Jum Soon Kang

Identification of a novel compound that inhibits iNOS and COX-2 expression in LPS-stimulated macrophages from Schisandra chinensis.

A novel alpha-iso-cubebenol, which has anti-inflammatory effects in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, was isolated from the fruits of Schisandra chinensis. alpha-iso-cubebenolinhibited LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production. Consistent with these findings, alpha-iso-cubebenol also reduced the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at the protein and mRNA levels in a concentration-dependent manner. alpha-iso-cubebenol also inhibited LPS-induced nuclear translocation of the NF-kappaB p65 subunit. Furthermore, alpha-iso-cubebenol suppressed the phosphorylation of ERK, JNK, and p38 kinase induced by LPS. Since the novel alpha-iso-cubebenol blocked the production of several pro-inflammatory mediators induced by LPS in macrophages, the molecule can be useful material for the development of anti-inflammatory agents against bacterial infections or endotoxin.

Therapeutic effects of α-iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, against sepsis

α-Iso-cubebenol, a natural compound isolated from the Schisandra chinensis fruit, strongly enhances survival rate in cecal ligation and puncture (CLP) challenge-induced sepsis. Mechanistically, α-iso-cubebenol markedly reduces viable bacteria in the peritoneal fluid and peripheral blood, by increasing production of superoxide anion. α-Iso-cubebenol also significantly attenuates widespread immune cell apoptosis in a mouse CLP sepsis model, and inhibits the production of proinflammatory cytokines including interleukin-1β (IL-1β) and IL-6 in CLP mice and lipopolysaccharide-stimulated splenocytes. Taken together, the results indicate that α-iso-cubebenol can reverse the progression of septic shock by triggering multiple protective downstream signaling pathways to enhance microbial killing and maintain organ function and leukocyte survival.

Changes in Cordycepin and Liquiritigenin Content and Inhibitory Effect on NO Production in Fermented Licorice and Dongchunghacho

Traditional Korean fermented herbal plants are potential sources of new food that promote health, but they are still produced by yeast, fungi or bacteria fermentation. In the present work, mushroom (Paecilomyces tenuipes and Cordyceps militaris) fungal dongchunghacho were used to fermented Glycyrrhiza uralensis Fischer (licorice) or mixed with pupa. The pupa were tested as solid substrates for the production of corcycepin, liquiritin, and liquiritigenin. The fermented substrates were analyzed the content of cordycepin, liquiritin, liquiritigenin, and glycirrhizin productivity and inhibitory activity of NO. The cordycepin content of 70% EtOH extract from the fermented mixture of licorice and 50% pupa with C. militaris increased maximum at 33 times. Pupa was very excellent for the production of cordycepin. The liquiritin content was decreased in all the assays inoculated with P. tenuipes and C. militaris dongchunghachos. The liquiritigenin content was higher when fermented with P. tenuipes than C. militaris. The addition of pupa significantly reduced the liquiritin content and glycyrrhizin production. As a result, the liquiritigenin content increased in fermented P. tenuipes and C. militaris, and liquiritin and glycyrrhizin decreased. The inhibition of NO production in the different ethanolic extracts fermented with licorice and pupa was also significantly increased and higher than that of a nonfermented extract in higher polar solvent extracts. The contents of cordycepin and biological active compounds were altered in accordance with the concentration of pupa and fungi. This study provides basic data for use in developing dongchunghacho fungi as a functional food resource.

Anti-metastatic Effect of Garlic Hexane Extract on Lung Metastasis Induced by Melanoma B16F10 Cells in Mice

Metastatic cancer is one of the main causes of cancer-related death since they rarely respond to available treatments. There is epidemiologic evidence that high garlic consumption decreases the incidence of cancer. Recent studies of our laboratory have revealed that a garlic-extracts is effective in suppressing metastasis. For experimental metastasis, C57BL/6 mice were injected intravenously with melanoma B16F10 cells in the tail vein, and were orally administered various concentrations (0, 50, 100 or 200 mg/kg body weight) of garlic hexane extract (GHE) for 21 days. The incidence and the area of the melanoma cell colony occupied by the poorly differentiated carcinoma were significantly lower in dose-dependent in 50, 100 and 200 mg/kg BW GHE–treated mice compared with control mice. In conclusion, the results of the present study show that GHE administration prevents lung metastasis in C57BL/6 mice.

Isolation, Quality Evaluation, and Seasonal Changes of Bakkenolide B in Petasites japonicus by HPLC

The leaves of Peatasites japonicus are a traditional oriental medicine with diverse biological activities. A simple and specific analytical method for the quantitative determination of bakkenolide B constituents from methanolic extract of the leaves of P. japonicus was developed. Bakkenolide B was isolated from the leaves of P. japonicus, and its structure was elucidated based on 1D, 2D NMR, and GC-MS spectral data. A liquid chromatographic method was developed to evaluate the quality of P. japonicus through determination of major active compound, bakkenolide B. The wavelengths at 254 and 215 nm were chosen to determine bakkenolide B. The recovery of the method was in the range of 98.6 to 103.1%, and bakkenolide B showed good linearity (r 2 =0.999) within test ranges. The developed method was applied to the determination of bakkenolide B in the plant part and seasonal changes. The results showed that the content of bakkenolide B in the leaf was higher than in the petiole and rhizome. In this study, a simple, rapid, and reliable high-performance liquid chromatography method was used to determine the percentage and composition of bakkenolide B in P. japonicus procured from different Petasites species plants in South Korea. The method can be employed in routine quantitative analysis and quality control of different products in the market.

Heme Oxygenase-1-mediated Anti-inflammatory Effect of a Novel Garlic Compound in RAW264.7 Murine Macrophages

This study investigated the effects of (10Z)-1-[(5Z,8Z)-tetradeca-5,8-dienoyloxy]-3-[(Z)-tetradec-8-enoyloxy]propan-2-yl hexadec-10-enoate (TTPH) from garlic on the inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2) systems in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The TTPH dose-dependently reduced nitrite accumulation and production of prostaglandin E2 in the supernatants of LPS-stimulated macrophages. Markedly reduced iNOS and COX-2 enzyme activities were observed in Western blots. In addition, a dose-dependent change in mRNA expression was recorded using reverse transcription-polymerase chain reaction analyses. Moreover, TTPH exerted antiinflammatory activity by inducing heme oxygenase-1 (HO-1) expression; this was supported by the use of the HO-1 inhibitor protoporphyrin IX, which abolished the inhibitory effect of TTPH on the production of nitric oxide, tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-6 in LPS-stimulated macrophages. These observations indicate that TTPH inhibits the expression of iNOS and COX-2, and up-regulates HO-1 in activated macrophages. The possible link of this effect to the beneficial features attributed to garlic is discussed.