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Camellia nut shell was collected, dried at room temperature and ground to get fine powder. The powder was extracted three times with 95% EtOH, combined, evaporated, and then freeze dried. The crude powder was dissolved in H2O and then sequentially fractionated with n-hexane, CH2Cl2, EtOAc and n-BuOH. A part of EtOAc fraction was chromatographed on a silica gel and on a Sephadex LH-20 columns using MeOH, aqueous MeOH, EtOAc-n-hexane and EtOH-n-hexane to isolate gallotannins. Three gallotannins, 1,2-di-O-galloyl-β-D-glucopyranoside (2), 1,2,6-tri-Ogalloyl- β-D-glucopyranoside (3) and 1,2,3,6-tetra-O-galloyl-β-D-glucopyranoside (4), including gallic acid (1), were isolated and elucidated by NMR and Mass spectroscopies. Although nothing new, these gallotannins were first reported from the nut shell extractives of camellia tree (Camellia oleifera C. Abel). This study was to investigate the chemical constituents, especially hydrolysable tannins, of nut shell extractives of Camellia oleifera and to provide basic information for the future chemical utilization of this species.

Nowadays, many people prefer products containing functional substances extracted by using harmless extraction methods from environmentally friendly substances. In addition, according to the aging of the population, it consumes a lot in external parts regardless of gender. Accordingly, in this study, we would like to check the whitening function by applying extracts from Ulmus davidiana by supercritical fluid extraction method to melanocytes (B16F10) cells in order to utilize it as a functional material. Here, USCF was extracted from Ulmus davidiana branch (with barks) by supercritical extraction fluid and USCFR was extracted with 60% alcohol at room temperature and filtered from the residues acquired after supercritical extraction. USCFREA was fractionated with ethyl acetate, and the ethyl acetate layer extract was concentrated under vacuum concentration and freeze-drying to obtain final product. First, it was confirmed that the optimal concentration of DMSO for melanocytes was 1% or less. In addition, by using the extracts from the Ulmus davidiana, the melanin content for extracellular and intracellular was checked, and the best effect of melanin treatment was confirmed in sample 2 treated with 50 µg.

As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.

The roots of Rosa multiflora Thunberg have been used in traditional oriental medicine as remedies for rheumatic arthralgia and scabies. In this study, the anti-fungal, anti-oxidant, and anti-inflammatory activities of a supercritical extract of Rosa multiflora root were investigated in vitro. To investigate the anti-oxidant and anti-inflammatory effects of the supercritical extract, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging activity, and the inhibition of nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells were examined, respectively. In addition, the anti-fungal activities of the extract were assessed. The results showed a concentration-dependent, increase in ABTS radical scavenging activity. The supercritical fluid extracts of Rosa multiflora root exhibited low toxicity to RAW 264.7 cells at 100 µg/mL the highest concentration tested. Cells stimulated with LPS produced more nitric oxide than normal control cells; however, cells treated with the supercritical fluid extract decreased this production in a concentration-dependent manner. Finally, the supercritical fluid extracts showed significant anti-fungal activity. These results suggest that extracts of the roots of Rosa multiflora might be used to develop potent anti-fungal, anti-oxidant, and anti-inflammatory agents, and may be useful as ingredients for related new functional cosmetic materials.

Myung Joo Kang1,Jae Yoon Eum1, Mi Sook Jeong2, Sang Han Park1, Ki Young Moon1, Mean Hyung Kang1, Min Soo Kim1, Sun Eun Choi1, Min Won Lee1, Do Ik Lee1, Hyoweon Bang2, Chung Soo Lee2, Seong Soo Joo3, Kapsok Li2, Mi-Kyung Lee2, Seong Jun Seo2, Young Wook Choi11College of Pharmacy, ChungAng University, Heuksuk-dong, Dongjak-gu, Seoul, 2College of Medicine, Chung-Ang University, Heuksukdong, Dongjak-gu, Seoul, 3Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung, South KoreaBackground: The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T).Methods: HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed.Results: EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils.Conclusion: A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD.Keywords: hirsutenone, elastic liposomes, atopic dermatitis, NC/Nga mice, Tat peptide

Recently, the isolation of several condensed tannins from the roots of Rosa multiflora Thunberg, a traditional herbal therapy in oriental medicine for rheumatoid arthritis and scabies, was described. Two of the major condensed tannins – procyanidin B-3 (ProB3) and ent-guibourtinidol-(4β 6)-catechin (RM-1) – were then applied topically to atopic dermatitis-like skin lesions on NC/Nga mice in order to assess their immunomodulatory properties. Both ProB3 and RM-1 significantly reduced the serum levels of eosinophils, IgE and certain Th2 cytokines (IL-4, 5 and 13) (p

The roots of Rhododendron mucronulatum Turzaninov have been used in Oriental traditional medicine for the treatment of dysuria, fever, increase of digestive activity and tonics in China and Korea. Activity guided isolation of the roots of Rhododendron mucronulatum Turzaninov has led to the isolation of three flavonoids, one flavan 3-ol and one proanthocyanidin. Chemical investigation of the 80% Me2CO extract from the roots of Rhododendron mucronulatum led to the isolation and identification of five compounds: taxifolin (1), taxifolin 3-O-β-d-glucopyranoside (2), quercetin 3-O-α-l-arabinofuranoside (3), (-)-epicatechin (4), procyanidin B-3 (5). To investigate the antioxidative and antiinflammatory effects of these compounds, their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated HaCaT cells were also quantified by western blotting and their end products, nitric oxide (NO) and prostaglandin E2 (PGE2), respectively. Compounds (1–5) showed potent DPPH radical scavenging compared with positive controls (l-ascorbic acid). Also, compounds 1 and 2 dose-dependently inhibited the expressions of inflammatory mediators, NO and PGE2, suggesting they are promising candidates as antiinflammatory agents. Copyright © 2011 John Wiley & Sons, Ltd.

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the inflammatory and immune responses, and apoptosis in skin diseases, such as atopic dermatitis. Dysregulated apoptosis is associated with various pathologic conditions, including inflammation and cancer in skin. Polyphenols, including flavonoids and tannins, have been shown to have anti-oxidant, anti-inflammatory and anti-tumor effects. However, the effect of acertannin on TRAIL-induced apoptosis in keratinocytes has not been determined. To assess the preventive effect of acertannin on apoptosis-mediated skin inflammation, we investigated the effect of acertannin on TRAIL-induced apoptosis in human keratinocytes. TRAIL induced nuclear damage, decreased Bid, Bcl-2, Bcl-xL and survivin protein levels, increased Bax levels, induced cytochrome c release, activated caspases (-8, -9 and -3) and increased tumor suppressor p53 levels. Acertannin prevented the TRAIL-induced formation of reactive oxygen/nitrogen species, apoptosis-related protein activation and cell death. The results suggest that acertannin may reduce apoptotic effect of TRAIL on human keratinocytes by suppressing the activation of the caspase-8- and Bid-pathways and the mitochondria-mediated apoptotic pathway, leading to caspase-3 activation. The preventive effect of acertannin on TRAIL-induced apoptosis may be associated with the inhibitory effect on formation of reactive oxygen/nitrogen species. Acertannin may prevent the TRAIL-induced apoptosis-mediated skin inflammation.

The needles of Pinus densiflora Siebold et Zuccarini, a representative Pinus species that grows in Korea, have been used in oriental traditional medicine as remedies for rheumatitis, hemorrhage, cancer, etc. Phytochemical examination of the needles of Pinus densiflora Siebold et Zuccarini led to the isolation of four lignans, one flavan-3-ol, two flavonols and one organic acid. They were identified as icariside E(4) (1), cupressoside A (2), schizandriside (3), (+)-isolariciresinol (4), (+)-catechin (5), quercetin 3-O-β-D-glucopyranoside (6), 5,7,8,4'-tetrahydroxy-3-methoxy-6-methylflavone 8-O-β-D-glucopyranoside (7) and (-)-shikimic acid (8). In order to evaluate the anti-inflammatory effects of these compounds, their inhibitory activities against nitric oxide and prostaglandin E(2) production in IFN-γ- and lipopolysaccharide-stimulated RAW 264.7 cells were examined.

Increased levels of eosinphils, IgE, IL-4, 5, and 13 and pro-inflammatory factors (COX-2, iNOS) are observed in patients with atopic dermatitis (AD). Taxifolin 3-O-beta-D-glucopyranoside (TAX) from the roots of Rhododendron mucronulatum (RM) was examined to determine whether its immunomodulatory effect was applicable for treating atopic dermatitis.A total of 7 groups of NC/Nga mice with AD were treated by topical application or intraperitoneal injection of TAX for 4 weeks. Follow-up evaluations were done to assess the changes in clinical observations, eosinophil counts, and levels of IgE, cytokines, COX-2 and iNOS.In the clinical observation during the experimental period, TAX treatment significantly reduced the severity of AD-like lesions induced in NC/Nga mice. Eosinophil and IgE levels decreased after treatment of the animals with TAX. TAX may thus be associated with improvement of eosinophil-related allergic diseases. The expression of cytokines (IL-4, 5 and 13) was significantly inhibited in the TAX-treated group, suggesting that TAX might play an immunoregulatory role associated with AD. In RT-PCR, iNOS and COX-2 expression levels were reduced in the TAX-treated group. In western blotting, the expression levels of iNOS and COX-2 were also reduced in the TAX-treated group.These findings suggest that TAX is effective for the treatment of AD by preventing the production of inflammatory cytokines and by reducing skin inflammation.

The diarylheptanoid, oregonin (ORE), which was isolated from the bark of Alnus japonica Steudel that grows natively in Korea, has been known to exert antioxidative, anti-inflammatory, anti-cancer and immune response inhibitory effects. The antioxidative effect of ORE was observed on the superoxide and 1,1-diphenyl-2-picrylhydrazyl radical, as well as on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated RAW264.7 macrophages. The statistically significant inhibitory action of ORE against production of cytokines induced by bacterial products or by interleukin (IL)-1beta, free radicals and nitrogen species, and a corresponding increase in cellular calcium concentration because of ORE were confirmed in bone marrow and spleen dendritic cells that are known to play important functions in the development and advancement of atopic dermatitis (AD). It was thus expected that ORE would exert a beneficial effect in the treatment of AD. A study on the pharmaceutical benefits of ORE against AD has not yet been conducted in vivo. We therefore used an in vivo AD animal model, namely the NC/Nga mice, and by applying ORE onto the animals through skin application as well as intraperitoneal injection, we attempted to evaluate the benefits of ORE in this system. Evaluation of ORE was conducted by following the SCORE method to score the effect, as well as by measuring the Th2 cytokines IL-4, IL-5 and IL-13 levels from serum and lymphocytes, and IgE and eosinophil levels from serum. Additionally, the expression of mRNA and protein levels was estimated using real-time polymerase chain reaction and Western blotting analysis. The following categories of clinical evaluation, Th2 cytokines IL-4, IL-5 and IL-13 values, serum IgE levels, serum eosinophil levels, and mRNA and protein expression levels of iNOS and COX-2, were evaluated from topical application and intraperitoneal injection groups of ORE. The effects of ORE on AD in NC/Nga mice were confirmed as being similar to the positive control group, while a significant difference with the negative control group was observed. The results presented in this report suggest that ORE might be beneficial in the treatment of AD.

The aim of the present study was to investigate whether hirsutenone affects the human ether-a-go-go related gene (hERG) K(+) channels. Many drugs promote formation of the acquired form of long QT syndrome (LQTS) by blocking the hERG K(+) channels. Hirsutenone, a new candidate for the treatment inflammatory skin lesions, induced a concentration-dependent decrease in hERG K(+) current amplitudes. Hirsutenone significantly decreased the time constants at the onset of inactivation. However, the reductions in the time constants of steady-state inactivation and the recovery from inactivation after hirsutenone treatment were not significant. In addition, the drug had no effect on the voltage-dependent activation curve or the steady-state inactivation curve. In summary, hirsutenone potentially acts as a blocker of hERG K(+) channels functioning by modifying the channel inactivation kinetics.

Three new stereoisomers of condensed tannins (1—3), and four known phenolic compounds (4—7) were isolated from the 80% acetone extract of the roots of Rosa multiflora Thunberg. The structures of these compounds were elucidated using 1D/2D NMR, high resolution (HR)-MS, and circular dichroism (CD) spectra. In order to evaluate their anti-oxidative and anti-inflammatory activities, their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and inhibitory activity on nitric oxide (NO) production were determined.

Aim of the study The bark of Alnus species has long been used in traditional oriental medicine in the treatment of many pathological conditions, including fever, hemorrhage, diarrhea, alcoholism, various skin diseases (e.g. chronic herpes, eczema and prurigo), and inflammation. In order to assess the immunomodulatory efficacy of a novel herbal medicine in treating atopic dermatitis, we measured serum levels of several allergic and inflammatory biomarkers in NC/Nga mice before and after treatment with this experimental agent. Materials and methods Gene and protein expression analyses of iNOS and COX-2 were quantified by real time PCR and Western blot analysis and serum levels of IL-4, -5 and -13 were also measured by ELISA, all of which were reduced after treatment with the experimental agent. Additionally, serum concentrations of IgE and blood eosinophil counts were reduced in treated mice. Results The topical application of leaf and bark extract from Alnus japonica suppressed the development of AD-like skin lesions. The percent of blood eosinophils was decreased after treatment with leaf and bark extract from Alnus japonica. The serum IgE and Th2-related cytokine levels were decreased after treatment with leaf and bark extract from Alnus japonica compared with those treated with base cream (vehicle treated AD group). The IL-4, IL-5 and IL-13 were lower than those of vehicle treated AD group. Conclusions We contend that leaf and bark extract from Alnus japonica may prove useful in the treatment of atopic dermatitis and other allergic skin diseases, although more in-depth clinical studies are necessary before clinical implementation.

To develop an external preparation of oregonin (ORG) for the treatment of atopic dermatitis (AD), conventional creams (CC) and elastic liposomes (EL) containing ORG have been formulated and examined for their in vitro skin permeation properties and in vivo therapeutic efficacy assessments. EL, consisting of soybean phosphatidylcholine and Tween 80 (85 : 15 w/w %), were of flexible nanocarriers: they were about 130 nm in size and had a 4-fold greater deformability index than conventional liposomes. In a skin permeation study using a Franz diffusion cell mounted with depilated mouse skin, liposomal systems were superior to cream, revealing greater flux values. Both CC and EL were diversified with the addition of Trans-activating transcriptional activator (Tat) peptide, a sort of cell penetrating peptide, and subjected to in vivo efficacy evaluations in NC/Nga mice with AD-like lesions. On clinical observation for skin severity, rapid and profound improvement was observed in the treatment group with Tat-added liposomes (EL/T), showing a significant difference (p

Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing prevalence and severity of AD have prompted the developments of safer, more effective drugs. Although topical corticosteroids have been used as first line therapy for AD, their potential side effects limit their clinical applications. To investigate the effect of hirsutenone (HIR), a diarylheptanoid compound, on AD-like skin lesions and other factors related to immune response is the aim of this paper Th2-related cytokines (IL-4, IL-5, IL-13), eosinophil, IgE inflammatory factors (COX-2, iNOS) levels were reduced in blood, lymphocytes, and tissue after HIR treatment. These results suggest that HIR might be an effective treatment for AD.

Activity guided fractionation of Aconitum koreanum root extract (RAK), a traditional medicine in Korea, afforded four caffeoyl derivatives, caffeic acid (1), 4,5-dicaffeoylquinic acid (2), 3,5-dicaffeoylquinic acid (3) and 3,5-dicaffeoylquinic acid methyl ester (4). In order to evaluate the anti-oxidative and anti-inflammatory effects of these compounds, their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and abilities to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 were examined. And the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated HaCaT cells were also quantified by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Compounds (1-4) showed potent DPPH radical scavenging and NO inhibitory activities as compared with positive controls (L-ascorbic acid and N(G)-monomethyl-L-arginine (L-NMMA), respectively). Also, these compounds dose-dependently inhibited the expressions of iNOS and COX-2 as well as their mRNA levels.

Antigen-presenting dendritic cells may play an important role in the pathogenesis of atopic dermatitis. Taxifolin is demonstrated to have anti-inflammatory effects. The present study was designed to assess the effect of taxifolin glycoside against stimulated responses of dendritic cells isolated from mouse bone marrow and spleen. Dendritic cells exposed to lipopolysaccharide, lipoteichoic acid or interleukin (IL)-1β exhibited increased production of IL-12 p70 and tumour necrosis factor alpha, increased formation of reactive oxygen species (ROS) and nitric oxide (NO), and elevation of intracellular Ca2+ levels. Treatment with taxifolin glycoside inhibited responses stimulated by the microbial products or IL-1β in dendritic cells in a dose-dependent manner. Taxifolin glycoside had a significant inhibitory effect on the production of cytokines, formation of ROS and NO, and change in intracellular Ca2+ levels in dendritic cells of bone marrow and spleen. The results show that taxifolin glycoside seems to inhibit the dendritic cell responses stimulated by microbial products and IL-1β, suggesting that taxifolin glycoside may exert an inhibitory effect against dendritic-cell-mediated immune responses.

The diarylheptanoids (1-10) 1,7-bis-(3,4-dihydroxyphenyl)-heptane-3-O-beta-D-glucopyranosyl(1-->3)-beta-D-xylopyranoside (1), 1,7-bis-(3,4-dihydroxyphenyl)-heptane-3-O-beta-D-apiofuranosyl(1-->6)-beta-D-glucopyranoside (2), 1,7-bis-(3,4-dihydroxyphenyl)-heptane-5-O-beta-D-glucopyranoside (3), 1,7-bis-(3,4-dihydroxyphenyl)-5-hydroxyheptane (4), 1,7-bis-(3,4-dihydroxyphenyl)-heptane-3-one-5-O-beta-D-glucopyranoside (5), oregonin (6), hirsutanonol (7), hirsutenone (8), 1,7-bis-(3,4-dihydroxyphenyl)-5-hydroxyheptane-3-O-beta-D-xylopyranoside (9), and platyphylloside (10), isolated from the bark of Alnus japonica, were analyzed for their cytotoxic activities on various human and mouse cancer cell lines. The cytotoxic activities of these ten compounds were evaluated against murine B16 melanoma, human SNU-1 gastric cancer, human SNU-354 hepatoma cancer and human SNU-C4 colorectal cell lines. The diarylheptanoids showed potent cytotoxic activities against murine B16 melanoma cells and human SNU-C1 gastric cancer cell when the cell viability was analyzed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay.

Taxifolin glycoside is a new drug candidate for the treatment of atopic dermatitis (AD). Many drugs cause side effects such as long QT syndrome by blocking the human ether-a-go-go related gene (hERG) K(+) channels. To determine whether taxifolin glycoside would block hERG K(+) channels, we recorded hERG K(+) currents using a whole-cell patch clamp technique. We found that taxifolin glycoside directly blocked hERG K(+) current in a concentration-dependent manner (EC(50)=9.6±0.7 µM). The activation curve of hERG K(+) channels was negatively shifted by taxifolin glycoside. In addition, taxifolin glycoside accelerated the activation time constant and reduced the onset of the inactivation time constant. These results suggest that taxifolin glycoside blocks hERG K(+) channels that function by facilitating activation and inactivation process.