Young-Soo Bae

Casuarinin suppresses TARC/CCL17 and MDC/CCL22 production via blockade of NF-κB and STAT1 activation in HaCaT cells

Casuarinin is a naturally occurring tannin that is isolated from the leaves of Hippophae rhamnoides. It has been shown to have anti-oxidant, anti-cancer, anti-viral, and anti-inflammatory activities. The aim of this study was to investigate the possible mechanism by which casuarinin inhibits TNF-α/IFN-γ-induced Th2 chemokines expression in the human keratinocytes cell line HaCaT. We found that casuarinin suppressed TNF-α/IFN-γ-induced expression of TARC and MDC mRNA and protein in HaCaT cells. Casuarinin significantly inhibited TNF-α/IFN-γ-induced activation of NF-κB, STAT1, and p38 MAPK. Furthermore, we observed that p38 MAPK contributes to inhibition of TNF-α/IFN-γ-induced TARC and MDC production by blocking NF-κB and STAT1 activation in HaCaT cells. Taken together, these results suggest that casuarinin may exert anti-inflammatory responses by suppressing TNF-α/IFN-γ-induced expression of TARC and MDC via blockage of p38 MAPK activation and subsequent activation of NF-κB and STAT1. We propose that it could therefore be used as a therapeutic agent against inflammatory skin diseases.

Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-galloyl-β-d-glucose via blockade of NF-κB and STAT1 activation in the HaCaT cells

Keratinocytes, one of major cell types in the skin, can be induced by TNF-alpha and IFN-gamma to express thymus- and activation-regulated chemokine (TARC/CCL17), which is considered to be a pivotal mediator in the inflammatory responses during the development of inflammatory skin diseases, such as atopic dermatitis (AD). In this study, we examined the effect of 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG), isolated from the barks of Juglans mandshurica, on TNF-alpha/IFN-gamma induced CCL17 expression in the human keratinocyte cell line HaCaT. Pretreatment of HaCaT cells with PGG suppressed TNF-alpha/IFN-gamma-induced protein and mRNA expression of CCL17. PGG significantly inhibited TNF-alpha/IFN-gamma-induced NF-kappaB activation as well as STAT1 activation. Furthermore, pretreatment with PGG resulted in significant reduction in expression of CXCL9, 10, and 11 in the HaCaT cells treated with IFN-gamma. These results suggest that PGG may exert anti-inflammatory responses by suppressing TNF-alpha and/or IFN-gamma-induced activation of NF-kappaB and STAT1 in the keratinocytes and might be a useful tool in therapy of skin inflammatory diseases.

Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade of NF-κB and JNK activation in RAW 264.7 macrophages.

We isolated the phenolic glucoside salicortin from a Populus euramericana bark extract, and examined its ability to suppress inflammatory responses as well as the molecular mechanisms underlying these abilities, using lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Salicortin inhibited iNOS expression and the subsequent production of NO in a dose-dependent manner in the LPS-stimulated RAW 264.7 cells. Salicortin significantly suppressed LPS-induced signal cascades of NF-κB activation, such as IKK activation, IκBα phosphorylation and p65 phosphorylation in RAW 264.7 cells. In addition, salicortin inhibited the LPS-induced activation of JNK, but not ERK or p38 MAPK. Furthermore, salicortin significantly inhibited production of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 in the LPS-stimulated RAW 264.7 cells. These findings suggest that salicortin may show its anti-inflammatory activity by suppressing the LPS-induced expression of pro-inflammatory mediators through inhibition of NF-κB and JNK MAPK signaling cascades in macrophages. [BMB Reports 2014; 47(6): 318-323]

Antiinflammatory Effect of the Ethanol Extract of Berberis koreana in a Gerbil Model of Cerebral Ischemia/Reperfusion

Berberis koreana extract (BE) has a strong neuroprotective effect after ischemic stroke in gerbils, which is associated with the inhibition of the N‐methyl‐d‐aspartate receptor. The present study examined the antiinflammatory mechanism of BE after ischemic damage in vitro and in vivo. The BE used contained on average 7.39 ± 0.78 mg/g of berberine. In PC12 cells with inflammation, prostaglandin E2 (PGE2) production was significantly reduced by BE. About 75% of pyramidal cells in the hippocampal CA1 region of gerbils exposed to 5 min of transient ischemia were protected from ischemic damage by BE. Cyclooxygenase‐2 (COX‐2) immunoreactivity and its protein level in the CA1 region of vehicle‐treated animals exposed to an ischemic insult increased with time post‐ischemia, whereas no such changes were observed in BE‐treated animals exposed to ischemia. PGE2 production in BE‐treated ischemic animals was significantly lower than that observed in vehicle‐treated ischemic animals. Summarizing, the potent neuroprotective effect of BE was found to be due to the inhibitions of COX‐2 expression and PGE2 production and its antiinflammatory activity. Copyright

Casuarinin suppresses TNF-α-induced ICAM-1 expression via blockade of NF-κB activation in HaCaT cells.

Hippophae rhamnoides has been extensively used in oriental traditional medicines for treatment of asthma, skin diseases, gastric ulcers, and lung disorders. In this study, we isolated casuarinin from the leaves of H.rhamnoides and examined the effect of casuarinin on the TNF-α-induced ICAM-1 expression in a human keratinocytes cell line HaCaT. Pretreatment with casuarinin inhibited TNF-α-induced protein and mRNA expression of ICAM-1 and subsequent monocyte adhesiveness in HaCaT cells. Casuarinin significantly inhibited TNF-α-induced NF-κB activation. In addition, casuarinin inhibited activation of ERK and p38 MAPK in a dose-dependent manner. Furthermore, pretreatment with casuarinin decreased TNF-α-induced pro-inflammatory mediators, such as IL-1β, IL-6, IL-8, and MCP-1. These results demonstrated that casuarinin exerts its anti-inflammatory activity by suppressing TNF-α-induced expression of ICAM-1 and pro-inflammatory cytokines/chemokines via blockage of activation of NF-κB and ERK/p38 MAPK and can be used as a therapeutic agent against inflammatory skin diseases.

Phenolic compounds in the leaves of Populus ussuriensis and their antioxidant activities.

Two new phenolic glucosides [isograndidentatin A (1) isograndidentatin B (2)], 5 known phenolic glucosides [grandidentatin (3), salireposide (4), populoside (5), populoside A (6), and salicortin (7)], and 2 known phenolic acids [P-coumaric acid (8) and caffeic acid (9)] were isolated from the leaves of Populus ussuriensis. Structure elucidation of 1 and 2 was achieved through extensive spectroscopic techniques. Compounds 1-6 and 9 showed significant antioxidant activities, which were evaluated by the DPPH radical-scavenging method (IC(50) values of 6.68, 6.61, 6.75, 6.84, 6.76, 6.79, and 5.92 microM, respectively) and the ABTS .+ radical-scavenging system (TEAC values of 1.21, 1.28, 1.26, 1.05, 1.69, 1.60, and 2.00 mM, respectively).

Structure elucidation of phenylethanoid glycosides from Paulownia tomentosa Steud. var. tomentosa wood

Paulownia tomentosa Steud. var. tomentosa (Scrophulariaceae), a variety of Paulwownia tomentosa Steud., is a large deciduous tree indigenous in China and widely distributed in Eastern Asia; it is usually 10–20 m tall, with strong branches. It blooms in May and June, before the leaves appear. The flowers are white to light purple in color. The fruit is a double-capsuled, red-brown ligneous seed ball, approximately 4 cm long. The fruit ripens in autumn and after bursting many winged seeds are set free. The leaves of the variety are densely hairy, which distinguishes it from the sparse haired leaves of Paulwownia tomentosa Steud. (Hong et al. 1998; Smejkal et al. 2007). In traditional medicine, the bark, wood, fruit and leaf of the plant are used to treat cough, bronchitis, hemorrhoid, asthma, high blood pressure and bacterial diarrhea (Jiang 2003). Chemical constituents of P. tomentosa Steud. var. tomentosa have never been reported, to date, though its medicinal properties are well known. From the Paulownia species, several classes of characteristic secondary metabolites have been isolated, including lapachol type naphthoquinones (Huang et al. 2004), phenylpropanoid glycosides (Ota et al. 1993; Kang et al. 1994), iridoids (Damtoft and Jensen 1993) and lignans (Takahash and Nakagawa 1966; Ayres and Loike 1990; Okazaki et al. 1997; Huang et al. 2004; Silvestre et al. 2005). In our previous paper concerning the aqueous acetone extract of the Paulownia coreana inner bark, we identified three epimeric phenylpropanoid glycosides, cistanoside F, campneoside II and isocampneoside II (Kim et al. 2007). This work is a report on the purification and elucidation of a novel phenylethanoid glycoside (4), together with three that are known: verbascoside (1), isoverbascoside (2) and campneoside I (3).

Phenylpropanoid glycosides from the leaves of Paul o wnia coreana

Study on the water soluble fraction from the leaves of Paulownia coreana led to the isolation of verbascoside (1), isoverbascoside (2), campneoside II (3), and a new phenylpropanoid glycoside, (R,S)-7-hydroxy-7-(3,4-dihydroxyphenyl)-ethyl-O-α-L-rhamnopyranosyl(1 → 3)-β-d-(6-O-caffeoyl)-glucopyranoside (4). The structures of these compounds were established on the basis of spectroscopic evidence.

Studies on the phenylethanoid glycosides with anti-complement activity from Paulownia tomentosa var. tomentosa wood.

Four epimeric phenylethanoid glycosides, including a new one, R,S-β-ethoxy-β-(3,4-dihydroxyphenyl)-ethyl-O-α-l-rhamnopyranosyl(1 → 3)-β-d-(6-O-E-caffeoyl)-glucopyranoside named isoilicifolioside A (1), and three known compounds, ilicifolioside A (2), campneoside II (3), and isocampneoside II (4), were isolated from Paulownia tomentosa var. tomentosa wood. The structures of the four compounds were elucidated by the interpretation of 1D and 2D NMR and MS spectra. This is the first report of the chemical profile of this tree. Compounds 1–4 exhibited excellent anti-complement activity with IC50 values less than 74 μM, compared with tiliroside (IC50 = 104 μM) and rosmarinic acid (IC50 = 182 μM) that were used as positive controls.

Chemical constituents from the stem bark of Acer barbinerve

0009-3130/11/4704-0636 2011 Springer Science+Business Media, Inc. Department of Forest Biomaterials Engineering, College of Forest Environmental Sciences, Kangwon National University, Chuncheon 200701, Republic of Korea, fax: 82 33 256 8320, e-mail: bae@kangwon.ac.kr. Published in Khimiya Prirodnykh Soedinenii, No. 4, pp. 560–561, July–August, 2011. Original article submitted April 27, 2010. Chemistry of Natural Compounds, Vol. 47, No. 4, September, 2011 [Russian original No. 4, July–August, 2011]