Anti-melanogenesis Activity Research Articles

Bioguided Fractionation and Purification of Natural Bioactives Obtained from<i>Alpinia conchigera</i> Water Extract with Melanin Inhibition Activity

Crude extracts of Alpinia conchigera a species from the Malaysian Ginger (Zingiberaceae) family and its fractions obtained from various extraction methods were assayed for melanogenesis inhibition activity and cell viability. The crude extract obtained from the ethanolic extraction and the super critical fluid extraction did not exhibit significant melanin inhibition activity and was shown to be toxic to the melanocyte cells in comparison to the water extract. The crude aqueous extracts displayed melanin inhibition of 96.38 ± 1.60% and cell viability 109.90 ± 8.32% at a concentration of 500 μg/mL. Bioassay guided fractionation was performed on the water extracts to isolate the active compounds. The actives were identified as trans-cinnamaldehyde and chavicol glucopyranoside with both compound showing potent anti-melanogenesis activity. At 4.9 μg/ml, both trans-cinnamaldehyde and chavicol glucopyranoside gave 85% inhibition of melanin formation in vitro with 77% and 97% cell viability respectively. In comparison, kojic acid, a known skin lightening agent showed 90.0% inhibition at 100 μg/mL. The bioactive composition comprising the extract, active fraction, purified compounds or mixture thereof of Alpinia conchigera may be used for cosmetic and pharmaceutical applications, particularly for the purposes of reducing skin pigmentation.

Design, synthesis, and evaluation of (E)-N-substituted benzylidene–aniline derivatives as tyrosinase inhibitors

We attempted to design and synthesize (E)-N-substituted benzylidene-hydroxy or methoxy-aniline derivatives and to evaluate their inhibitory effect on tyrosinase activity and anti-melanogenesis activity in murine B16F10 melanoma cells. Derivatives with a 4-methoxy- or 4-hydroxy-anilino group exerted more potent inhibition against mushroom tyrosinase than those with a 2-hydroxyanilino group. (E)-4-((4-Hydroxyphenylimino)methyl)benzene-1,2-diol exhibited the most potent and non-competitive inhibition on mushroom tyrosinase showing an IC50 of 17.22 ± 0.38 μM and being more effective than kojic acid (51.11 ± 1.42 μM). This compound decreased melanin production stimulated by the alpha-melanocyte-stimulating hormone and inhibited murine tyrosinase activity in a dose-dependent manner. Therefore, we propose (E)-4-((4-hydroxyphenylimino)methyl)benzene-1,2-diol as a new candidate of potent tyrosinase inhibitors that could be used as therapeutic agent with safe skin-whitening efficiency.

Validation of Eupatorium triplinerve Vahl Leaves, a Skin Care Herb from East Kalimantan, Using a Melanin Biosynthesis Assay

In searching for a new material made from natural resources that could be used as a whitening agent, we focused on the plants used for skin treatment by the native people of East Kalimantan. The methanol extract of the leaves of Eupatorium triplinerve Vahl showed antimelanogenesis activity in a melanin biosynthesis assay. By activity-guided fractionation, 7-methoxycoumarin (1) was isolated as an active compound. The IC50 of 1 on mushroom tyrosinase was 2360μM (L-tyrosine was used as the substrate) and above 2840μM (L-DOPA was used as the substrate), respectively. Regarding melanin formation inhibition in B16 melanoma cells, the IC50 of 1 was 1780μM with 83% cell viability at IC50. Based on these results, we validated that the leaf extract is in line with the traditional use of the Dayak tribe in East Kalimantan.

Melanogenesis Inhibitor(s) fromPhyla nodifloraExtract

Overexpression of tyrosinase can cause excessive production of melanin and lead to hyperpigmentation disorders, including melasma and freckles. Recently, agents obtained from plants are being used as alternative medicines to downregulate tyrosinase synthesis and decrease melanin production. Phyla nodiflora Greene (Verbenaceae) is used as a folk medicine in Taiwanese for treating and preventing inflammatory diseases such as hepatitis and dermatitis. However, the antimelanogenesis activity and molecular biological mechanism underlying the activity of the methanolic extract of P. nodiflora (PNM) have not been investigated to date. Our results showed that PNM treatment was not cytotoxic and significantly reduced the cellular melanin content and tyrosinase activity in a dose-dependent manner (P < 0.05). Further, PNM exhibited a significant antimelanogenesis effect (P < 0.05) by reducing the levels of phospho-cAMP response element-binding protein and microphthalmia-associated transcription factor (MITF), inhibiting the synthesis of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2, and decreasing the cellular melanin content. Moreover, PNM significantly activated the phosphorylation of mitogen-activated protein kinases, including phospho-extracellular signal-regulated kinase, c-Jun N-terminal kinase, and phospho-p38, and inhibited the synthesis of MITF, thus decreasing melanogenesis. These properties suggest that PNM could be used as a clinical and cosmetic skin-whitening agent to cure and/or prevent hyperpigmentation.

Novel phenolic glucoside, origanoside, protects against oxidative damage and modulates antioxidant enzyme activity

Our previous research demonstrated that a novel phenolic glucoside, origanoside, isolated from Origanum vulgare, exhibits significant antimelanogenesis activity. The present study was designed to investigate whether origanoside may serve as a quencher of oxidative insults and is involved in antimelanogenesis. It is found that origanoside exhibit the radical-scavenging capacity of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS+) and superoxide anion radical (O2−), the reducing power, and the inhibition ability of lipid peroxidation (LP). Pretreatment with origanoside in hydrogen peroxide (H2O2)-treated BNLCL2 and HaCaT cells increased the activities of catalase (CAT) and glutathione peroxidase (GPx), potentially reducing the amount of reactive oxygen species (ROS) generation. These findings confirm the cytoprotective effect of origanoside in hepatocytes and keratinocytes, suggesting that origanoside exhibits antioxidant activities and may be a useful food additive.

Refinement of the pharmacophore of 3,4-dihydroquinazoline-2(1 H)-thiones for their anti-melanogenesis activity

In order to define the structural requirements of quinazoline-2(1 H)-thiones 1 for their inhibitory activity on melanogenesis, a novel series of 3,4-dihydroquinazoline-2(1 H)-thiones ( 3a– h) were prepared and screened for their melanogenesis inhibition on melanoma B16 cell line under the stimulant of α-MSH. The anti-melanogenesis activity of 3 is mainly mediated by the hydrogen bonding ability of thioamide unit in addition to complexation ability of thione and the hydrophobic binding power of side chain substitutions at 3-position. Thus, the pharmacophore of 3,4-dihydroquinazoline-2(1 H)-thiones for their anti-melanogenesis activity could be refined as 3-hydrophobic substituted quinazolinethione.

3-Prenyl luteolin, a new prenylated flavone with melanin biosynthesis inhibitory activity from wood of Artocarpus heterophyllus

In our efforts to find new whitening agent from natural resources, we focused on wood of Artocarpus heterophyllus which shows anti-melanogenesis activity. By activity-guided fractionation of A. heterophyllus wood extract, a new prenylated flavonoid, 3-prenyl luteolin ( 1) was isolated. The IC 50 of mushroom tyrosinase inhibitotry activity of 1 was 76.3 µM. The results of the comparison with that of luteolin showed the prenyl substituent at C-3 position of 1 play an important role for revealing tyrosinase inhibition. In melanin formation inhibition on B16 melanoma cells, IC 50 of 1 was 56.7 µM with less cytotoxicity.

Antidermatophyte and antimelanogenesis compound from Eleutherine americana grown in Indonesia

An active compound from the bulb of Eleutherine americana L. Merr. (Iridaceae) collected from East Kalimantan, Indonesia, was tested for its antidermatophyte and antimelanogenesis activity. Antifungal assay-directed fractionation of the n-hexane-soluble fraction of the methanolic extract of the bulb of E. americana led to the isolation of 1 as an active compound. The compound was identified as the naphthoquinone eleutherin by EI-MS and (1)H-, (13)C-, and two-dimensional NMR analyses. Antidermatophyte assay of 1 at concentrations of 10, 20, 40, 60, and 80 microg/disk and myconazole, a commercial antidermatophyte, at 10 microg/disk displayed 7, 8, 13, 16, 17, and 14 mm of inhibition zone against Trichophyton mentagrophytes, respectively. In a melanin formation inhibition assay, compound 1 displayed potent antimelanogenesis activity at 5 ppm with low toxicity compared with arbutin, a commercial skin-whitening agent. The results showed the high potential of 1, an active compound from E. americana, to be applied as an antidermatophyte and antimelanogenesis agent.

Bioactive monoterpene glycosides conjugated with gallic acid from the leaves of Eucalyptus globulus

Two monoterpene glycosides, conjugated with gallic acid [globulusin A ( 1) and B ( 2)], together with four known compounds, cypellocarpin A ( 3), eucaglobulin ( 4), cuniloside ( 5) and (1 S, 2 S, 4 R)- trans-2-hydroxy-1,8-cineole β- d-glucopyranoside ( 6), were isolated from hot-water extracts of the leaves of Eucalyptus globulus. The structures of compounds 1 and 2 were determined by 1D, 2D NMR and MS spectroscopic analyses. The absolute stereochemistry of 1 was determined by correlating the spectroscopic data with those of synthetic compound 6 with a known configuration. Globulusin A ( 1) and B ( 2), cypellocarpin A ( 3) and eucaglobulin ( 4), scavenged DPPH free radicals and globulusin A ( 1) showed a higher antioxidant activity than the other tested compounds, with an IC 50 of 3.8 μM. Globulusin A ( 1) and eucaglobulin ( 4) concentration-dependently suppressed inflammatory cytokine production, tumor-necrosis factor-α and interleukin-1β in cultured human myeloma THP-1 cells co-stimulated with phorbol myristate acetate. These compounds also inhibited melanogenesis in cultured murine melanoma B16F1 cells, without any significant cytotoxicity. These results suggested that globulusin A ( 1) and eucaglobulin ( 4), which were isolated as antioxidants from E. globulus, also had anti-inflammatory as well as anti-melanogenesis activity.

Changing paradigms in dermatology: science and art of diagnostic patch and contact urticaria testing

This study was conducted to evaluate preparation and characteristics of flexible liposomes (Bounsphere™) consisting of a biocompatible lipid membrane with dipotassium glycyrrhizate (DPG) as an edge activator and containing niacinamide (NA). We evaluated particle size and zeta potential of the prepared liposomes by dynamic light scattering (DLS), and investigated their deformability, safety, skin permeability, and anti-melanogenesis activity in Bounsphere™ that remained stable for more than 6 months. The average size of Bounsphere™ was about 200 nm, and the change in liposome size after 6 months was not greater than that of conventional liposomes. The zeta potential of Bounsphere™ was about 32 mV with a positive charge, indicating relatively good stability. The deformability of Bounsphere™ was higher than that of conventional liposomes. In addition, the skin permeability of Bounsphere™ was higher than that of conventional liposomes or the phosphate buffer solution. These results indicated that Bounsphere™ with DPG as an edge activator has advantages over conventional liposomes as NA carriers. Furthermore, we found that 2% NA-loaded Bounsphere™ enhanced skin whitening. Taken together, our results demonstrate that Bounsphere™ can be used as a delivery system to enhance transdermal permeation and skin whitening agent effectiveness.