Seon Il Jang

Anti-Inflammatory and Antipruritic Effects of Luteolin from Perilla (P. frutescens L.) Leaves

Perilla (Perilla frutescens L.) leaves have shown therapeutic efficacy in the treatment of inflammatory disorders, allergies, bronchial asthma, and systemic damage due to free radicals. In the present study we analyzed the active constituents in perilla leaves using high-performance liquid chromatography (HPLC) and isolated luteolin, a polyphenolic flavonoid. We investigated the anti-inflammatory and antipruritic properties of luteolin. Luteolin inhibited the secretion of inflammatory cytokines such as interleukin-1β (IL-1 β) and tumor necrosis factor-α (TNF-α) from human mast cells (HMC-1) stimulated with phorbol myristate acetate plus calcium ionophore A23187 in a dose-dependent manner. Luteolin also significantly reduced the histamine release from rat peritoneal mast cells stimulated by compound 48/80, a potent histamine liberator. Furthermore, the administration of luteolin markedly inhibited the scratching behavior and vascular permeability induced by pruritogens, such as compound 48/80 or serotonin, in ICR mice. These results suggested that luteolin has potential as a therapeutic agent against inflammation and itch-related skin diseases.

Effect of Electrospun Non-Woven Mats of Dibutyryl Chitin/Poly(Lactic Acid) Blends on Wound Healing in Hairless Mice

The aim of this study was to examine the proliferative ability of dibutyryl chitin (DBC) on scratch wounds in HaCaT keratinocytes and to evaluate the effect of nanoporous non-woven mat (DBCNFM) on skin wound healing in hairless mice using the advantages of DBCNFM, such as high porosity and high surface area to volume. The cell spreading activity of DBC was verified through a cell spreading assay in scratched human HaCaT keratinocytes. Scratch wound experiments showed that DBC notably accelerates the spreading rate of HaCaT keratinocytes in a dose dependent manner. The molecular aspects of the healing process were also investigated by hematoxylin & eosin staining of the healed skin, displaying the degrees of reepithelialization and immunostaining on extracellular matrix synthesis and remodeling of the skin. Topical application of DBCNFM significantly reduced skin wound rank scores and increased the skin remodeling of the wounded hairless mice in a dose dependent way. Furthermore, DBCNFM notably increased the expression of the type 1 collagen and filaggrin. These results demonstrate that DBC efficiently accelerates the proliferation of HaCaT keratinocytes and DBCNFM notably increases extracellular matrix synthesis on remodeling of the skin, and these materials are a good candidate for further evaluation as an effective wound healing agent.

Sulforaphane suppresses TARC/CCL17 and MDC/CCL22 expression through heme oxygenase-1 and NF-κB in human keratinocytes

Sulforaphane (4-methylsulfinylbutyl isothiocyanate, SFN) from broccoli has been used a chemopreventive photochemical as detoxification of xenobiotics and anti-inflammatory, however, there is no studies for Th2 chemokine expression through heme oxygenase-1 and NF-κB in keratinocytes. Atopic dermatitis is a chronically relapsing pruritic inflammatory skin disease. SFN is demonstrated to have anti-inflammatory and anti-oxidant effects. This study aimed to define whether and how SFN regulates Th2-related chemokine production in human HaCaT keratinocytes. The level of chemokine expression was measured by reverse transcription polymerase chain reaction (RT-PCR) and signaling study was performed by Western blot analysis. Chemokine production was determined by enzyme-linked immunosorbent assay. Pretreatment with SFN suppressed interferon-γ (IFN-γ) and tumor necrosis factor (TNF)-α- induced thymus- and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) production in HaCaT keratinocytes. SFN inhibited IFN-γ and TNF-α-induced NF-κB activation as well as STAT1 activation. Interestingly, pretreatment with SFN result in significantly suppressed IFN-γ and TNF-α-induced TARC/CCL17 and MDC/CCL22 production through the induction of HO-1. This suppression was completely abolished by HO-1 siRNA. Furthermore, Carbon monoxide, but not other end products of HO-1 activity, also suppressed IFN-γ and TNF-α-induced TARC/CCL17 and MDC/CCL22 production. These results demonstrate that SFN has an inhibitory role in IFN-γ and TNF-α-induced production of TARC/CCL17 and MDC/CCL22 in human HaCaT cells by inhibition of NF-κB activation and induction of HO-1.

Anti-inflammatory activity of myricetin from Diospyros lotus through suppression of NF-κB and STAT1 activation and Nrf2-mediated HO-1 induction in lipopolysaccharide-stimulated RAW264.7 macrophages

Diospyros lotus is traditionally used for the treatment of diabetes, diarrhea, tumor, and hypertension. The purpose of this study was to investigate the anti-inflammatory effect and underlying molecular mechanisms of myricetin in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Myricetin dose-dependently suppressed the production of pro-inflammatory mediators (NO, iNOS, PGE2, and COX-2) in LPS-stimulated RAW264.7 macrophages. Myricetin administration decreased the production of NO, iNOS, TNF-α, IL-6, and IL-12 in mice. Myricetin decreased NF-κB activation by suppressing the degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Moreover, myricetin attenuated the phosphorylation of STAT1 and the production of IFN-β in LPS-stimulated RAW264.7 macrophages. Furthermore, myricetin induced the expression of HO-1 through Nrf2 translocation. In conclusion, these results suggest that myricetin inhibits the production of pro-inflammatory mediators through the suppression of NF-κB and STAT1 activation and induction of Nrf2-mediated HO-1 expression in LPS-stimulated RAW264.7 macrophages. Graphical abstract This study has elucidated the anti-inflammatory effects of myricetin in in vitro and in vivo.

Inhibitory effect of dibutyryl chitin ester on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 cells

Inflammation is a highly complex process that protects against foreign challenge or tissue injury. The ester derivative dibutyryl chitin (DBC) reportedly accelerates wound healing and exerts an anti-inflammatory effect. However, little is known regarding the inhibitory effect of DBC in anti-inflammation. In this study, we investigated the effect of DBC on the inducible nitric oxide synthetase (iNOS) and cyclooxygenage-2 (COX-2) pathways and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results demonstrate that DBC (MW 3,772) significantly inhibits overproduction of NO and PGE2 as well as pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β, in LPS-stimulated RAW 264.7 macrophages. Inhibition of NO and PGE2 overproduction in LPSstimulated RAW 264.7 macrophages by DBC was mediated through the down-regulation of iNOS and COX-2 expression. These results demonstrate that DBC efficiently inhibits inflammation and has potential as an effective anti-inflammatory and wound healing agent.

Prenylated chalcone from Sophora flavescens suppresses Th2 chemokine expression induced by cytokines via heme oxygenase-1 in human keratinocytes.

We recently reported the inhibitory effect of an oral administration of a Sophora flavescens Aiton methanol extract on the development of atopic dermatitis in the NC/Nga model mice. Heme oxygenase (HO)-1 has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types. The aim of this study was to investigate the possible mechanism by which prenylated chalcone (PC, 7,9,2′,4′-tetrahydroxy-8-isopentenyl-5-methoxychalcone), a natural product isolated from S. flavescens, inhibited cytokine-induced Th2 chemokine expression in human keratinocytes, HaCaT cells. The level of chemokine expression was measured by reverse transcription-polymerase chain reaction and HO-1 study was performed by Western blot analysis. Interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α)-induced thymus- and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), cutaneous T-cell attracting chemokine (CTACK/CCL27) expression in a dose-dependent manner. Interestingly, PC significantly suppressed IFN-γ and TNF-α-induced TARC/CCL17, MDC/CCL22 and CTACK/CCL27 expression via the induction of heme oxygenase (HO)-1. This suppression was completely restored by HO-1 siRNA, suggesting a direct role of HO-1 for the suppressive effect. Furthermore, exogenous CO, but not other end products of HO-1 activity, also suppressed IFN-γ and TNF-α-induced TARC/CCL17, MDC/CCL22 and CTACK/CCL27 expression. These results demonstrate that prenylated chalcone induces HO-1 expression, which in turn HO-1 and/or CO suppresses Th2 chemokine expressions induced by cytokines in human HaCaT cells.

Continentalic acid from Aralia continentalis induces growth inhibition and apoptosis in HepG2 cells

In this study, we investigated the effects of continentalic acid (CA, (−)-pimara-8(14), 15-diene-19-oic acid), a diterpenic acid, isolated from Aralia continentalis, on the proliferation and apoptosis induction of HepG2 cells. In 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the inhibitory effect became gradually stronger with the passage of time, 24, 48 and 72 h after treatment with CA, and the most significant effect was observed at 72 h. CA treatment for 72 h induced DNA fragmentation in a dose-dependent manner. Furthermore, flow cytometric analysis of HepG2 cells exposed to CA showed that apoptotic cells increased in a dose-dependent manner. The induction of apoptosis in HepG2 cells by CA was mediated through the activation of caspase-3, Bak, and Bax, and then through the cleavage of peroxisome proliferator-activated receptor (PARP) and the down-regulation of Bcl-2. These results demonstrate that CA efficiently induces apoptosis and is a good candidate for further evaluation as an effective chemotherapeutic agent.

Protective effects of grape stem extract against UVB-induced damage in C57BL mice skin

Humans have become exposed to another form of a trait which is ultraviolet B (UVB) radiation reaching the earths surface. This has become a major source of oxidative stress that ultimately leads to inflammation, DNA damage, photoaging and pigmentation disorders etc. Although several studies have shown the photo-protective role of different grape parts like the fruits and seeds, little or no data demonstrating the in vivo photo-protective role of grape stem, which is the most discarded part of the grape are available. We evaluated the protective influence of grape stem extract against UVB-induced oxidative damage in C57BL mice characterized by epidermal hyperplasia, pigmentation, collagen degradation and inflammation. Grape stem extract was administered topically 1week before UVB irradiation (120mJ/cm2) and continued until the termination of the experiment. A group of non-irradiated mice and a group of irradiated mice topically administered with propylene were used as a negative and positive control. Epidermal thickness, pigmentation, erythema, mast cell and neutrophil infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were evaluated. Grape stem extract markedly recovered skin damage induced by the UVB radiation through the prevention of epidermal hyperplasia, pigmentation, erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2, Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL mice that grape stem extract reduces UVB-induced oxidative damage and hence can play a protective role in skin photo-damage.

Effects of Antioxidant and Blood Flow Improvement of Grape Leaf Extract and Resveratrol from Vitis romaneti

The purpose of this study is to investigate the effects of 80% ethanol grape leaf extract (VGLE) and resveratrol (VGLR) from Vitis romaneti on antioxidant of red blood cells (RBC) of rat and efficacy of blood flow improvement in a rat model of topical ferric chloride ()-induced carotid artery damage. RBC oxidative hemolysis and plasma lipid peroxidation induced by the aqueous peroxyl radical generator 2,2`-azobis(2-amidinopropane) dihydrochloride were significantly suppressed by VGLE or VGLR in a dose-dependent manner. The treatment seriously damaged the carotid artery: the walls of the artery and blood flow. However, VGLE or VGLR administration has ameliorated the blood flow and suppressed thrombus in blood vessels. These results suggest that VGLE or VGLR ameliorates the oxidative stress of RBC and thrombosis against blood vessel damage.

Effect of Persimmon Leaf Extract on Phthalic Anhydride-induced Allergic Response in Mice.

The purpose of this study was to investigate the anti-allergy activities of persimmon leaf extract (PLE) on a phthalic anhydride (PA)-induced allergic mouse model. A human leukemic mast cell line (HMC-1) was used to examine the inhibitory activity of PLE on the histamine release by human leukemic mast cells. PLE inhibited histamine release from HMC-1 cells in response to cross-linkage of high-affinity IgE receptor-α (FcεRIα). Additionally, a PA-induced allergic mouse model was used to investigate the effects of PLE in vivo. Mice were orally administrated with or without PLE of single dose (250 mg/kg/day) for 31 days. Oral intake of PLE significantly inhibited passive cutaneous reactions. Oral administration of PLE to PA-induced allergic mice also led to a striking suppression of the development of contact dermatitis, ear swelling and lymph node weight. In addition, PA-specific IL-4 production of draining lymph node cells was markedly diminished by PLE oral administration, but not IFN-γ. Furthermore, PLE treatment suppressed PA-induced thymus and activation-regulated chemokine (CCL17) and cutaneous T cell-attracting chemokine (CCL27) expressions in ear tissues. Based on these results, we suggest that PLE may have therapeutic potential as an effective material for management of irritant contact dermatitis or related inflammatory diseases.