing novel urease inhibitors.

A novel tyrosinase immobilization strategy based on hydrophilic multivariate mesoporous metal-organic frameworks for ligand fishing of tyrosinase inhibitors from herbal medicines.

Background : Ultraviolet rays and pollution cause premature aging of the skin, darkening, dryness, and decreased elasticity. Parijoto fruit (Medinilla speciosa) offers potential for development as an anti-aging agent. Methods : The current research was conducted to investigate the influence of Extended Pharmaceutical Marketing Mix (product, price, place, promotion, pharmacist, process and physical evidence) on customer satisfaction at pharmacies in Jember. . Four fractions were obtained through liquid-liquid partition using n-hexane, ethyl acetate, butanol, and water solvents. Elastase and tyrosinase enzyme inhibition tests were carried out in vitro using an ELISA (multi-mode reader). The reference compound in the elastase enzyme inhibition test was gallic acid, and kojic acid was used to inhibit the tyrosinase enzyme. Results: The elastase enzyme inhibitory activity of the extract and four fractions and gallic acid with a concentration of 133.33 μg/mL were 13.28; 21.56; 14.88; 15.12; 11.24; and 21.83%. The tyrosinase inhibitory activity of parijoto fruit extract and four fractions and kojic acid with a concentration of 125 μg/mL were 17.01; 19.2; 23.96; 14.76; 18.20; 34.71%, respectively. Parijoto fruit extract and fractions had elastase and tyrosinase inhibitory activity. Conclusions: The n-hexane fraction was the active fraction in inhibiting the elastase enzyme by 21.56%, while the active fraction in inhibiting the tyrosinase enzyme was the ethyl acetate fraction which provided an activity of 23.96%.

Staphylococcus aureus is a major skin pathogen that causes a broad spectrum of infections, ranging from mild skin infections to severe invasive diseases. In this study, we evaluated antibacterial and antivirulence properties of selected FDA-approved skincare bioactives and antiseptics against multiple virulence factors. Minimum inhibitory concentration analysis of benzalkonium chloride, retinol, hydroquinone, and kojic acid showed strong antimicrobial activity at concentrations from 2 to 1024µg/mL. Epigallocatechin gallate effectively inhibits biofilm formation by 81.53% and reduces staphyloxanthin production by 68.26%. Retinol exhibited antibiofilm activity, eradicating mature biofilm mass by 79.18%. Furthermore, a combination of skincare bioactives with antibiotics, including oxacillin, ciprofloxacin, tetracycline, and rifampicin, demonstrated synergy and additive effects, enhancing antibacterial efficacy. Molecular docking analysis exhibited strong predicted binding affinities of skincare bioactives and antiseptics against key virulence factors. This study highlights the multitarget antivirulence potential of skincare bioactives and antiseptics as an alternative strategy to mitigate diverse S. aureus infections.

Ecofriendly and sustainable antifouling (AF) compounds are required to replace toxic additives in maritime AF coatings. Our group has developed synthetic AF compounds with anti-settlement activity toward Mytilus galloprovincialis mussel with nontoxic properties against this target organism. Some compounds have shown to be capable of modulating the activity of key enzymes involved in mussel settlement, namely, tyrosinase and acetylcholinesterase (AChE). The saturation transfer difference nuclear magnetic resonance (STD-NMR) technique is a powerful ligand-based approach to disclose the moieties responsible for binding to macromolecules in solution. This work aimed to study the binding mode of two AF compounds, a xanthone and a polyphenol, with tyrosinase and AChE, respectively, by using STD-NMR. The obtained results showed that the tyrosinase inhibitor exhibited an epitope map based on the hydroxylated aromatic ring, whereas theAChE inhibitor established interactions with both the aromatic ring and the aliphatic moiety. Further competition assays with established inhibitors, namely, kojic acid for tyrosinase and eserine for AChE, suggested that the xanthone derivative engages tyrosinase in a competitive manner, whereas the polyphenol interacts with AChE at sites distinct from the catalytic active site. These structural insights will help the rational design for optimized AF agents by targeting tyrosinase and AChE.

Hyperpigmentation disorders stem from tyrosinase-catalyzed melanin overproduction, worsened by ultraviolet oxidative stress. The native Chilean species Cryptocarya alba, Laurelia sempervirens, and Peumus boldus are sources of aporphine and benzylisoquinoline alkaloids, known for their antioxidant activity. Boldine derivatives, notably diacetylboldine (DAB, Lumiskin™), demonstrate commercial depigmenting efficacy, yet structure-activity relationship data are limited.​. Systematically evaluate pure alkaloids and boldine derivatives for tyrosinase inhibition via mushroom enzyme assays, molecular docking, human melanocyte (HEMn-DP), and 3D epidermal (MelanoDerm™) models to elucidate depigmenting mechanisms. Boldine (BOL), N-methyllaurotetanine (NMLT), laurolitsine (LTS), laurotetanine (LTT), and reticuline (RET) alkaloids were isolated from authenticated plant material via acid-base partitioning/silica gel chromatography; structures were confirmed by 1H-NMR/UHPLC-MS/MS (98% HPLC purity). Coclaurine (CC), N-methylcoclaurine (NMCC), and BOL derivatives: 3-bromoboldine (3BrBOL) and DAB were synthesized. Isocorydine (ISO) was obtained commercially. Mushroom tyrosinase (EC 1.14.18.1) inhibition measured spectrophotometrically (475nm, L-DOPA; IC50 interpolation). Docking performed on A. bisporus tyrosinase (PDB:2Y9X) with AutoDock Vina (30 × 30 × 30Å grid). HEMn-DP cells treated (40/250ppm, 24h) for MTS viability and alkali-solubilized melanin (450nm). MelanoDerm™ tissues were dosed topically (0.1% w/v) for 14 days, followed by the Solvable™ melanin assay (490nm). Data analyzed in GraphPad Prism 8 (Dunnett's test, P < 0.05). LTS (IC50 = 0.96mM), an aporphine alkaloid, followed by CC (1.29mM), a benzylisoquinoline alkaloid, were the most potent mushroom tyrosinase inhibitors, outperforming BOL 6.8- and 5.1-fold (6.56mM), respectively, yet trailing reference standards such as kojic acid (0.014mM). Boldine derivatives, including DAB (2.22mM) and 3BrBOL (1.96mM), exhibited superior potency relative to the parent compound. Docking revealed LTS's highest affinity (-7.3kcal/mol; H-bonds: His259 3.4Å, Asn260 3.2Å) versus BOL (-5.3kcal/mol; solely van der Waals), explained by NH-mediated His263 interaction absent in N-methylated boldine. In addition, hemisynthetic alkaloids (3BrBOL and DAB) show interactions and affinity energies similar to those of BOL. In HEMn-DP (40ppm, 24h), BOL/3BrBOL achieved 100% tyrosinase inhibition (viability ∼50%), exceeding DAB (62%). MelanoDerm™ (0.1% w/v, 14 days): results confirmed the efficacy of 3BrBOL (-33% melanin, P < 0.05; ∼arbutin), BOL (-10%), and DAB/LTS inactivity, highlighting the superiority of C-3 halogenation. LTS is the premier natural inhibitor; optimization of 3BrBOL validates BOL derivatization for ARB equivalent depigmentation in 3D models. These findings support the development of hydroquinone-free cosmeceuticals from Chilean flora alkaloids and advocate the use of nanoemulsions to enhance delivery and reduce cytotoxicity.

Food additives are widely used to extend the shelf life of foods and maintain their quality. In this study, the potential of Prunus laurocerasus and Prunus cerasifera fruit pits (endocarp and seed) as food additives was investigated in terms of cytotoxicity, antigenotoxicity, antioxidant activity, enzymatic anti-browning, and urease enzyme inhibition, and their phytochemical contents were comprehensively analyzed. While the extracts showed low cytotoxicity against the healthy L929 cell line, they exhibited a concentration-dependent increase in selective cytotoxicity against A549, CaCo-2, Hep3B, MCF-7, and PC-3 cells. Furthermore, the genotoxic safety of the extracts was assessed in both prokaryotic and eukaryotic model test systems. The extracts showed no cytogenotoxic or mutagenic effects in the Allium cepa and Ames/Salmonella assays. P. cerasifera endocarp ethyl acetate extract exhibited the highest antioxidant activity (DPPH, CUPRAC, and TEAC: 576.24, 402.42, and 680.14 mg Trolox g-1 extract, respectively) and strong enzyme inhibition, with tyrosinase (IC50: 10.46 ± 1.48 μg mL-1) nearly comparable to kojic acid and potent urease inhibition (IC50: 28.60 ± 2.08 μg mL-1). Phytochemical analysis of the extracts was performed using liquid chromatography-tandem mass spectrometry, with epicatechin (10.722 mg g-1 extract) detected in the highest amount in the endocarp of P. laurocerasus and quinic acid (11.679 mg g-1 extract) detected in the endocarp of P. cerasifera. Overall, according to the conducted cytotoxicity and genotoxicity assays, P. laurocerasus and P. cerasifera fruit pits were found to be safe, rich in bioactive phytochemicals, and exhibited strong antioxidant and enzyme inhibitory activities, highlighting their potential as sustainable functional ingredients or natural food additives. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Background: Periorbital melanosis (dark circles under the eyes) is a common cosmetic concern that can negatively affect appearance and psychological well-being. Various therapeutic approaches have been explored in cosmetic dermatology for its management. Mandelic acid, an alpha-hydroxy acid derived from bitter almonds, promotes gentle exfoliation and inhibits melanin synthesis, while kojic acid primarily acts as a tyrosinase inhibitor that reduces melanogenesis. Although both agents are widely used in treating hyperpigmentation disorders, comparative clinical evidence regarding their effectiveness in periorbital melanosis remains limited. Objectives: This study aimed to compare the clinical efficacy, safety, and patient satisfaction of a 40% mandelic acid chemical peel with 2% topical kojic acid cream in patients with periorbital melanosis. The study also evaluated changes in pigmentation severity, lesion color characteristics, and overall improvement using standardized clinical grading and a visual analogue scale (VAS) over a 12-week treatment period. Methods: This single-center randomized parallel clinical trial included 20 adult patients with periorbital melanosis recruited from the outpatient dermatology department of Saveetha University Medical College and Hospital. Participants were randomly assigned to two groups. The intervention group received 40% mandelic acid peel applied to the periorbital area every two weeks for six sessions, while the comparator group applied 2% kojic acid cream twice daily for 12 weeks. Pigmentation was evaluated at baseline and week 12 using a 10-point VAS, standardized pigmentation grading (Grades I–IV), and color classification. Safety and tolerability were also monitored. Results: Both groups showed significant improvement in pigmentation after treatment. However, the mandelic acid peel group demonstrated greater clinical improvement, with 40% of patients achieving Grade I reduction and a greater shift toward lighter pigmentation compared with the kojic acid group. VAS scores were significantly higher in the mandelic acid group (p &lt; 0.05). Both treatments were well tolerated, with only mild transient erythema reported and no serious adverse events. Conclusion: Both 40% mandelic acid peel and 2% topical kojic acid are safe and effective for treating periorbital melanosis; however, the mandelic acid peel demonstrated superior efficacy. Its combined exfoliative and anti-melanogenic effects may contribute to faster and more noticeable improvement.

ABSTRACT The escalating crisis of bacterial resistance demands the urgent discovery of novel antibacterial agents. The natural product kojic acid has emerged as a privileged pharmacophore for developing new antibacterial and antibiofilm agents, owing to its excellent metal‐chelating properties and structural versatility. This review aims to provide recent advances in kojic acid‐based derivatives as antibacterial and antibiofilm agents, docking studies, mechanisms of action, and structure‐activity relationships, with emphasis on key optimization strategies such as Mannich base formation, iron‐chelation design, and hybrid conjugation with antibiotics. We discussed the action mechanism of derivatives and antibacterial activity of derivatives against pathogens, including Gram‐positive strains (such as Staphylococcus aureus ) and Gram‐negative strains (such as Pseudomonas aeruginosa ). SARs reveal that the introduction of hydrophobic moieties at the C‐6 position of the hydroxypyranone core is crucial for enhancing activity against gram‐positive bacteria, while modifications at the C‐2 position or the hydroxyl groups primarily influence metal coordination and antibiofilm efficacy. Collectively, we address the current challenges and future directions for this promising class of compounds, offering valuable insights for the rational design of potent antibacterial and antibiofilm agents based on the kojic acid scaffold.

Kojic acid dipalmitate microemulsion ameliorates STZ+HFD-induced metabolic cardiomyopathy via RAGE/Cdc42 pathway.

Guaiane-type sesquiterpenes from Carciofo Bianco di Pertosa, a cultivar of Cynara cardunculus subsp. scolymus (L.), leaf: Isolation and evaluation of tyrosinase inhibitory activity.

Background: Voluntary skin depigmentation is a widespread practice in sub-Saharan Africa and constitutes a major public health concern due to its prevalence and associated complications. Glutathione has emerged as an alternative to conventional depigmenting agents; however, limited data are available regarding its commercialization and regulatory compliance in Central Africa. Objective: To describe the use, composition, and compliance with Cameroonian standards of glutathione-based cosmetic products in Yaoundé. Methods: A descriptive cross-sectional study was conducted between March and April 2020 in three major markets in Yaoundé. Vendors selling glutathione-based cosmetic products were interviewed, and products were inventoried and photographed to assess pharmaceutical form, origin, composition, and labeling compliance according to national standards (NC 804 and NC 814). Results: Forty vendors were included. All were aware of the depigmenting properties of glutathione. Artisanal manufacturing was frequent (65%), with systematic use of glutathione powder. Among 54 identified products, the predominant forms were body milks (31%) and serums (28%), mostly imported from Asia or of unknown origin. Only 9% contained glutathione alone; most combined glutathione with other active ingredients (vitamins C and E, kojic acid). None complied with all mandatory labeling requirements, and specific warnings were rarely mentioned. Conclusion: Glutathione-based products are widely used in Yaoundé, often in artisanal formulations, with insufficient regulatory compliance. These findings provide a valuable baseline for strengthening regulation and surveillance of skin-lightening cosmetics.

Enydra fluctuans Lour. is a perennial herb widely used in traditional Asian medicine; however, the specific therapeutic potential of its essential oil (EO) remains underexplored. This study aimed to determine the chemical profile of E. fluctuans EO via gas chromatography-mass spectrometry (GC-MS). It also evaluated antioxidant potential and inhibitory activities of the EO against α-amylase, α-glucosidase and tyrosinase. The GC-MS analysis revealed a unique, monoterpene-dominated profile (90.75%), with the major constituents including α-limonene (45.33%), β-pinene (22.35%), sabinene (11.70%), β-myrcene (4.58%), and α-pinene (4.42%). The assays showed concentration-dependent inhibitions of the EO against α-amylase and α-glucosidase, with IC50 values of 118.90 ± 1.86 and 61.49 ± 3.39 μg/mL, respectively. The results clearly demonstrated that the EO’s inhibitory activities against the enzymes were comparable to the antidiabetic drug (acarbose). For tyrosinase inhibition, the EO showed a concentration-dependent effect with an IC50 of 347.36 ± 9.51 μg/mL, which was significantly weaker than kojic acid. These findings provide preliminary insights into the bioactivity profile of E. fluctuans EO and support further investigation to clarify its mechanisms of action and biological relevance.

Curcuma zedoaria (Christm.) Roscoe, a traditionally valued plant species of the Zingiberaceae family, possesses notable pharmacological potential but has remained underexplored for its chemotypic characterisation and biological properties. The present study reports a distinct β-curcumene–rich chemotype of essential oil obtained from C. zedoaria rhizomes sampled from Eastern India and aimed to determine its biological activities. GC-MS analysis identified 44 compounds from which β-curcumene (30.78%) was the dominant one, followed by ar-curcumene (29.6%), camphor (6.34%) and xanthorrhizol (5.94%) as the major constituents. β-Curcumene rich novel essential oil chemotype of C. zedoaria acknowledged strong anti-inflammatory outcomes in LPS-mediated RAW 264.7 murine monocytes by substantially decreasing the inducement of NO (84.8%), PGE (83.1%), TNF-α (92.4%), IL-6 (91.7%) and IL-1β (86.0%). Besides, the essential oil illustrated convincing antiproliferative efficacy against MCF7, HepG2 and PC3 cancer cell lines with IC50 values less than 200 µg/mL. MCF7 cells exhibiting an IC50 value of 80.23 ± 1.68 μg/mL showed the highest selective cytotoxicity. C. zedoaria essential oil showed moderate antityrosinase activity exhibiting an IC50 value of 181.28 ± 2.78 μg/mL as compared to the standard kojic acid. All reported biological activities were found to be statistically significant (p < 0.05). The extent of biological activities of phytoconstituents was assessed by in silico PASS prediction analysis, which could be correlated with in vitro studies. Overall, the findings suggest that the β-curcumene–rich essential oil may serve as a promising natural source for pharmaceutical and cosmetic applications, subject to further in vivo and formulation studies.

Tyrosinase is the key rate limiting enzyme that controls melanin production. A series of novel kojic acid-cinnamic acid hybrids (JP1~26) were synthesized as tyrosinase inhibitors. All compounds displayed potential anti-tyrosinase activity with IC50 values of 0.51~1.53 µM, ~ 10-30 folds stronger than control kojic acid. Among them, the strongest inhibitor JP5 inhibited tyrosinase in a mixed-type. Fluorescence quenching, 3D fluorescence, and CD spectra revealed the binding characteristic of JP5 with tyrosinase. Molecular docking displayed their binding detail with catalytic site residues. In addition, JP5 also could inhibit intracellular tyrosinase activity, thence, inhibiting melanin production in B16 cells. Therefore, kojic acid-cinnamic acid hybrids could service as potential tyrosinase inhibitors.

Vitex negundo L. (Verbenaceae) is a well-known medicinal plant used in traditional medicine for the treatment of inflammatory, microbial, and oxidative stress-related disorders. The present study aimed to evaluate antibacterial and antioxidant activities of Vitex negundo leaf extracts, along with their chemical characterization using Fourier transform infrared (FT-IR) spectroscopy and gas chromatography-mass spectrometry (GC-MS). Antibacterial activity of acetone, methanol, and aqueous extracts was assessed by agar well diffusion method against four bacterial strains. The acetone extract exhibited notable antibacterial activity, particularly against Bacillus cereus and Bacillus subtilis. Antioxidant potential was evaluated using the DPPH radical scavenging assay, where acetone and methanol extracts demonstrated the highest activity in a dose-dependent manner. FT-IR analysis confirmed the presence of various functional groups associated with bioactive compounds. GC-MS profiling identified 24 compounds in the acetone extract and 20 compounds in the methanol extract, with major constituents such as isoambreinolide, catechol, n-hexadecanoic acid, kojic acid, karanjin, and phytol, many of which are known for their antimicrobial, antioxidant and anti-inflammatory properties. Overall, the findings indicate that Vitex negundo leaves are rich in bioactive phytochemicals and possess significant antibacterial and antioxidant activities, supporting their traditional medicinal use and highlighting their potential for pharmaceutical applications.