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Swertiajaponin is a competitive inhibitor of tyrosinase. The binding affinity of (A) kojic acid or (C) swertiajaponin with tyrosinase (Agaricus bisporus, PDB ID:2Y9X) predicted by protein docking simulation using AutoDock Vina. LigandScout 3.1 software was applied to investigate binding residues of tyrosinase that interact with (B) kojic acid or (D) swertiajaponin. (E) The Lineweaver-Burk plot analysis was done to examine the mode of inhibition by swertiajaponin. (F) Km is the Michaelis-Menten constant and Vmax is the maximum reaction velocity based on Lineweaver-Burk plot analysis.
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Many skin-whitening compounds target tyrosinase because it catalyzes two rate-limiting steps in melanin synthesis. Although many tyrosinase inhibitors are currently available for a skin–whitening purpose, undesirable adverse effects are also reported. Thus, numerous efforts have been made to develop safer tyrosinase inhibitors from natural products...
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... test this, protein- ligand docking simulation was performed to predict binding affinity using AutoDock Vina. The predicted binding affinity between tyrosinase and kojic acid was -5.4 kcal/mol and the affinity between tyrosinase and swertiajaponin was -6.3 kcal/mol ( Figure 4A and 4C), suggesting that swertiajaponin may bind to tyrosinase with stronger affinity than kojic acid www.impactjournals.com/oncotarget Hs27 cells treated with various doses of swertiajaponin (2-20 μM) for 48 h. ...
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... further investigate the binding mode between compounds and tyrosinase, pharmacophore analysis was performed using LigandScout 3.1 software. While kojic acid may bind to tyrosinase mainly via hydrogen bonds with the ASN260 or GLU256 residue of tyrosinase ( Figure 4B), swertiajaponin forms multiple hydrogen bonds with HIS85, ASN81, ASN260, HIS244, and ARG268 residues of tyrosinase and hydrophobic interactions with MET257, VAL248, and PHE264 residue of tyrosinase ( Figure 4D), which likely explains the higher binding affinity of swertiajaponin to tyrosinase. ...
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... further investigate the binding mode between compounds and tyrosinase, pharmacophore analysis was performed using LigandScout 3.1 software. While kojic acid may bind to tyrosinase mainly via hydrogen bonds with the ASN260 or GLU256 residue of tyrosinase ( Figure 4B), swertiajaponin forms multiple hydrogen bonds with HIS85, ASN81, ASN260, HIS244, and ARG268 residues of tyrosinase and hydrophobic interactions with MET257, VAL248, and PHE264 residue of tyrosinase ( Figure 4D), which likely explains the higher binding affinity of swertiajaponin to tyrosinase. ...
Citations
... Bobrov. Analysis of the extracts revealed the presence of about 40 bioactive compounds, including chlorogenic acid (see Figure 11), swertiajaponin (a well-known skin-whitening flavonoid derivative which inhibits both activity and protein expression levels of tyrosinase) [57], and isoorientin (the 6-C-glucoside of luteolin) (Figure 12), those most present and to which the antioxidant, anti-inflammatory, antibacterial, and anti-acne activities are presumably attributed. In particular, the ethanolic extract of the aerial parts of C. uralensis showed the best biological activity profile (i.e., substantial inhibition of COX-1 and COX-2, good radical scavenging properties, and, most importantly, no toxicity on normal skin fibroblasts), although the antibacterial activity against all tested bacterial strains tested (S. aureus, S. epidermidis, and C. acnes) was moderate [25]. ...
In recent years, there has been a growing interest in the use of medicinal plants and phytochemicals as potential treatments for acne vulgaris. This condition, characterized by chronic inflammation, predominantly affects adolescents and young adults. Conventional treatment typically targets the key factors contributing to its development: the proliferation of Cutibacterium acnes and the associated inflammation. However, these treatments often involve the use of potent drugs. As a result, the exploration of herbal medicine as a complementary approach has emerged as a promising strategy. By harnessing the therapeutic properties of medicinal plants and phytochemicals, it may be possible to address acne vulgaris while minimizing the reliance on strong drugs. This approach not only offers potential benefits for individuals seeking alternative treatments but also underscores the importance of natural remedies of plant origin in dermatological care. The primary aim of this study was to assess the antimicrobial, antioxidant, and anti-inflammatory properties of plants and their phytochemical constituents in the management of mild acne vulgaris. A comprehensive search of scientific databases was conducted from 2018 to September 2023. The findings of this review suggest that medicinal plants and their phytochemical components hold promise as treatments for mild acne vulgaris. However, it is crucial to note that further research employing high-quality evidence and standardized methodologies is essential to substantiate their efficacy and safety profiles.
... Functioning as an inhibitor of melanin accumulation, brassinin achieves this by reducing the mRNA level of tyrosinase, which occurs through the inhibition of melanocyte-inducing transcription factor (MITF) translocation [35]. Tyrosinase serves as a critical enzyme in the initial stages of melanogenesis, while MITF acts as an essential transcription factor regulating tyrosinase [63,64]. ...
Indole phytoalexins, found in economically significant Cruciferae family plants, are synthesized in response to pathogen attacks or stress, serving as crucial components of plant defense mechanisms against bacterial and fungal infections. Furthermore, recent research indicates that these compounds hold promise for improving human health, particularly in terms of potential anticancer effects that have been observed in various studies. Since our last comprehensive overview in 2016 focusing on the antiproliferative effects of these substances, brassinin and camalexin have been the most extensively studied. This review analyses the multifaceted pharmacological effects of brassinin and camalexin, highlighting their anticancer potential. In this article, we also provide an overview of the antiproliferative activity of new synthetic analogs of indole phytoalexins, which were synthesized and tested at our university with the aim of enhancing efficacy compared to the parent compound.
... The Figure 11), swertiajaponin (a well-known skin-whitening flavonoid derivative which inhibits both activity and protein expression levels of tyrosinase) [39], and isoorientin (the 6-C-glucoside of luteolin) (Figure 12), those most present and to which the antioxidant, antiinflammatory, antibacterial, and anti-acne activities are presumably attributed. In particular, the ethanolic extract of the aerial parts of C. uralensis showed the best biological activity profile (i.e., substantial inhibition of COX-1 and COX-2, good radical scavenging properties, and, most importantly, no toxicity on normal skin fibroblasts), although the antibacterial activity against all tested bacterial strains tested (S. aureus, S. epidermidis, and C. acnes) was moderate [40]. ...
In recent years, there has been a growing interest in the use of medicinal plants and phytochemicals as potential treatments for acne vulgaris. This condition, characterized by chronic inflammation, predominantly affects adolescents and young adults. Conventional treatment typically targets the key factors contributing to its development: the proliferation of Cutibacterium acnes and the associated inflammation. However, these treatments often involve the use of potent drugs. As a result, the exploration of herbal medicine as a complementary approach has emerged as a promising strategy. By harnessing the therapeutic properties of medicinal plants and phytochemicals, it may be possible to address acne vulgaris while minimizing the reliance on strong drugs. This approach not only offers potential benefits for individuals seeking alternative treatments but also underscores the importance of natural remedies in dermatological care. The primary aim of this study was to assess the antimicrobial, antioxidant, and anti-inflammatory properties of plants and their phytochemical constituents in the management of mild acne vulgaris. A comprehensive search of scientific databases was conducted from 2018 to September 2023. The findings of this review suggest that medicinal plants and their phytochemical components hold promise as treatments for mild acne vulgaris. However, it is crucial to note that further research employing high-quality evidence and standardized methodologies is essential to substantiate their efficacy and safety profiles.
... Tyrosinase is a key enzyme responsible for melanogenesis [35]. To investigate whether brassinin (Figure 1a) can be applied to a whitening agent, a test tube-based tyrosinase activity assay was performed using mushroom tyrosinase. ...
Brassinin is a phytoalexin abundant in plants, especially in cabbage, and has been reported to act as an anti-cancer and anti-inflammatory agent. However, limited studies are available to elucidate the functionalities of brassinin. Here, we tested the effects of brassinin on melanogenesis using cell-free and cell-based biochemical analysis and docking simulation. Cell-free experiments exhibited that brassinin has antioxidant and anti-tyrosinase activities. When applied to B16F10 cells stimulated with a melanogenesis inducer α-MSH, brassinin pretreatment significantly reduced melanin accumulation and cellular tyrosinase activity. Docking simulation indicates that the docking score of brassinin to the binding pocket of tyrosinase is better than that of kojic acid or arbutin, anti-melanogenic positive controls, indicating that brassinin inhibits melanogenesis at least partially by binding to and inactivating tyrosinase. In addition, qPCR results showed that brassinin reduced tyrosinase mRNA levels. Together, these results suggest that brassinin exerts anti-melanogenesis effects by inhibiting both the activity and mRNA expression levels of tyrosinase. Therefore, our study showed that brassinin has the potential to be used in pharmaceutical or cosmetic products for depigmentation.
... And kojic acid and arbutin were also used as positive controls. The values of the kinetic constants were calculated using Lineweaver-Burk plot analysis, and the maximum velocity (Vmax) and Michaelis constant (K m ) were also calculated by the Lineweaver-Burk plots with the various concentration of L-DOPA substrate [22]. ...
Although melanogenesis is a defense mechanism against ultraviolet (UV)-induced skin damage, abnormally excessive melanin production causes pigmentation disorders. Tyrosinase, as a key factor for melanin synthesis, plays an important role in inducing skin pigmentation. Therefore, the inhibition of tyrosinase is crucial in preventing skin pigmentation in the cosmetics and medicine fields. However, the majority of well-known tyrosinase inhibitors have been discontinued due to toxic effects on the skin or lack of selectivity and/or stability. In this study, we evaluated possible anti-melanogenic effects of catechin-7-O-α-L-rhamnopyranoside (C7R) isolated from the stem bark of Ulmus parvifolia, to discover a new tyrosinase inhibitor that has both safety and stability. When C7R was pretreated in B16F10 melanoma cells stimulated by α-melanocyte-stimulating hormone, this compound reduced melanin accumulation and murine tyrosinase activity. In line with these results, C7R inhibits tyrosinase purified from a mushroom in vitro like kojic acid and arbutin. Furthermore, C7R exhibited a competitive inhibition on a Lineweaver-Burk plot. Next, the underlying mechanisms of the C7R-mediated tyrosinase inhibitory effect were sought through docking simulation and pharmacophore analysis between tyrosinase residues and C7R. The results of these analyses showed that C7R had binding energy of -14.5kcal/mol, and indicated that C7R interacts with tyrosinase through an aromatic ring and various hydrophobic and hydrogen bonds. Together, our results suggest that C7R can be applied as a novel natural anti-melanogenic agent that inhibits tyrosinase.
... The mushroom tyrosinase activity was measured by the oxidation of o-diphenol (L-DOPA) to o-quinone and dopachrome. Briefly (Lee et al., 2017), 80 μL of 0.1 M potassium phosphate buffer (pH 6.8) was prepared in a 96-well plate. Next, 10 μL of test samples or solvents were added before being mixed with 10 μL of mushroom tyrosinase (200 units/mL in buffer). ...
Many medicinal plants such as a Panax ginseng and Morus alba (mulberry tree) have been widely used as depigmenting agents in Asia. To maximize their synergistic effects on melanogenesis, new herbal decoctions were created by mixing Ginseng Radix Alba (GR) and Mori Radicis Cortex (MC) at a ratio of 3:2 which called GMC decoction. A decoction of GR and Mori Ramulus (MR), which called GMR, was also formulated in order to compare the anti-melanogenic capacity. Combined decoctions, GMC and GMR, significantly decreased mushroom tyrosinase activity in vitro; however, single extracts, including MC and MR, showed weaker inhibitory activity. Melanin content assay and Fontana–Masson staining confirmed that two decoctions showed stronger inhibitory effects on the forskolin-induced melanin level in B16 cells, without cytotoxicity. Our findings suggest that ginseng in combination with mulberry tree enhances the anti-melanogenic effect in vitro.
... The up-regulation of the expression and the activity of the microphthalmia-associated transcription factor regulating the gene transcription of tyrosinase as well as activation of the cyclic AMP-protein kinase A pathway were the supposed underlying mechanisms. In a comparative study of the tyrosinaseinhibitory activities of fifty flavonoids, the antioxidant flavone swertiajaponin demonstrated the most potent inhibitory activity against mushroom tyrosinase, with an IC 50 value of 43.47 µM, comparable to the positive control kojic acid, with an IC 50 value of 41.26 µM [36]. Swertiajaponin (6-C-β-D-glucopyranosyl-7-O-methylluteolin) (17), abundant in Swertia japonica and Cymbopogon citratus, demonstrated significant inhibition of skin pigmentation in a human skin model in addition to the depression of melanin accumulation in αMSHor UVB-induced B16F10 cells. ...
Tyrosinase is a multifunctional copper-containing oxidase enzyme that initiates melanin synthesis in humans. Excessive accumulation of melanin pigments or the overexpression of tyrosinase may result in skin-related disorders such as aging spots, wrinkles, melasma, freckles, lentigo, ephelides, nevus, browning and melanoma. Nature expresses itself through the plants as a source of phytochemicals with diverse biological properties. Among these bioactive compounds, flavonoids represent a huge natural class with different categories such as flavones, flavonols, isoflavones, flavan-3-ols, flavanones and chalcones that display antioxidant and tyrosinase inhibitor activities with a diversity of mechanistic approaches. In this review, we explore the role of novel or known flavonoids isolated from different plant species and their participation as tyrosinase inhibitors reported in the last five years from 2016 to 2021. We also discuss the mechanistic approaches through the different studies carried out on these compounds, including in vitro, in vivo and in silico computational research. Information was obtained from Google Scholar, PubMed, and Science Direct. We hope that the updated comprehensive data presented in this review will help researchers to develop new safe, efficacious, and effective drug or skin care products for the prevention of and/or protection against skin-aging disorders.
... New research has shown that swertiajaponin and maclurin in herbs are also powerful ABA action on sliced potato [58,59], via suppressing the generation of reactive oxygen species (ROS) in vitro [60]. In vitro study, Maclurin limited the generation of ROS by about 80% and repressed the EB of the potato for a prolonged period of about five weeks, whereas AA decreased it by approximately 43%. ...
The second-largest cause of losing quality in vegetables and fruits (VFs) is enzymatic browning (EB). As a result of polyphenol oxidases (PPOs), EB leads to the color performance of vegetable and fruit yields. To inhibit the activity of PPOs, chemical and physical methods have been developed and several synthetic chemical compounds are widely used as Anti-Browning Agents (ABA) in VFs products. In recent times, emphasis was placed on customer-oriented food manufacturing innovations. Customers have a tendency to encourage the usage of PPO inhibitors that are natural and environmentally friendly. The aim of present review is to illustrate the underlying mechanisms of PPO chemical inhibitor anti browning action and current trends in some of these inhibitor studies. Studies developed over the last decade have been reported and discussed, such as Natural, chemical, physical, controlled atmosphere and coating techniques to avoid EB. The purpose of this review article will be to assemble and reveal an up-to-date demonstration of browning inhibiting natural and synthetic compounds. The details available in this review could also take to facilitate the ultimate objective of developing new inhibitors of enzymatic browning (plant extracts, natural and synthetic compounds) that are acceptable, healthy and beneficial for the food industry.
... Skin color is considered important in the contexts of fashion and beauty, but the overproduction of melanin due to, for example, excessive UV exposure results in hyperpigmentation, spots, freckles, and melasma [16][17][18][19][20]. Melanin is biosynthesized in the melanosomes of melanocytes by complicated enzymatically driven processes. ...
The β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold confers tyrosinase inhibitory activity, and in the present study, 16 (Z)-5-(substituted benzylidene)-3-phenyl-2-thioxooxazolidin-4-one analogues containing this scaffold were synthesized. Mushroom tyrosinase inhibitory activities were examined. Compound 1c (IC50 = 4.70 ± 0.40 μM) and compound 1j (IC50 = 11.18 ± 0.54 μM) inhibited tyrosinase by 4.9 and 2.1-fold, respectively, and did so more potently than kojic acid (IC50 = 23.18 ± 0.11 μM). Kinetic analysis of tyrosinase inhibition revealed that 1c and 1j inhibited tyrosinase competitively. Results of docking simulation with mushroom tyrosinase using four docking programs suggested that 1c and 1j bind more strongly than kojic acid to the active site of tyrosinase and supported kinetic findings that both compounds are competitive inhibitors. The docking results of human tyrosinase homology model indicated that 1c and 1j can also strongly inhibit human tyrosinase. EZ-cytox assays revealed 1c and 1j were not cytotoxic to B16F10 melanoma cells. The effects of 1c and 1j on cellular tyrosinase activity and melanin production were also investigated in α-MSH- and IBMX-co-stimulated these cells. Both compounds significantly and dose-dependently reduced tyrosinase activity, and at 10 µM were more potent than kojic acid at 20 µM. Compounds 1c and 1j also inhibited melanogenesis, which suggested that the inhibitory effects of these compounds on melanin production were mainly attributable to their inhibitions of tyrosinase. These results indicate that compounds 1c and 1j with the PUSC scaffold have potential use as whitening agents for the treatment of hyperpigmentation-associated diseases.
... In the 3D human skin model, which included human melanocytes and keratinocytes, administration of swertiajaponin (10-20 µM) reduced the level of melanin in the epidermis. Docking studies revealed that the compound directly inhibits enzyme activity by forming multiple hydrogen bonds and hydrophobic interactions in the binding site of the enzyme [37]. ...
Melanogenesis is simply defined as production of melanin in melanosomes by melanocytes through a complex process. Melanin, a pigment derived from L-tyrosine, comes into two forms, namely eumelanin (brownish to black) and pheomelanin (red to yellow). Melanin synthesis starts via the hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine (DOPA) catalyzed by the enzyme known as tyrosinase (TYR), which triggers further conversion reaction to DOPAquinone and then to DOPAchrome. Additionally, this process is also related to two more proteins, i.e. oxygenase TYR-related protein 1 (TYRP1), and dopachrome tautomerase TYRP2 (or DCT). However, TYR located in the melanosomal membrane still stands as the key enzyme to initiate the whole process of melanogenesis. Due to some deficits, melanogenesis may emerge as hypo- or hyperpigmentation in the skin. High production of melanin in melanocytes leads to hyperpigmentationrelated skin disorders including freckles, melasma, melanoma, etc., that may cause displeasure in personal appearance and reduction of quality of life. Consequently, several melanogenesis inhibitors of synthetic and natural origins have been developed up to date, though most of them have been reported with serious side effects. For this reason, an extensive research is still going on to find novel and more effective melanogenesis inhibitors with less side effects. In this sense, particularly flavonoids, catechins, and stilbenes from plants have been a hope to discover new inhibitors which attract a great attention from scientists. In this review, promising natural products effective in melanogenesis inhibition will be scrutinized.
