Tyrosinase is a copper oxidase enzyme which catalyzes the first two steps in the melanogenesis pathway, L-tyrosine to L-dopa conversion and, then, to o-dopaquinone and dopachrome. Hypopigmentation and, above all, hyperpigmentation issues can be originated depending on their activity. This enzyme also promotes the browning of fruits and vegetables. Therefore, control of their activity by regulators is research topic of great relevance. In this work, we consider the use of inhibitors of monophenolase and diphenolase activities of the enzyme in order to accomplish such control. An experimental design and data analysis which allow the accurate calculation of the degree of inhibition of monophenolase activity (iM) and diphenolase activity (iD) are proposed. The IC50 values (amount of inhibitor that causes 50 % inhibition at a fixed substrate concentration) can be calculated for the two activities and from the values of IC50M (monophenolase) and IC50D(diphenolase). Additionally, the strength and type of inhibition can be deduced from these values. The data analysis from these IC50D values allows to obtain the values of [Formula: see text] or [Formula: see text] , or and [Formula: see text] from the values of IC50M. In all cases, the values of the different must satisfy their relationship with IC50M and IC50D.

Human skin pigmentation and melanin synthesis are incredibly variable, and are impacted by genetics, UV exposure, and some drugs. Patients\' physical appearance, psychological health, and social functioning are all impacted by a sizable number of skin conditions that cause pigmentary abnormalities. Hyperpigmentation, where pigment appears to overflow, and hypopigmentation, where pigment is reduced, are the two major classifications of skin pigmentation. Albinism, melasma, vitiligo, Addison\'s disease, and post-inflammatory hyperpigmentation, which can be brought on by eczema, acne vulgaris, and drug interactions, are the most common skin pigmentation disorders in clinical practice. Anti-inflammatory medications, antioxidants, and medications that inhibit tyrosinase, which prevents the production of melanin, are all possible treatments for pigmentation problems. Skin pigmentation can be treated orally and topically with medications, herbal remedies, and cosmetic products, but a doctor should always be consulted before beginning any new medicine or treatment plan. This review article explores the numerous types of pigmentation problems, their causes, and treatments, as well as the 25 plants, 4 marine species, and 17 topical and oral medications now on the market that have been clinically tested to treat skin diseases.

Tyrosinase is a key enzyme target to design new chemical ligands against melanogenesis. In the current review, different chemical derivatives are explored which have been used as anti-melanogenic compounds. These are different chemical compounds naturally present in plants and semi-synthetic and synthetic compounds inspired by these natural products, such as kojic acid produced by several species of fungi; arbutin-a glycosylated hydroquinone extracted from the bearberry plant; vanillin-a phenolic aldehyde extracted from the vanilla bean, etc. After enzyme inhibition screening, various chemical compounds showed different therapeutic effects as tyrosinase inhibitors with different values of the inhibition constant and IC50. We show how appropriately designed scaffolds inspired by the structures of natural compounds are used to develop novel synthetic inhibitors. We review the results of numerous studies, which could lead to the development of effective anti-tyrosinase agents with increased efficiency and safety in the near future, with many applications in the food, pharmaceutical and cosmetics industries.

Tyrosinase is a bifunctional polyphenol oxidase (PPO), catalyzing two oxidative reactions: monophenols to o-quinones (monophenolase activity) and o-diphenols to oquinones (diphenolase activity). As tyrosinase is the rate-limiting enzyme for the melanogenesis process, it is an attractive target for melanogenesis inhibition. Aiming at skin whitening, anticancer, Parkinson\'s disease (PD) treatment, antibacterial, fruit and vegetable preservation and other anti-pigmentation effect, medicinal chemists have exploited diverse tyrosinase inhibitors through various approaches. In addition to discovering inhibitors with novel scaffolds, good activity and high safety, researchers also focused on developing strategies for synergistic effects of multiple inhibitors and simultaneously regulating multiple targets to treat cancer or neurodegenerative diseases. This review focused on multiple natural and synthetic tyrosinase inhibitors, which could contribute to preventing fruit and vegetable browning, skin whitening, antibacterial, anticancer, Parkinson\'s Disease, etc.

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.

Safety concerns are the primary consideration to identify and detection of enzyme inhibitors. In this regard, safe and potent tyrosinase inhibitors play important role in enhancing nutritional quality, health promotion and also prevent further damages. The present review focuses on the recent and efficient tyrosinase inhibitors discovered from both synthetic sources and synthesized phenolic compounds, including flavonoid, carvacrol, thymol, cinnamic acid and resorcinol derivatives. The inhibitory activity of these compounds was analyzed according to chemical structure, IC50, Ki and their binding energy. Further, inhibition mechanism and the biological effects of some these inhibitors with potential application in food, agricultural, cosmetic and pharmaceutical industries were briefly discussed. Molecular docking procedure was performed on some derivatives and demonstrated favorable binding affinity with amino acid residues of mushroom tyrosinase (PDB ID: 2Y9X). The information offered showed that the substitution pattern of hydroxyl groups at the phenyl ring is an important factor of tyrosinase inhibitory activity. The results confirmed that understanding structural modification of inhibitors is a key role in finding novel and efficacious tyrosinase inhibitors.Communicated by Ramaswamy H. Sarma.

Human has used plants to treat many civilisation diseases for thousands of years. Examples include reserpine (hypertension therapy), digoxin (myocardial diseases), vinblastine and vincristine (cancers), and opioids (palliative treatment). Plants are a rich source of natural metabolites with multiple biological activities, and the use of modern approaches and tools allowed finally for more effective bioprospecting. The new phytochemicals are hyaluronidase (Hyal) inhibitors, which could serve as anti-cancer drugs, male contraceptives, and an antidote against venoms. In turn, tyrosinase inhibitors can be used in cosmetics/pharmaceuticals as whitening agents and to treat skin pigmentation disorders. However, the activity of these inhibitors is stricte dependent on their structure and the presence of the chemical groups, e.g. carbonyl or hydroxyl. This review aims to provide comprehensive and in-depth evidence related to the anti-tyrosinase and anti-Hyal activity of phytochemicals as well as confirming their efficiency and future perspectives.

OBJECTIVE: Melanin gives some natural protection against the harmful effects of ultraviolet radiation; however, excessive production of melanin causes skin hyperpigmentation. Depigmenting cosmetics can be used to control this process; however, depigmenting agents commonly used have some disadvantages, such as low bioavailability, photosensitization, cellular toxicity, and insolubility. Natural sources of melanogenic inhibitors have become important alternatives to synthetic ones. The objective of this review was to summarize the results of studies on natural extracts that have been reported in the literature to inhibit the process of melanogenesis, giving a view on their suitability for potential use in new cosmetic formulations for skin-lightening.
METHODS: A systematic literature search was carried out using the descriptors: \"melanogenesis\", \"tyrosinase\", \"tyrosinase inhibition\", and \"natural agents\".
METHODS: Publications were selected based on our designated inclusion and exclusion criteria, and a total of 15 studies met these criteria.
METHODS: The following were used in the review of each paper which met the criteria: the name of the plant (all of the natural extracts turned out to be from plants), the method used to obtain the plant extract, the method for evaluating anti-tyrosinase activity, the main results, and the conclusions.
RESULTS: All evaluated natural agents demonstrated anti-tyrosinase effect. The species Leathesia difformis, Morus alba, Orostachys japonicus, Heracleum moellendorffii, Coix lacryma-jobi (adlay), Inula brittanica, and Gailardia aristata stood out from the others due to their application as potential inhibitors of more than three proteins related to melanogenesis, including the cyclic adenosine monophosphate response element-binding protein, microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, tyrosinase-related protein-2, and dopachrome tautomerase.
CONCLUSIONS: The plants present an anti-tyrosinase effect that must be better explored in the new cosmetic formulations. The anti-melanogenic effects of the plant are mainly related to the presence of phenolic and antioxidant compounds.
OBJECTIVE: La mélanine offre une certaine protection naturelle contre les effets nocifs des rayons ultraviolets ; cependant, une production excessive de mélanine provoque une hyperpigmentation cutanée. Les cosmétiques dépigmentants peuvent servir à contrôler ce processus ; cependant, les agents dépigmentants couramment utilisés présentent certains inconvénients, comme une biodisponibilité faible, une photosensibilité, une toxicité cellulaire et une insolubilité. Les sources naturelles d’inhibiteurs de la mélanogénèse sont devenues des alternatives importantes aux inhibiteurs synthétiques. L’objectif de cette revue était de résumer les résultats des études sur les extraits naturels signalés dans la littérature comme inhibant le processus de mélanogenèse, en donnant un aperçu de leur adéquation à une utilisation potentielle dans de nouvelles formulations cosmétiques pour l’éclaircissement de la peau. SOURCES DES DONNÉES: Une recherche systématique dans la littérature a été réalisée à l’aide des descripteurs : « mélanogenèse », « tyrosinase », ‘inhibition de la tyrosinase » et « agents naturels ». Sélection des études : Les publications ont été sélectionnées d’après nos critères d’inclusion et d’exclusion désignés et un total de 15 études remplissaient ces critères. EXTRACTION DES DONNÉES: Les éléments suivant ont été utilisés dans l’examen de chaque article répondant aux critères : le nom de la plante (tous les extraits naturels se sont avérés provenir des plantes), la méthode utilisée pour obtenir l’extrait végétal, la méthode d’évaluation de l’activité anti-tyrosinase, les principaux résultats et les conclusions. SYNTHÈSE DES DONNÉES: Tous les agents naturels évalués ont démontré un effet anti-tyrosinase. Les espèces Leathesia difformis, Morus alba, Orostachys japonicus, ,Heracleum moellendorffii, Coix lacryma-jobi (adlay), Inula brittanica, et Gailardia aristata se sont distinguées des autres en raison de leur application comme inhibiteurs potentiels de plus de trois protéines liées à la mélanogenèse, dont la protéine de liaison d’élément de réponse d’adénosine monophosphate cyclique, du facteur de transcription associé à la microphtalmie, la tyrosinase, la protéine liée à la tyrosinase-1, la protéine liée à la tyrosinase-2 et la dopachrome tautomérase.
CONCLUSIONS: Les plantes présentent un effet anti-tyrosinase qui doit être exploré plus en profondeur dans les nouvelles formulations cosmétiques. Les effets inhibiteurs de la mélanogénèse des plantes sont principalement dus à la présence de composés phénoliques et antioxydants.

Food allergy has become a major global public health concern. In the past decades, enzymatic crosslinking technique has been employed to mitigate the immunoreactivity of food allergens. It is an emerging non-thermal technique that can serve as a great alternative to conventional food processing approaches in developing hypoallergenic food products, owing to their benefits of high specificity and selectivity. Enzymatic crosslinking via tyrosinase (TYR), laccase (LAC), peroxidase (PO), and transglutaminase (TG) modifies the structural and biochemical properties of food allergens that subsequently cause denaturation and masking of the antigenic epitopes. LAC, TYR, and PO catalyze the oxidation of tyrosine side chains to initiate protein crosslinking, while TG initiates isopeptide bonding between lysine and glutamine residues. Enzymatic treatment produces a high molecular weight crosslinked polymer with reduced immunoreactivity and IgE-binding potential. Crosslinked allergens further inhibit mast cell degranulation due to the lower immunostimulatory potential that assists in the equilibration of T-helper (Th)1/Th2 immunobalance. This review provides an updated overview of the studies carried out in the last decade on the potential application of enzymatic crosslinking for mitigating food allergenicity that can be of importance in the context of developing hypoallergenic/non-allergenic food products.

Numerous dough improvers are used alone or in combination to enhance the quality of baked goods such as breads. While modern consumers demand consistent quality, the expectations for ingredients have changed over the past few years, and reformulations have taken place to provide \"clean label\" options. However, the effects and mechanisms of blended dough conditioners suitable for such baked products have not been systematically summarized. In this review, dough and bread properties as affected by different improver combinations are examined, with a focus on additive or synergistic interactions between enzymes or between enzymes and ascorbic acid. The combination of enzymes that hydrolyze starch and cell wall polysaccharides has been shown to reduce textural hardness in fresh and stored bakes goods such as breads. Enzymes that hydrolyze arabinoxylans, the main nonstarch polysaccharide in wheat, have synergistic effects with enzymes that result in cross-linking of wheat flour biopolymers. In some studies, the effects of bread improvers varied for wheat flours of different strength. Overall, bread products in which wheat is used in whole grain form or in a blend with other flours especially benefit from multiple improvers that target different flour constituents in doughs.