Melanogenesis Inhibitory Activity Research Articles

Anti-melanin and tyrosinase inhibition mechanism of polydatin and 6″-O-lauryl polydatin synthesized by microwave-assisted enzymatic catalysis

Exploiting efficient tyrosinase inhibitors and utilizing the inhibition mechanism are of great significance to avoid enzymatic browning in food and skin melanogenesis. Polydatin had excellent tyrosinase inhibitory activity in vitro with IC50 value of 24.90 μM; however, it exhibited unsatisfactory inhibitory activity intracellularly, which was associated with poor cellular uptake. Fortunately, 6″-O-lauryl polydatin was green-efficiently synthesized by lipase-catalyzed acylation under microwave irradiation. 6″-O-lauryl polydatin exhibited superior mono-/diphenolase inhibitory activity within 100 μM than kojic acid, which had IC50 of 221 μM. Neither polydatin nor 6″-O-lauryl polydatin bound to the catalytic site, but rather bound noncovalently to the allosteric site 2 of tyrosinase through hydrogen bonds and hydrophobic interactions according to molecular simulations, thereby inducing secondary structure unfolding and reducing tyrosinase activity. 6″-O-lauryl polydatin showed stronger anti-browning effects than polydatin in the natural storage of potato and apple pieces. Polydatin and kojic acid did not induce apoptosis, but 6″-O-lauryl polydatin inhibited human melanin A375 cell proliferation by stimulating ROS overproduction and regulating cell cycle and apoptotic pathways. In addition, lipophilic 6″-O-lauryl polydatin had greater cellular uptake though suffered from intracellular hydrolysis, and exerted better tyrosinase and melanogenesis inhibitory activity than polydatin and kojic acid based on mouse B16F10 melanoma cell model. The results suggested polydatin and 6″-O-lauryl polydatin were promising tyrosinase inhibitors for anti-browning in foods or cosmetics fields.

The elastase and melanogenesis inhibitory and anti-inflammatory activities of phosvitin phosphopeptides produced using high-temperature and mild-pressure (HTMP) pretreatment and enzyme hydrolysis combinations

This study aimed to determine the skin protective effect of egg yolk phosvitin phosphopeptides (PPPs). Phosvitin was separated from the egg yolk, and PPPs were produced using high-temperature and mild-pressure (HTMP) pretreatment and enzyme-sterilization hydrolysis combinations. The elastase and melanogenesis inhibitory activities and anti-inflammatory effects of egg yolk PPPs were determined. All PPPs significantly inhibited elastase activity, but the PPPs prepared with HTMP pretreatment and trypsin-sterilization (HTMP-T-S) combination suppressed the tyrosinase activity the most. PPPs (3 mg/mL) inhibited the α-melanocyte-stimulating hormone-induced melanin production in B16F10 melanoma cells by 31.18 to 38.58%. In addition, PPPs effectively inhibited nitric oxide (NO) production in the LPS (lipopolysaccharide)-stimulated RAW 264.7 macrophages, and the PPPs from HTMP-T-S exhibited the highest inhibitory activity. The protein expressions of pro-inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2 were down-regulated by the PPPs from the HTMP-T-S. Therefore, PPPs could be used as an anti-melanogenic, anti-elastase, and anti-inflammatory agent for humans and skin care products.

Metatranscriptomics Reveals Sequential Expression of Genes Involved in the Production of Melanogenesis Inhibitors by the Defined Microbial Species in Fermented Unpolished Black Rice.

Fermented products require metabolic enzymes from the microbial community for desired final products. Using a metatranscriptomic approach, the role of microorganisms in fermented products on producing compounds with a melanogenesis inhibition activity has not yet been reported. Previously, unpolished black rice (UBR) fermented with the E11 starter containing Saccharomyces cerevisiae, Saccharomycopsis fibuligera, Rhizopus oryzae, and Pediococcus pentosaceus (FUBR) showed potent melanogenesis inhibition activity. This study aimed to investigate the function of these defined microbial species in producing melanogenesis inhibitors in the FUBR using a metatranscriptomic approach. The melanogenesis inhibition activity increased in a fermentation time-dependent manner. Genes related to melanogenesis inhibitors synthesis such as carbohydrate metabolism, amino acids synthesis, fatty acids/unsaturated fatty acids synthesis, and carbohydrate transporters were analyzed. Most genes from R. oryzae and P. pentosaceus were upregulated in the early stage of the fermentation process, while those of S. cerevisiae and S. fibuligera were upregulated in the late stage. FUBR production using different combinations of the four microbial species shows that all species were required to produce the highest activity. The FUBR containing at least R. oryzae and/or P. pentosaceus exhibited a certain level of activity. These findings were in agreement with the metatranscriptomic results. Overall, the results suggested that all four species sequentially and/or coordinately synthesized metabolites during the fermentation that led to a FUBR with maximum melanogenesis inhibition activity. This study not only sheds light on crucial functions of certain microbial community on producing the melanogenesis inhibitors, but also paves the way to initiate quality improvement of melanogenesis inhibition activity in the FUBR. IMPORTANCE Fermentation of food is a metabolic process through the action of enzymes from certain microorganisms. Although roles of the microbial community in the fermented food were investigated using metatranscriptomic approach in terms of flavors, but no study has been reported so far on the function of the microorganisms on producing compounds with a melanogenesis inhibition activity. Therefore, this study explained the roles of the defined microorganisms from the selected starter in the fermented unpolished black rice (FUBR) that can produce melanogenesis inhibitor(s) using metatranscriptomic analysis. Genes from different species were upregulated at different fermentation time. All four microbial species in the FUBR sequentially and/or coordinately synthesized metabolites during fermentation that led to a FUBR with maximal melanogenesis inhibition activity. This finding contributes to a deeper understanding of the roles of certain microbial community during fermentation and led to the knowledge-based improvement for the fermented rice with potent melanogenesis inhibition activity.

Emulsion formulated using Hibiscus tiliaceus L. extract and flaxseed oil for topical application

The oil of Linum usitatissimum L., also known as flaxseed, is known for its many health benefits and has been widely used in food and cosmetic product. Hibiscus tiliaceus L. is a semi-mangrove whose wood and bark are used for fuel and fibre production. Preliminary studies have reported tyrosinase and melanogenesis inhibition activity in H. tiliaceus leaves dichloromethane extract (DE). Thus, it was believed that Hibiscus tiliaceus leaves could be used as an active ingredient in whitening products. The present study aimed to develop a stable formulation using flaxseed oil and H. tiliaceus partially purified extract (PE). Furthermore, this study aimed to evaluate the formulations’ physicochemical properties, microbial quality, storage stability, safety, and bioactivities. The presence of the active compound, friedelin, in partially purified extract (PE) obtained using Silica 60 column chromatography was identified using gas chromatography-mass spectrometry (GC-MS) analysis. Emulsions incorporated with 0.1% and 0.2% (w/w) PE, namely partially purified extract emulsion (PEE) 1 and 2 respectively, were found with satisfied physiochemical and safety evaluations. Both PEE 1 and 2 remarkably inhibited tyrosinase activity by 61% and 70%, respectively. They also exerted high efficacy in suppressing melanin content and tyrosinase activity in murine melanoma cells (B16F1). Furthermore, both PEE showed no antiproliferative activity on both melanoma and normal human dermal fibroblast (NHDF) cells and are unlikely to cause inflammation and affect the function of melanoma cells used in the melanogenesis assay. Interestingly, PEE 1 and 2 inhibited 34% and 32% extracellular melanogenesis at 0.5 mg/mL, which was higher than that of 1 and 2 mg/mL. No microbial growth was observed for in the microbial test when incorporating eugenol (0.4%) into the emulsions as an antimicrobial agent. PEE 1 yields better physicochemical properties, microbial quality and bioactivities upon storage at chilled, ambient and elevated temperatures. This study creates an approach to the development of natural whitening products using coastal plants.

Structure-activity relationship study of 4,5-didehydroguadiscine, an aporphine alkaloid showing potent melanogenesis-inhibitory activity in B16 melanoma cells

Although 4,5-didehydroguadiscine (12a), an alkaloid with potent melanogenesis-inhibitory activity isolated from Hornschuchia obliqua (Annonaceae), consists of an aporphine nucleus with an aromatized B-ring, to date, it has not been utilized as a template for structure–activity relationship (SAR) studies of pharmacological activities because of its exceptional structure. Accordingly, herein, five analogs (12b–12f) of 12a and five benzylisoquinoline analogs (13b–13f) lacking the C11a–C11b bond of 12b–12f were prepared. The inhibitory effects of 12b–12f and 13b–13f on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells were examined and compared with those of 12a. Melanogenesis-inhibitory activities of 12b–12f were the same as that of 12a, whereas the melanogenesis-inhibitory activities of 13b–13f were significantly inferior to those of 12a and 12b–12f. These results suggest that the C11a–C11b bond plays an essential role in the melanogenesis-inhibitory activities of 12a–12e.

Self-Assembled pH-Responsive Metal-Organic Frameworks for Enhancing the Encapsulation and Anti-Oxidation and Melanogenesis Inhibition Activities of Glabridin.

Metal organic frameworks (MOFs) are formed by self-assembly of metal ions and organic ligands. A special type of MOF called ZIF-8, which is formed by self-assembly of zinc ions and 2-methylimidazole, shows excellent stability in aqueous solutions and disintegrates under acidic conditions. These properties make ZIF-8 a suitable carrier material for pH-stimulated drug delivery systems. Glabridin is an isoflavane compound that is widely present in the roots of licorice. Because of its outstanding skin whitening properties, glabridin is widely used as a whitener in the cosmetics industry. In this study, ZIF-8 was employed to encapsulate glabridin. Glabridin-loaded ZIF-8 was successfully prepared with a drug encapsulation efficiency of 98.67%. The prepared sample showed a fusiform or cruciate flower-like structure, and its size was about 3 μm. ZIF-8 enabled pH-controlled release of glabridin. Moreover, ZIF-8 encapsulation significantly enhanced the intracellular anti-oxidant activity and melanogenesis inhibitory activity of glabridin. This study provides a new approach that shows great potential to improve the biological application of glabridin.

Characterization of Phenethyl Cinnamamide Compounds from Hemp Seed and Determination of Their Melanogenesis Inhibitory Activity.

Hyperpigmentation is induced by the overactivation of tyrosinase, which is a rate-limiting enzyme in melanogenesis. The defatted extract of hemp (Cannabis sativa L.) seed is known to have inhibitory effects on melanogenesis; however, effective compounds in the extract have not been identified yet. In this study, three phenethyl cinnamamides present in hemp seed extract were prepared by purification and chemical synthesis and were assessed for their inhibitory effect on melanogenesis in B16F10 melanoma cells. A comparison of the anti-melanogenesis and anti-tyrosinase activity of hemp seed solvent fractions revealed that the ethyl acetate fraction possessed the greatest potential for suppressing melanogenesis in melanoma cells by decreasing tyrosinase activity. We tentatively identified 26 compounds in the ethyl acetate fraction by comparing spectroscopic data with the literature. Three phenethyl cinnamamides such as N-trans-caffeoyltyramine, N-trans-coumaroyltyramine, and N-trans-feruloyltyramine present abundantly in the ethyl acetate fraction were prepared and their anti-melanogenesis and anti-tyrosinase activities in melanoma cells were evaluated. We found that N-trans-caffeoyltyramine and N-trans-feruloyltyramine inhibited alpha melanocyte stimulating hormone (α-MSH)-induced melanogenesis without cytotoxicity, while N-trans-coumaroyltyramine inhibited melanogenesis with cytotoxicity. IC50 values of N-trans-caffeoyltyramine, N-trans-feruloyltyramine, and N-trans-coumaroyltyramine for inhibition of α-MSH-mediated tyrosinase activation were 0.8, 20.2, and 6.3 μM, respectively. Overall, N-trans-caffeoyltyramine possessed the strongest anti-melanogenesis activity among the three phenethyl cinnamamides evaluated. The inhibitory effect of N-trans-caffeoyltyramine was verified by determining the melanin content and tyrosinase activity in melanoma after treating the cells with synthetic compounds. Thus, N-trans-caffeoyltyramine isolated from hemp seed extract could be useful in cosmetics as a skin-whitening agent.

Antibacterial, Antioxidant and Melanogenesis Inhibitory Activity of Auraptene, a Coumarin from Ferula szowitsiana Root

The auraptene is a geranyloxyn coumarin found in the Ferula species. The plant is endemic in Central Asia and it is used as a medicinal food in Iran. This research aimed to evaluate the antibacterial, antioxidant, and anti-melanogenic properties of auraptene, a coumarin from Ferula szowitsiana root. The results revealed that auraptene possessed antibacterial activity with minimum inhibitory and minimum bactericidal concentrations ranged from 2.5 up to 10 mg/ml against human pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Salmonella paratyphi, Clostridium perfringens, Staphylococcus aureus). The nitric oxide scavenging activity (IC50: 670.9 µg/ml) showed its moderate antioxidant potential. Similarly, the results of ferric thiocyanate and thiobarbituric acid assays reconfirmed the moderate antioxidant activity of auraptene and indicated the percentage inhibitions of hydroxyl radicals to be 31.87 and 14%, respectively. The cell-based antioxidant evaluation confirmed the antioxidant activity of auraptene through up-regulation of the antioxidant-related genes including superoxide dismutase, catalase, and glutathione peroxidase in the human foreskin fibroblast (HFF). The auraptene has also displayed the anti-melanogenic activity through direct tyrosinase enzyme inhibition (IC50 of 29.7 µg/ml) and could modulate the expression of major melanogenesis-related genes including tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase in the murine melanoma cell line. The auraptene from Ferula szowitsiana root exhibited antibacterial, antioxidant, and melanogenesis inhibitory activities.

Application of Hibiscus cannabinus L. (kenaf) leaves extract as skin whitening and anti-aging agents in natural cosmetic prototype

In Malaysia, the industrial wastes from the Hibiscus cannabinus L. (kenaf) industry, especially leaves, cause challenges in sustainability. The biological activity of kenaf leaves was reported by few previous studies, it is therefore believable that the kenaf leaves extract (KLE) can be used as functional ingredient in cosmetic formulations. Thus, the aim of this study was to develop a natural cosmetic formulation containing KLE and evaluate it physicochemical characteristics, microbiological properties, storage stability, biological activities (antioxidant, antityrosinase, and anti-aging), in vitro cytotoxicity (on normal human dermal fibroblast and B16F10 melanoma cells) and melanogenesis assay (intracellular tyrosinase activity and reduction of melanin production). The results showed that KLE lotion (KLEL) prepared by 15 % kenaf seed oil (KSO) (F2) with 0.1 % w/w KLE yields the best physical and microbiological stability, with no toxicity on human cells. The KLEL also presented antioxidant content up to 1.84 ± 0.07 mg caffeic acid equivalent (CAE)/g and 21.62 ± 0.76 mg catechin hydrate equivalent (CHE)/g for total phenolic content (TPC) and total flavonoid content (TFC), respectively. In addition, the KLEL presented antityrosinase capacity on inhibition of monophenolase (30.28 ± 3.90 %) and diphenolase (11.40 ± 0.29 %) formation, and revealed, for the first time, anti-aging properties by inhibiting collagenase (36.41 ± 0.54 %) and elastase (23.13 ± 1.56 %) activities. Concerning on melanogenesis inhibitory activity, KLEL presented high efficacy in suppressing cellular tyrosinase activity and melanin content on B16F10 cells. Overall, the results from this study are very promising towards the development of natural cosmetic prototypes using kenaf leaves.

Melanogenesis inhibitory activities of Epicatechin-3-O-gallate isolated from Polygonum amphibium L.

This study aimed to investigate the melanogenesis inhibitory activity of epicatechin-3-O-gallate (ECG) isolated from Polygonum amphibium L. ECG was isolated from the ethanol extract of P. amphibium L, and its chemical structure was determined using spectroscopic methods such as LC-ESI-MS, 1D-NMR, and UV spectroscopy. ECG inhibited the melanogenesis of B16F10 cells in a dose-dependent manner. Particularly, it decreased the melanin content by 27.4% at 200 μM concentration, compared with the control, in B16F10 cells, without causing cytotoxicity. It is noteworthy that the expression of three key proteins, including tyrosinase, tyrosinase-related protein-1 (TRP-1), TRP-2, and microphthalmia-associated transcription factor (MITF), involved in melanogenesis, is significantly inhibited by ECG. The ECG isolated in this study caused the inhibition of body pigmentation and tyrosinase activity in vivo in the zebrafish model. These results suggest that the ECG isolated from P. amphibium L. is an effective anti-melanogenesis agent.

Green synthesis of silver nanoparticles using leaf extract of Euphorbia sanguine: an in vitro study of its photocatalytic and melanogenesis inhibition activity

We report on biosynthesis of silver nanoparticles using aqueous leaf extract of Euphorbia sanguinea and its photocatalytic degradation of Congo red dye and melanogenesis inhibition activity of mushroom tyrosine enzyme. Surface Plasmon resonance bands obtained from UV-Vis spectra were within the range 430–436 nm. FT-IR studies reveal the presence of functional groups of the plant metabolites used as stabilizing agents of nanoparticles. The shape of silver nanoparticles is spherical with size ranges about 20–28.8 nm as confirmed by SEM. XRD patterns displayed well-defined crystalline peaks corresponding to the face-centred cubic structures of metallic silver nanoparticles. The results of photocatalysis showed high photocatalytic efficiency of 86% and 90% within 5 min and 60 min, respectively at a rate of solar radiation of in the degradation of Congo red dye. The AgNPs gave dose dependent melanogenesis inhibition activity with IC50 of 71.96 µg/ml, showing non competitive mode of inhibition. Highlights Rapid formation of silver nanoparticles using 0.5 mL extract of Euphorbia sanguinea. AgNPs are spherical, monodispersed and with sizes in the range of 20–29 nm. High photocatalytic efficiency of 86% was obtained within 5 min of solar radiation of AgNPs in the degradation experiment of Congo red dye. First order kinetics with a correlation coefficient of 0.9472 and a rate of 0.0063 min−1 was established for the photocatalytic process. AgNPs showed dose dependent melanogenesis inhibition activity of IC50 71.96 µg/ml .

Metaproteomic investigation of functional insight into special defined microbial starter on production of fermented rice with melanogenesis inhibition activity.

Fermentation of rice grains requires diverse metabolic enzymes to be synchronously synthesized by the microbial community. Although many studies have used a metaproteomic approach to investigate the roles of microorganisms in improving the flavor of fermented foods, their roles in producing compounds with biological activity have not yet been reported. In a previous study the ferment obtained from unpolished black rice (UBR) fermented with a defined microbial starter (De-E11), comprised of Rhizopus oryzae, Saccharomycopsis fibuligera, Saccharomyces cerevisiae, and Pediococcus pentosaceus, (fermented UBR; FUBR) showed a strong melanogenesis inhibition activity in B16F10 melanoma cells. Hence, in this study, the roles of these microorganisms in producing the melanogenesis inhibitor(s) in FUBR was investigated using a metaproteomic approach. The melanogenesis inhibition activity of the FUBR liquid (FR-Liq) was found to increase with longer fermentation times. R. oryzae and S. cerevisiae were the major hosts of proteins related to the biosynthesis of melanogenesis inhibitor(s) in the FUBR. During fermentation, the enzymes involved in the degradation of UBR and in the carbohydrate metabolic process were identified. These enzymes were associated with the process of releasing of bioactive compound(s) from UBR and the synthesis of organic acids from the microorganisms, respectively. In addition, enzymes involved in the synthesis of some known melanogenesis inhibitor(s) and in the degradation of the melanogenesis stimulator (arsenate) were detected. Varying the combination of microorganisms in the De-E11 starter to produce the FR-Liq revealed that all four microorganisms were required to produce the most potent melanogenesis inhibition activity. Taken together with the metaproteomics results, this suggested that the microorganisms in De-E11 synchronously synthesize the FR-Liq with melanogenesis inhibition activity. In conclusion, this information on the metaproteome in FUBR will increase our understanding of the microbial metabolic modes and could lead to knowledge-based improvements in the fermented rice process to produce melanogenesis inhibitor(s).

Biological Activities of Flavonoids from the Wood Extract of Artocarpus heterophyllus L. (Jackfruit)

Background: Artocarpus heterophyllus L. (Jackfruit) has been used traditionally as treatment for inflammation and cancer. The aim of this study was to isolate compounds from A. heterophyllus wood extract and evaluate their biological activities such as anti-tumor promoting effect on Epstein-Barr virus early antigen induction, melanogenesis inhibitory activity on the B16 mouse melanoma 4A5 cell line and cytotoxic activity against three human cancer cell lines (HL60, A549, SK-BR-3). Methods: A. heterophyllus wood was extracted with n-hexane and methanol. The ethyl acetate soluble- fraction separated from the methanol extract was separated and purified with column chromatography to isolate compounds. The structures of isolated compounds were elucidated with spectroscopic methods. These compounds were evaluated for their biological activities. Results: Thirteen known compounds including four prenylflavonoids were isolated from the wood extracts. Nine flavonoids (2, 3, 5-11) exhibited potent anti-tumor promoting activity with IC50 values of 259-296 molar ratio / 32 pmol TPA. Two flavonoids, Norartocarpetin (6) at concentration of 30 μM and cyanomaclurin (11) at the concentration of 100 μM showed melanin content value of 47.6 % and 80.1 %, respectively. Two prenylflavonoids, cudraflavone B (2) and artocarpin (5), showed cytotoxicity against the human cancer cell lines tested. Cudraflavone B (2) showed cytotoxicity against all three human cancer cell lines whereas artocarpin (5) only exhibited cytotoxicity against two out three cell lines testes. The IC50 values were comparable to or better than cisplatin. Conclusion: From the view point of structure activity relationships of the flavonoids isolated, side chains such as prenyl and 3-methyl-1-butenyl moiety were key for their potent biological activities.

Melanogenesis-inhibitory activities of limonoids and tricyclic diterpenoids from Azadirachta indica.

The chemical constituents of the roots and bark of Azadirachta indica were investigated, leading to the isolation of six tricyclic diterpenoids and four limonoids including a new compound, azadirachtin J (4). The structures were elucidated on the basis of NMR spectroscopic techniques, mass spectrometry as well as comparison with the literature. Furthermore, melanogenesis-inhibitory activities of the isolated compounds were evaluated. As a result, compounds 1-3 and 10 exhibited superior inhibitory activities against melanogenesis with no, or almost no, toxicity to the cells (86.5-105.1% cell viability). Western blot analysis showed that compounds 1 and 3 exhibited melanogenesis inhibitory activities in α-MSH-stimulated B16 melanoma cells due to, at least in part, inhibition of the expression of MITF, followed by a decrease in the expression of tyrosinase, TRP-1, and TRP-2. Compounds 1 and 3 exhibited tyrosinase inhibitory activities (IC50 values of 44.86μM and 69.85μM respectively). Docking results confirm that the active inhibitors strongly interact with tyrosinase residues.

Efficient dimerization of (−)-epigallocatechin gallate using nonthermal plasma as potent melanogenesis inhibitors

(−)-Epigallocatechin gallate (EGCG), which is the most abundant bitter polyphenol in green tea (Camellia sinensis) leaves, is generally unstable under oxidative conditions. In this study, the efficient dimerization of EGCG was successfully achieved without changes in stereochemistry by treatment with nonthermal dielectric barrier discharge (DBD) plasma. The stereochemically pure dimers 2 and 3 connected by a methylene linkage exhibited significantly enhanced melanogenesis inhibitory activities compared to the parent EGCG and the active compounds 2 and 3 suppressed cellular tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 expression in B16F10 melanoma cells, which could be considered one of the mechanisms of action. These results indicate a new method for efficient dimerization of stereochemically active depigment agent induced by DBD plasma treatment.

Antimelanogenic Activity of Ocotillol-Type Saponins from Panax vietnamensis.

The ocotillol (OCT)-type saponins have been known as a tetracyclic triterpenoid, possessing five- or six-membered epoxy ring in the side chain. Interestingly, this type saponin was mostly found in Panax vietnamensis Ha et Grushv., Araliaceae (VG), hence making VG unique from the other Panax spp. Five OCT-type saponins, majonoside R2, vina-ginsenoside R2, majonoside R1, pseudoginsenoside RT4, vina-ginsenoside R11, together with three protopanaxadiol (PPD)-type saponins and four protopanaxatriol (PPT)-type saponins from VG were evaluated for their antimelanogenic activity. All of isolates were found to be active. More importantly, the five OCT-type saponins inhibited melanin production in B16-F10 mouse melanoma cells, without showing any cytotoxicity. Besides ginsenoside Rd and ginsenoside Rg3 in PPD and notoginsenoside R1 in PPT-type saponins, majonoside R2 was the most potent melanogenesis inhibitory activity in OCT-type saponins. In this article, we highlighted antimelanogenic activity of OCT-type saponins and potential structure-activity relationship (SAR) of ginsenosides. Our results suggested that OCT-type saponins could be used as a depigmentation agent.

A Promising View of Kudzu Plant, Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep: Flavonoid Phytochemical Compounds, Taxonomic Data, Traditional Uses and Potential Biological Activities for Future Cosmetic Application

Pueraria montana var. lobata is widely known as kudzu especially in Japan, China, Korea, and other Asian countries. This plant is an ingredient for traditional food and an herbal ingredient for traditional medicines, particular in Japan and China. There are a few reports on its cosmetic uses. Interestingly, many phytochemical compounds from this plant have been continuously reported, particularly flavonoid compounds, which are well-known as potential bioactive ingredients for cosmetics. This work aims to illustrate promising views of kudzu plant, focusing on the diversity of flavonoid phytochemical compounds, taxonomic data, traditional uses, and potential biological activities for future cosmetic applications, i.e., antioxidant, antiglycation, skin regeneration, and melanogenesis inhibitory activities.

Structure-activity relationship for vanilloid compounds from extract of Zingiber officinale var rubrum rhizomes: effect on extracellular melanogenesis inhibitory activity

The components in the methanol extract of Zingiber officinale var rubrum (red ginger) were isolated by a series of column chromatography and identified by Nuclear Magnetic Resonance (NMR) and Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOFMS). Thirteen components, including eleven vanilloid compounds, were isolated from the extract. All the isolated components reduced extracellular melanin contents. Structure-activity relationship studies suggested that elongation of the carbon chain of shogaol and gingerol increased the extracellular melanogenesis inhibitory activity, and that the carbonyl and hydroxyl groups on the carbon chain in gingerol played an important role in this effect. In order to reveal the importance of the vanillyl group for the melanogenesis inhibitory activity, 6-gingerol (1) and 6-shogaol (5), which were the main compounds in the extract, were glucosylated and their effects were evaluated. The glucosylated 6-shogaol resulted in improved melanogenesis inhibitory activity, while the glucosylated 6-gingerol had no such effect. These results indicated different mechanisms for the melanogenesis inhibitory activity of the two vanilloid compounds.

Isolation of phenylpropanoid sucrose esters from the roots of Persicaria orientalis and their potential as inhibitors of melanogenesis

Cosmetically, hyperpigmentation is an important issue and the most prominent target for inhibiting hyperpigmentation is, tyrosinase, the rate-limiting enzyme in melanogenesis. Therefore, in this research, we have screened several medicinal plants collected from Bangladesh for their anti-tyrosinase activity and found that roots of Persicaria orientalis have potent inhibitory activity. Nine compounds, including five phenylpropanoid sucrose esters (1–5), were isolated from the EtOH extract of P. orientalis roots. The chemical structures were determined based on spectroscopic methods. All the tested compounds (1–5), significantly reduced extracellular melanin formation in B16 melanoma cells and inhibited tyrosinase monophenolase and diphenolase activity in a dose dependent manner. Compound 4 was twice as effective as kojic acid, when l-DOPA was used as the substrate. Compound 1 and 4 showed better inhibitory activity (>59%) on melanin synthesis at a treated concentration of 50 µM compare with arbutin (730 µM). At 6.25 µM concentration, compounds 2 and 5, inhibited extracellular melanin production by 53.1% and 40.2%, respectively. Structure-activity-relationship suggested that both the feruloyl (C-6′) and acetyl (C-2′/ C-4′) groups in sucrose moiety is essential for cytotoxicity. Our finding indicated the roots of P. orientalis is a potential source of natural compounds that could be used in dermatological and cosmetological research. To the best of our knowledge, this is the first study to report the potential melanogenesis inhibitory activity of phenylpropanoid sucrose esters.

Total Synthesis of γ-Alkylidenebutenolides, Potent Melanogenesis Inhibitors from Thai Medicinal Plant Melodorum fruticosum.

A hitherto unreported member of γ-alkylidenebutenolides in Melodorum fruticosum (Annonaceae), (4 E)-6-benzoyloxy-7-hydroxy-2,4-heptadiene-4-olide, named as isofruticosinol (4) was isolated from the methanol extract of flowers, along with the known related butenolides, namely, the (4 Z)-isomer (3) of 4, melodrinol (1), and its (4 E)-isomer (2). To unambiguously determine the absolute configuration at the C-6 position in these butenolides, the first total syntheses of both enantiomers of 2-4 were achieved over 6-7 steps from commercially available D- or L-ribose (D- and L-5). Using the same protocol, both enantiomers of 1 were also synthesized. Based on chiral HPLC analysis of all synthetic compounds ( S- and R-1-4), all naturally occurring butenolides were assigned as partial racemic mixtures with respect to the chiral center at C-6 (enantiomeric ratio, 6 S/6 R = ∼83/17). Furthermore, the melanogenesis inhibitory activities of S- and R-1-4 were evaluated, with all shown to be potent inhibitors with IC50 values in the range 0.29-2.9 μM, regardless of differences in the stereochemistry at C-6. In particular, S-4 (IC50 = 0.29 μM) and R-4 (0.39 μM) showed potent inhibitory activities compared with that of reference standard arbutin (174 μM).