Euonymus alatus Twig Extract Protects against Scopolamine-Induced Changes in Brain and Brain-Derived Cells via Cholinergic and BDNF Pathways.

In the current study, the therapeutic and preventive effects of Euonymus alatus (EA) twig extract were investigated in a mouse model of cognitive deficit and B35 cells. Twig extract 1 was extracted with 70% ethanol and later twig extract 2 was extracted through liquid-liquid extraction with 70% ethanol and hexane. EA twig 2 (300 mg/kg) along with the standard drug donepezil (5 mg/kg) were orally administered to the mice for 34 days. Scopolamine was given intraperitoneally for 7 days. Administration of EA twig extract 2 significantly improved the passive avoidance test (PAT) in mice. EA twigs extract also restored the scopolamine-reduced brain-derived neurotrophic factor (BDNF)/extracellular regulated kinase (ERK)/cyclic AMP responsive element binding protein (CREB) signaling in B35 cells and the mouse hippocampus. In addition, EA twig extract significantly inhibited the acetylcholine esterase (AChE) activity in B35 cells in a dose-dependent manner. Chromatography and ESI MS analysis of EA twig extract revealed the presence of flavonoids; epicatechin, taxifolin, aromadendrin, and naringenin with catechin being the most abundant. These flavonoids exerted protective effects alone and had the possibility of synergistic effects in combination. Our work unmasks the ameliorating effect of EA twig extract 2 on scopolamine-associated cognitive impairments through the restoration of cholinergic systems and the BDNF/ERK/CREB pathway.

Isolated isoquercitrin from Green ball apple peel inhibits photoaging in CCD-986Sk fibroblasts cells via modulation of the MMPs signaling.

BACKGROUND: Ultraviolet B (UVB) irradiation is viewed as the main factor of skin aging, associated with acceleration of elastin, collagen degradation and expression of matrix metalloproteinases (MMPs). Apples are one of the most commonly eaten fruits in the world, and isoquercitrin is the main active ingredient in new bred varieties "Green ball" apple. Therefore, we are studying the functionality of the active ingredient of apple, a natural raw material that does not have toxicity or sensitivity problems. OBJECTIVES: The aim of this study, we scrutinized the effects of isoquercitrin on skin photoaging in UVB-exposed human fibroblasts (CCD-986Sk). METHODS: To investigate the inhibition effect on photoaging factor regulation, isolated isoquercitrin were treated with UVB, which induces photoaging-related factors in CCD-986Sk fibroblast cells. Pro-inflammatory factors were measured by ELISA, Western blotting and real-time PCR. RESULTS: Isoquercitrin exhibited antioxidant activity and UVB-induced generation of photoaging-related factor inhibition without showing any toxicity. Anti-photoaging effect for protein levels using Isoquercitin was competent, of both the combate MMP-1 and MMP-9. Also, effect of COL1A2 product significantly increase, from up regulating the TIMP-1 mediated pathway in CCD-986Sk cells via the inhibition of MMPs. Isoquercitrin also downregulated the mRNA gene expression of MMPs while upregulating type I procollagen, HAS2 by modulating TIMP-1 and TGF-ß in UVB-irradiated CCD-986Sk cells. CONCLUSIONS: Collectively, our results show that isoquercitrin might be useful as a functional food while being a good candidate in the development of cosmetic products and medicines for the remedy of UVB-induced skin photoaging.

Anti-Inflammatory Effects of Phenolic Compounds Isolated from Quercus Mongolica Fisch. ex Ledeb. on UVB-Irradiated Human Skin Cells.

Quercus mongolica Fisch. ex Ledeb. (QM) has been used as an oriental traditional medicine to relieve hemorrhoids, fever, and enteritis. We screened the inhibitory activities of the extracts and compounds (1-6) isolated from QM on the production of inflammatory cytokines and chemokines to evaluate their anti-inflammatory activities. Further, we evaluated the expression levels of cytokines, chemokines, and immune factors on pedunculagin (PC, 1), which was selected from isolated compounds (1-6) because of its potential anti-inflammation effect. Additionally, we evaluated whether the inflammation mitigation effects of PC (1) following UVB exposure in keratinocytes occurred because of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT)/Janus kinase (JAK) activation. PC (1) remarkably suppressed interleukin (IL)-6, IL-10, IL-13, and monocyte chemoattractant protein-1 (MCP-1) mRNA expression and reduced the mRNA expression level of Cyclooxygenase-2 (COX-2) and also reduced the phosphorylation of p38 mitogen-activated protein kinases (p38), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in a concentration-dependent manner.

Potential effect of compounds isolated from Coffea arabica against UV-B induced skin damage by protecting fibroblast cells.

Ultraviolet (UV) radiation has adverse effects on extracellular matrix (ECM) proteins, leading to formation of wrinkles a hallmark of premature skin aging. The adverse effects of UV radiation are associated with induction of matrix metalloproteinases (MMPs) expression and degradation of collagen and elastin. The present study investigated anti-wrinkle effects of chlorogenic acid (CGA), pyrocatechol (PC) and 3,4,5-tricaffeoyl quinic acid (TCQ), isolated from beans of Coffea arabica, against UV-B stimulated mouse fibroblast cells (CCRF) by measuring expression levels of MMP-1, 3, 9, and type-I procollagen. The three compounds were isolated and purified from coffee grounds using column chromatography and structural examination was evaluated by nuclear magnetic resonance (NMR) analysis. Among the three isolated compounds, CGA effectively suppressed the expression of the MMP-1, 3, and 9 and increased synthesis of type-I procollagen as compared UV-B-stimulated CCRF cells. In addition, CGA dose-dependently inhibited intracellular reactive oxygen species (ROS) production in CCRF cells stimulated by UV radiation. Moreover, CGA displayed a good sun protection factor (SPF) and in vitro DNA damage protection together with inhibition of enzyme xanthine oxidase. The enzyme inhibitory kinetic behavior of CGA was determined by Lineweaver-Burk plot, displayed a mixed type enzyme inhibition with 260.3±4.5µM, Ki value. The results indicate that CGA has potential to be used as a preventive agent against premature skin aging induced by UV radiation.

Anti-inflammatory Potential of Quercetin-3-O-ß-D-("2"-galloyl)-glucopyranoside and Quercetin Isolated from Diospyros kaki calyx via Suppression of MAP Signaling Molecules in LPS-induced RAW 264.7 Macrophages.

Diospyros kaki (DK) contains an abundance of flavonoids and has been used in folk medicine in Korea for centuries. Here, we report for the first time the anti-inflammatory activities of Quercetin (QCT) and Quercetin 3-O-ß-("2"-galloyl)-glucopyranoside (Q32G) isolated from DK. We have determine the no cytotoxicity of Q32G and QCT against RAW 264.7 cells up to concentration of 50 µM. QCT and Q32G demonstrated potent anti-inflammatory activities by reducing expression of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and mitogen-activated protein kinase (MAPKs) in mouse RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Both QCT or Q32G could decrease cellular protein levels of COX-2 and iNOS as well as secreted protein levels of NO, PGE2 , and cytokines (TNF-α, IL-1ß, and IL-6) in culture medium of LPS-stimulated RAW 264.7 macrophages. Immunoblot analysis showed that QCT and Q32G suppressed LPS-induced MAP kinase pathway proteins p-p38, ERK, and JNK. This study revealed that QCT and Q32G have anti-inflammatory potential, however Q32G possess comparable activity as that of QCT and could be use as adjuvant to treat inflammatory diseases.

Quercetin-3-O-ß-d-glucopyranosyl-(1 → 6)-ß-d-glucopyranoside suppresses melanin synthesis by augmenting p38 MAPK and CREB signaling pathways and subsequent cAMP down-regulation in murine melanoma cells.

In this study, the effect of purified quercetin-3-O-ß-d-glucopyranosyl-(1 â†’ 6)-ß-d-glucopyranosid (QCGG) on melanogenesis was investigated. QCGG was isolated from the calyx of a traditional Korean medicinal herb, Persimmon (Diospyros kaki). The hypopigmentation effects of QCGG were determined by examination of cellular melanin contents, tyrosinase activity assay, cAMP assay, and Western blotting of α-MSH-stimulated B16F10 mouse melanoma cells. Our results showed that QCGG inhibited both melanin synthesis and tyrosinase activity in a concentration-dependent manner as well as significantly reduced the expression of melanogenic proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1, tyrosinase-related protein-2, and tyrosinase. Moreover, QCGG inhibited intracellular cAMP levels, cAMP response element-binding protein (CREB), and p38 MAPK expression in α-MSH-stimulated B16F10 cells. Taken together, the suppressive effects of QCGG on melanogenesis may involve down-regulation of MITF and its downstream signaling pathway via phosphorylation of p38 MAPK and CREB along with reduced cAMP levels. These results indicate that QCGG reduced melanin synthesis by reducing expression of tyrosine and tyrosine-related proteins via extracellular signal-related protein kinase (ERK) activation, followed by down-regulation of CREB, p38, and MITF.

Inhibition of matrix metalloproteinase-1 and type-I procollagen expression by phenolic compounds isolated from the leaves of Quercus mongolica in ultraviolet-irradiated human fibroblast cells.

The aim of this study was to investigate the effect of Quercus mongolica (QM) which induce anti-photoaging process of skin in vitro. Bioassay-guided isolation of 80 % Me2CO extract of the leaves of QM led to the isolation and identification of six known phenolic compounds: pedunculagin (1), (-)-epigallocatechin (2), (+)-catechin (3), quercetin 3-O-(6″-O-galloyl)-ß-D-glucopyranoside (4), kaempferol-3-O-ß-D-glucopyranoside-7-O-α-L-rhamnopyranoside (5) and kaempferol 3-O-(6″-galloyl)-ß-D-glucopyranoside (6). The effects of compounds 1-6 on expression of matrix metalloproteinase-1 (MMP-1) and type-I procollagen were further evaluated. Among them, compound 1 showed potent inhibitory effect on MMP-1 and the increased type-I procollagen synthesis in ultraviolet B-induced human fibroblast. These results suggest that pedunculagin, an ellagitannin, is a potential candidate for the prevention and treatment of skin aging.

CopA3 peptide prevents ultraviolet-induced inhibition of type-I procollagen and induction of matrix metalloproteinase-1 in human skin fibroblasts.

Ultraviolet (UV) exposure is well-known to induce premature aging, which is mediated by matrix metalloproteinase-1 (MMP-1) activity. A 9-mer peptide, CopA3 (CopA3) was synthesized from a natural peptide, coprisin, which is isolated from the dung beetle Copris tripartitus. As part of our continuing search for novel bioactive natural products, CopA3 was investigated for its in vitro anti-skin photoaging activity. UV-induced inhibition of type-I procollagen and induction of MMP-1 were partially prevented in human skin fibroblasts by CopA3 peptide in a dose-dependent manner. At a concentration of 25 µM, CopA3 nearly completely inhibited MMP-1 expression. These results suggest that CopA3, an insect peptide, is a potential candidate for the prevention and treatment of skin aging.

Anti-inflammatory activity of sulfate-containing phenolic compounds isolated from the leaves of Myrica rubra.

Three sulfated phenolic compounds, juglanin B (11R)-O-sulfate (1), myricetin 3´-O-sulfate (2), and ampelopsin 3´-O-sulfate (3), were isolated from the leaves of Myrica rubra. Compound 1 was a new sulfated lignan, 2 was a new sulfated flavone, and 3 was a known sulfated flavone. The structures of the new compounds (1 and 2) were determined by acid hydrolysis and spectroscopic methods, including IR, FAB-MS, 1D and 2D NMR. The inhibitory activities of compounds 1-3 and their hydrolysates (1a-3a) against LPS-induced cytokine (TNF-α, IL-1ß, and IL-6) production in macrophage RAW 264.7 cells were evaluated. The 2 new compounds (1 and 2) and their aglycones (1a and 2a) significantly reduced LPS-induced expression of iNOS and COX-2 proteins.

Anti-oxidative and anti-inflammatory activities of caffeoyl hemiterpene glycosides from Spiraea prunifolia.

Activity guided isolation of a Spiraea prunifolia extract yielded five caffeoyl hemiterpene glycosides: 4'-(6-O-caffeoyl-ß-D-glucopyranosyl)-2'-methyl butyric acid, 1-O-caffeoyl-6-O-(4'-hydroxy-2'-methylene-butyroyl)-ß-D-glucopyranoside, 1,2-O-dicaffeoyl-6-O-(4'-hydroxy-2'-methylene-butyroyl)-ß-D-glucopyranoside, 1-O-caffeoyl-6-O-(4'-caffeoyl-2'-methylene-butyroyl)-ß-D-glucopyranoside, and 1-O-caffeoyl-6-O-(4'-caffeoyl-3'-hydroxy-2'-methylene-butyroyl)-ß-D-glucopyranoside, and nine known compounds. Structures were elucidated by analysis of 1D and 2D NMR spectra and FAB-MS. To evaluate the anti-oxidative and anti-inflammatory properties of all fourteen compounds, DPPH radical scavenging, NBT superoxide scavenging, and inhibition of nitric oxide production in LPS-stimulated RAW264.7 cells were examined. Three of the caffeoyl hemiterpene glycosides exhibited potent anti-oxidative and anti-inflammatory activities compared with Vitamin C and l-NMMA, which were used as positive controls.

Flavonoid constituents in the leaves of Myrica rubra sieb. et zucc. with anti-inflammatory activity.

The leaves of Myrica rubra sieb. et zucc. have been used in oriental traditional medicine for the treatment of burns, skin diseases, and as an antidiarrheal in China, Japan, and Korea. Activity guided isolation of the leaves of M. rubra has led to the isolation of five flavonoid: myricetin (1), myricitrin (2), myricetin 3-O-(2″-O-galloyl)-α-L-rhamnopyranoside (3), myricetin 3-O-(2″-O-galloyl)-ß-D-galactopyranoside (4), and quercetin 3-O-(2″-O-galloyl)-ß-D-galactopyranoside (5). All isolates were evaluated for their antioxidant potency against the superoxide anion (O2 (-)), and compounds 3-5 showed potent scavenging activities with 50 % inhibition concentration (IC50) values compared to the positive control, allopurinol. Compounds 1-5 were evaluated as inhibitors of various macrophage functions involved in the inflammatory process. These five compounds significantly and dose dependently inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO), pro-inflammatory cytokines, and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Our results suggest that galloyl flavonol glycosides (3-5) isolated from M. rubra might be beneficial for the treatment of inflammation-related diseases.

Anti-oxidative and anti-proliferative activity on human prostate cancer cells lines of the phenolic compounds from Corylopsis coreana Uyeki.

Fifteen phenolic compounds, including three caffeoyl derivatives, four gallotannins, three ellagitannins and five flavonoids, were isolated from an 80% MeOH extract of the leaves of Corylopsis coreana Uyeki (Korean winter hazel; CL). The anti-oxidative activities [1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase superoxide scavenging activities (NBT)] and the anti-proliferative activity on human prostate cancer cell lines (DU145 and LNCaP) were also evaluated.

Three new orcinol-conjugated hydrolysable tannins from the leaves of Cleyera japonica.

Three new orcinol (3-hydroxy-5-methylphenol)-conjugated hydrolysable tannins, together with two known compounds were isolated from the leaves of Cleyera japonica (CJ), and have been tentatively named cleyeratannin A (1), cleyeratannin B (2) and cleyeratannin C (3). The chemical structures of these compounds were elucidated using 1 dimensional (1D)/2D NMR and high resolution FAB-MS, and the absolute configuration was confirmed by circular dichroism (CD). To evaluate their anti-oxidative activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH)/free radical scavenging activity and nitroblue tetrazolium (NBT)/superoxide anion scavenging activity were determined.

Two new hemiterpene glycosides from the leaves of Ilex rotunda. Thunb.

Chromatographic separation of the 80% MeOH extract of the leaves of Ilex rotunda (IR) led to isolation of two new hemiterpene glycosides, tentatively named as rotundarpenoside A (1) and rotundarpenoside B (2), along with five known caffeoyl derivatives (3-7). The chemical structures of these compounds were elucidated using 1D/2D NMR, HR-MS, and the absolute configuration was confirmed by Mosher's method. In order to evaluate their anti-oxidative activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase superoxide scavenging activities (NBT) were determined.

The antioxidant and anti-inflammatory effects of phenolic compounds isolated from the root of Rhodiola sachalinensis A. BOR.

Isolation of compounds from the root of Rhodiola sachalinensis (RRS) yielded tyrosol (1), salidroside (2), multiflorin B (3), kaempferol-3,4'-di-O-ß-D-glucopyranoside (4), afzelin (5), kaempferol (6), rhodionin (7), and rhodiosin (8). Quantification of these compounds was performed by high-performance liquid chromatography (HPLC). To investigate the antioxidant and anti-inflammatory effects of the compounds, DPPH radical scavenging, NBT superoxide scavenging and nitric oxide production inhibitory activities were examined in LPS-stimulated Raw 264.7 cells. We suggest that the major active components of RRS are herbacetin glycosides, exhibiting antioxidant activity, and kaempferol, exhibiting anti-inflammatory activity.

Effect of Alnus japonica extract on a model of atopic dermatitis in NC/Nga mice.

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.