Kwan Hee Park

Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E2 (COX-2) production of flavonoids from seeds of Prunus tomentosa Thunberg.

Chemical investigation of the 80% Me2CO extract from the seeds of Prunus tomentosa led to the isolation and identification of six flavonoids: kaempferol (1), kaempferol 3-O-α-L-rhamnopyranoside (2; afzelin), kaempferol 3-O-β-D-(6-acetyl)-glucopyranosyl(1→4)-α-L-rhamnopyranoside (3; multiflorin A), kaempferol 3-O-β-D-glucopyranosyl(1→4)-α-L-rhamnopyranoside (4; multiflorin B), quercetin 3-O-α-L-rhamnopyranoside (5; quercitrin), and quercetin 3-O-β-D-glucopyranosyl (1→4)-α-L-rhamnopyranoside (6; multinoside A). Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E2 production in interferon-γ (INF-γ) and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro (COX-2) of the isolated compounds were evaluated. Compounds 1, 5, and 6 exhibited potent anti-oxidative activity in the DPPH radical scavenging assay with IC50 values of 57.2, 59.4, and 54.3 μg/mL respectively. The positive control, ascorbic acid, had an IC50 of 55.5 μg/mL. Compounds 1, 5, and 6 also reduced COX-2 levels in a dose dependent manner with IC50 values of 10.2, 8.7, and 9.6 μg/mL respectively, with the positive control, indomethacin, having an IC50 of 5.1 μg/mL. All six compounds inhibited NO production in a dose dependent manner with IC50 values of 35.1, 42.8, 40.0, 44.8, 43.7, and 43.9 μg/mL respectively, while the positive control, L-NMMA, had an IC50 of 42.1 μg/mL.

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-β-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.

Pep-1 peptide-conjugated elastic liposomal formulation of taxifolin glycoside for the treatment of atopic dermatitis in NC/Nga mice.

In order to develop topical preparations of taxifolin glycoside (TXG) for the treatment of atopic dermatitis (AD), formulations of Pep-1 peptide-conjugated elastic liposomes (Pep1-EL) were examined for their in vitro skin permeation profile and in vivo therapeutic efficacy. TXG-loaded Pep1-EL - a nanovesicle consisting of phosphatidylcholine, Tween 80, N-[4-(p-maleimidophenyl)butyryl]-phosphatidylethanolamine (MPB-PE), and Pep-1 peptide - is 130nm in size, and has a zeta potential of 25mV and a deformability index value of 60. Here, we examined the skin permeability of several topical preparations using a Franz diffusion cell mounted with depilated mouse skin and found that formulations of Pep1-EL exhibited superior absorption when compared to aqueous solution, EL or Pep-1 peptide-admixed EL formulations. Both transepidermal water loss and skin surface hydration were also measured using AD-induced NC/Nga mice, and the TXG-loaded Pep1-EL treatment group displayed a significantly expedited recovery in skin barrier function when compared to the controls treated with a TXG aqueous solution (p<0.05). AD-associated immune responses - including serum interleukine-4, immunoglobulin E, and interferon-gamma - were also regulated by topical application of TXG-loaded Pep1-EL. In conclusion, the novel Pep1-EL formulation of TXG shows substantial promise in the treatment of AD as a result of its desirable skin delivery-promoting capability.

Effect of taxifolin glycoside on atopic dermatitis-like skin lesions in NC/Nga mice

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‐β‐D‐glucopyranoside (TAX) from the roots of Rhododendron mucronulatum (RM) was examined to determine whether its immunomodulatory effect was applicable for treating atopic dermatitis.

Inhibitory effects of phenolic compounds from needles of Pinus densiflora on nitric oxide and PGE2 production

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 E4 (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 E2 production in IFN-γ- and lipopolysaccharide-stimulated RAW 264.7 cells were examined.

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.

Atopic Dermatitis-Like Skin Lesions Reduced by Topical Application and Intraperitoneal Injection of Hirsutenone in NC/Nga Mice

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.

Inhibition of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Expression by Phenolic Compounds from Roots of Rhododendron mucronulatum

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

Quercetin-3-O-(2″-galloyl)-α-l-rhamnopyranoside inhibits TNF-α-activated NF-κB-induced inflammatory mediator production by suppressing ERK activation.

Quercetin and its derivatives have anti-inflammatory and anti-oxidant effects. However, the effect of quercetin-3-O-(2″-galloyl)-α-l-rhamnopyranoside (QGR), a new quercetin derivative, on the tumor necrosis factor (TNF)-α-stimulated production of inflammatory mediators in keratinocytes is unclear. In addition, the effect of QGR on the ERK and NF-κB-mediated inflammatory process has not been studied. In human keratinocyte HaCat cells, we investigated the effect of QGR on the TNF-α-stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-κB, which regulates the transcription genes involved in immune and inflammatory responses. QGR inhibited the TNF-α-stimulated production of cytokines and chemokines in HaCaT cells. QGR, dexamethasone, cyclosporine A, Bay 11-7085 (an inhibitor of NF-κB activation) and cell signaling ERK inhibitor attenuated the TNF-α-induced formation of inflammatory mediators and activation of the NF-κB and ERK. Unlike other compounds, dexamethasone and cyclosporine A did not reduce formation of reactive oxygen species. The results show that QGR may attenuate TNF-α-stimulated inflammatory mediator production in HaCaT cells by suppressing the activation of the ERK-mediated NF-κB pathway that is mediated by reactive oxygen species. Additionally, QGR may exhibit a preventive effect against the proinflammatory mediator-induced skin diseases by inhibiting the activation of the ERK and NF-κB pathways.

Effect of topical application of quercetin-3-O-(2″-gallate)-α-l-rhamnopyranoside on atopic dermatitis in NC/Nga mice.

BACKGROUND Quercetin-3-O-(2″-gallate)-α-l-rhamnopyranoside (QGR) is a new quercetin derivative which is isolated from the leaves of Acer ginnala Maxim, a native plant of Korea. Quercetin has several biological effects including antioxidative, anti-inflammatory, and anti-allergic effects. However, the topical effect of QGR on atopic dermatitis (AD) like skin lesion in NC/Nga mice has not been studied. OBJECTIVE To evaluate the anti-inflammatory and anti-allergic effect of QGR in a murine model of atopic dermatitis. METHODS We measured inducible nitric oxide synthase (iNOS) and cyclooxygenase -2(COX-2) level in RAW264.7 cell with QGR treatment. And after induction of AD like skin lesions with Dermatophagoides farina (Df) ointment, mice were treated with QGR and control drugs. Clinical scores, interleukin (IL) 4, 5, and 13, serum IgE, eosinophil levels, iNOS and COX-2 level were evaluated. RESULTS Results show that mRNA level of iNOS and COX-2 in vitro were decreased after QGR treatment. Topical QGR markedly decreased the iNOS and COX-2 mRNA expressions in the skin. QGR also significantly suppressed the increase in the level of total plasma IgE and eosinophils. In addition, topical application of QGR down-regulated the expressions of the cytokines, IL-4,5 and 13, which were induced by Df ointment stimulation. CONCLUSIONS In the present study, we showed that topical application of QGR ameliorated Df-induced AD-like inflammatory responses in NC/Nga mice. These results demonstrate that QGR might be beneficial in the treatment of AD.