Oh Wook Kwon

Bioactive Lignans from the Trunk of Abies holophylla

Six new lignans (1-6) were isolated from the trunk of Abies holophylla MAXIM, together with 11 known lignans (7-17). The structures of 1-7 were elucidated by spectroscopic methods, acid hydrolysis, and use of the modified Moshers method. The effects of the isolates on nerve growth factor induction in a C6 rat glioma cell line were evaluated. Compounds 6, 7, and 13 showed significant induction of nerve growth factor secretion at concentrations of 10 μM. Compounds 1, 5, 6, and 16 showed moderate inhibitory effects on nitric oxide production in lipopolysaccharide-activated BV-2 cells (IC50 28.5-36.4 μM).

Phenolic derivatives from the rhizomes of Dioscorea nipponica and their anti-neuroinflammatory and neuroprotective activities.

ETHNOPHARMACOLOGICAL RELEVANCE Dioscorea nipponica (Dioscoreaceae) have been used as traditional medicines for diabetes, inflammatory and neurodegenerative diseases in Korea. The aim of the study was to isolate the bioactive components from the rhizomes of Dioscorea nipponica and to evaluate their anti-neuroinfalmmatory and neuroprotective activities. MATERIAL AND METHODS The phytochemical investigation of 50% EtOH extract of Dioscorea nipponica using successive column chromatography over silica gel, Sephadex LH-20, and preparative high performance liquid chromatography (HPLC) resulted in the isolation and identification of 17 phenolic derivatives, including four new phenolic compounds (1-4). The structural elucidation of these compounds was based on spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy techniques, mass spectrometry, and optical rotation. All isolated compounds were evaluated for their effects on nerve growth factor (NGF) secretion in a C6 rat glioma cell line and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 cells. The neurite outgrowth of compound 16 was further evaluated by using mouse neuroblastoma N2a cell lines. RESULTS Three new stilbene derivatives, diosniponol C (1), D (2) and diosniposide A (3) and one new phenanthrene glycoside, diosniposide B (4), together with 13 known compounds were isolated from the rhizomes of Dioscorea nipponica. Of the tested compounds (1-17), phenanthrene, 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene (16) was the most potent NGF inducer, with 162.35±16.18% stimulation, and strongly reduced NO levels with an IC50 value of 19.56 μM in BV2 microglial cells. Also, it significantly increased neurite outgrowth in N2a cells. CONCLUSIONS This study supports the ethnopharmacological use of Dioscorea nipponica rhizomes as traditional medicine.

Anti-neuroinflammatory diarylheptanoids from the rhizomes of Dioscorea nipponica

In a continuing search for bioactive constituents from Dioscoreaceae medicinal plants, two new cyclic diarylheptanoids, diosniponol A (1) and B (2), together with 10 known compounds (3-12) were isolated from the rhizomes of Dioscorea nipponica. The structures of these new compounds were determined by spectroscopic analyses, including extensive two-dimensional nuclear magnetic resonance, high-resolution mass spectrometry, and optical rotation. All isolated compounds 1-12 were evaluated for their effects on nitric oxide (NO) production in murine microglia cell line BV-2. Compounds 8 and 11 showed potent inhibitory activities on NO production (IC50 13.36 and 14.36 μM, respectively) without cell toxicity in lipopolysaccharide-activated BV-2 cells.

A substituted 3,4-dihydropyrimidinone derivative (compound D22) prevents inflammation mediated neurotoxicity; role in microglial activation in BV-2 cells

A novel synthetic 3,4-dihydropyrimidinone derivative, compound D22 (ethyl 6-methyl-4-(3-phenoxyphenyl)-2-thioxo-3,4-dihydropyrimidine-5-carboxylate), was found to exert anti-inflammatory properties in lipopolysaccharide-stimulated microglial BV-2 cells. Compound D22 reduced the pro-inflammatory factors such as nitric oxide, prostaglandin E(2), tumor necrosis factor-α and interleukin-1β. Moreover, it suppressed the expressions of inducible NO synthase and cyclooxygenase-2. Compound D22 inhibited the activation of mitogen-activated protein kinases. When compound D22-conditioned media from BV-2 cells were applied to N2a cells, neuronal cell death was inhibited via suppression of caspase-3 activation and regulation of Bcl-2 and Bax proteins expression. These results suggest that compound D22 may be useful for treating neurodegenerative diseases related with neuroinflammation.

Five New Oxylipins from Chaenomeles sinensis

In the course of our continuing search for bioactive constituents of Korean medicinal plants, we isolated five new oxylipins, chaenomic acid A–E (1–5), and six known ones (6–11) from the twigs of Chaenomeles sinensis. The structures of the new compounds (1–5) were determined by spectroscopic methods, including 1D and 2D NMR (1H and 13C NMR, 1H–1H COSY, HMQC, HMBC, and NOESY), olefin cross-metathesis, and LC/MS analysis. The known compounds (6–11) were identified by comparison of their spectroscopic data and specific optical rotation with the reported data. The isolated compounds (1–11) were tested for their inhibitory effects on nitric oxide production in lipopolysaccharide-activated murine microglial cells and for their cytotoxic activities against four human cancer cell lines (A549, SK-OV-3, A498, and HCT-15).

Metabolite profiling of enzymatically hydrolyzed and fermented forms of Opuntia ficus-indica and their effect on UVB-induced skin photoaging.

Fermentation of natural products is emerging as an important processing method and is attracting a lot of attention because it may have the advantage of having a new biological function. In this study, fruits of Opuntia ficus-indica were enzymatically hydrolyzed and then fermented with two species of yeast. We identified novel prominent markers in enzymatically hydrolyzed O. ficus-indica (EO) and fermented O. ficus-indica (FO) samples by using an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. We also evaluated the effect of EO and FO on photoaging of skin cells exposed to ultraviolet radiation. We identified the major fermented metabolite in the FO as ferulic acid. Our in vitro study indicated that FO significantly enhanced the concentration of pro-collagen type 1 than the EO, by increasing the TGF-β1 production.

A NEW CYCLIC TRITERPENE SAPONIN FROM PHYTEUMA JAPONICUM

A new cyclic triterpene saponin, phyteujaposide (1) and eight known compounds (2-9) were isolated from the leaves of Phyteuma japonicum. The structure of the new compound (1) was elucidated by 1D and 2D data analysis, acid hydrolysis and GC-MS. Compounds 7 and 9 potently inhibited the NO production in LPS-activated BV-2 cells and compounds 5 and 6 showed a significant secretion induction of NGF in C6 glioma without cell toxicity. Phyteuma japonicum Miquel (Campanulaceae), commonly known as horned rampion, is a perennial herb widely distributed throughout Korea, China, and Japan. The young leaves of this plant are as a salad raw consumed in Korea and many plant of Campanulaceae family were used as an herbal drug to treat bronchitis, inflammation, asthma, pulmonary tuberculosis, and ear-pains. In previous phytochemical studies, phenolic compounds, flavonoids and triterpene saponins were isolated from Phyteuma genus, and some of them showed antioxidant activity. However, no phytochemical and biological investigations have been reported on the secondary metabolites of this species. The medicinal importance of the species and the lack of information with regards to its chemical constituents prompted this investigation of constituents of the leaves of P. japonicum. In our screening test, the MeOH extract of P. japonicum exhibited inhibitory activity for the nitric oxide (NO) production HETEROCYCLES, Vol. 89, No. 8, 2014 1913

A fermented barley and soybean formula enhances skin hydration.

Skin hydration is one of the primary aims of beauty and anti-aging treatments. Barley (Hordeum vulgare) and soybean (Glycine max) are major food crops, but can also be used as ingredients for the maintenance of skin health. We developed a natural product-based skin treatment using a barley and soybean formula (BS) incorporating yeast fermentation, and evaluated its skin hydration effects as a dietary supplement in a clinical study. Participants ingested a placebo- (n = 33) or BS- (3 g/day) containing drink (n = 32) for 8 weeks. A significant increase in hydration in the BS group as compared to the placebo group was observed on the faces of subjects after 4 and 8 weeks, and on the forearm after 4 weeks. Decreases in stratum corneum (SC) thickness were also observed on the face and forearm. BS enhanced hyaluronan (HA) and skin barrier function in vitro and reduced Hyal2 expression in human dermal fibroblasts (HDF). BS also recovered ultraviolet (UV) B-induced downregulation of HA in HaCaT cells. These results suggest that BS has promising potential for development as a health functional food to enhance skin health.

Dietary supplementation with a fermented barley and soybean mixture attenuates UVB-induced skin aging and dehydration in hairless mouse skin

This study evaluated the protective effects of dietary supplementation with a fermented barley and soybean mixture (BS) on ultraviolet (UV) B-induced photoaging in hairless mice. Skin aging-related parameters and protein levels related to skin wrinkles and moisturization in mice were analyzed. The BS reduced wrinkle formation, skin thickening, transepidermal water loss, and matrix metalloproteinases-1 expression in skin. Skin hydration and pH were increased in the BS group. BS attenuated filaggrin expression as well as free amino acid and glycerol production. BS increased superoxide dismutase activity as well as increased expression of nuclear factor (erythroid-derived 2)-like 2, procollagen type-I, and decreased erythema. These results suggest that BS protects against photoaging induced by UVB in vivo, indicating the potential of such mixtures as anti-photoaging dietary supplementation.