Myun-Ho Bang

Flavonol glycosides from the aerial parts of Aceriphyllum rossii and their antioxidant activities.

The methanol extract obtained from the aerial parts ofAceriphyllum rossii (Saxifragaceae) was fractionated into ethyl acetate (EtOAc),n-BuOH and H2O layers through solvent fractionation. Repeated silica gel column chromatography of EtOAc andn-BuOH layers afforded six flavonol glycosides. They were identified as kaempferol 3-O-β-D-glucopyranoside (astragalin,1), quercetin 3-O-β-D-glucopyranoside (isoquercitrin,2), kaempferol 3-O-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside (3), quercetin 3-O-α-L-rhamnopyranosyl (1→6)-β-D-glucopyrano-side (rutin,4), kaempferol 3-O-[α-L-rhamnopyranosyl (1→4)-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside] (5) and quercetin 3-O-[α-L-rhamnopyranosyl (1→4)-α-L-rhamnopyranosyl (1→6)-β-D-glucopyranoside] (6) on the basis of several spectral data. The antioxidant activity of the six compounds was investigated using two free radicals such as the ABTS free radical and superoxide anion radical. Compound1 exhibited the highest antioxidant activity in the ABTS2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging method. 100 mg/L of compound1 was equivalent to 72.1±1.4 mg/L of vitamin C, and those of compounds3 and5 were equivalent to 62.7±0.5 mg/L and 54.3±1.3 mg/L of vitamin C, respectively. And in the superoxide anion radical scavenging method, compound5 exhibited the highest activity with an IC50 value of 17.6 ± 0.3 μM. In addition, some physical and spectral data of the flavonoids were confirmed.

In Vitro Antioxidant and Anti-inflammatory Activities of Jaceosidin from Artemisia princeps Pampanini cv. Sajabal

Oxidized low-density lipoprotein (oxLDL) plays a key role in the inflammatory processes of atherosclerosis. Jaceosidin isolated from the methanolic extracts of the aerial parts of Artemisia princeps Pampanini cv. Sajabal was tested for antioxidant and anti-inflammatory activities. Jaceosidin inhibited the Cu2+-mediated LDL oxidation with IC50 values of 10.2 μM in the thiobarbituric acid-reactive substances (TBARS) assay as well as the macrophage-mediated LDL oxidation. The antioxidant activities of jaceosidin were exhibited in the conjugated diene production, relative electrophoretic mobility, and apoB-100 fragmentation on copper-mediated LDL oxidation. Jaceosidin also inhibited the generation of reactive oxygen species (ROS) concerning in regulation of NF-κB signaling. And jaceosidin inhibited nuclear factor-kappa B (NF-κB) activity, nitric oxide (NO) production, and suppressed expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.

Fucosterol isolated from Undaria pinnatifida inhibits lipopolysaccharide-induced production of nitric oxide and pro-inflammatory cytokines via the inactivation of nuclear factor-κB and p38 mitogen-activated protein kinase in RAW264.7 macrophages.

It has been reported that fucosterol has anti-diabetic, anti-oxidant, and anti-osteoporotic effects. We investigated the anti-inflammatory effects and the underlying molecular mechanism of fucosterol in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Fucosterol suppressed the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) by downregulating their transcriptions, and subsequently inhibited the productions of nitric oxide, TNF-α, and IL-6. In addition, fucosterol attenuated LPS-induced DNA binding and the transcriptional activity of nuclear factor-κB (NF-κB). These reductions were accompanied by parallel reductions in the phosphorylation and nuclear translocation of NF-κB. Furthermore, fucosterol attenuated the phosphorylations of mitogen-activated protein kinase kinases 3/6 (MKK3/6) and mitogen-activated protein kinase-activated protein kinase 2 (MK2), which are both involved in the p38 MAPK pathway. These results suggest that the anti-inflammatory effects of fucosterol are associated with the suppression of the NF-κB and p38 MAPK pathways.

Lignans from the fruits of cornus kousa burg. and their cytotoxic effects on human cancer cell lines

The fruits of Cornus kousa Burg. were extracted with 80% aqueous MeOH, and the concentrated extract partitioned with EtOAc, n-BuOH and H2O. Six lignans were isolated from the EtOAc fraction through repeated silica gel, ODS and Sephadex LH-20 column chromatographies. From the physico-chemical data, including NMR, MS and IR, the chemical structures of the compounds were determined to be (+)-pinoresinol (1), (-)-balanophonin (2), (+)-laricresinol (3), erythro-guaiacylglycerol-β-coniferyl aldehyde ether (4), threo-guaiacylglycerol-β-coniferyl aldehyde ether (5) and dihydrodehydrodiconiferyl alcohol (6), which were isolated for the first time from this plant. Most of these compounds showed cytotoxicity against human colon carcinoma (HCT-116) and human hepatocellular carcinoma (HepG2) cell lines in vitro, with IC50 values ranging from 19.1 to 71.3 μg/mL.

Stewartia koreana extract stimulates proliferation and migration of human endothelial cells and induces neovasculization in vivo

Angiogenesis, the growth of new blood vessels from preexisting vasculature, plays an important role in physiological and pathological processes such as embryonic development and wound healing. This study investigated the effects of methanol extracts of Stewartia koreana leaves (SKE) on angiogenesis. Stewartia koreana significantly promoted the proliferation and migration of human umbilical vein endothelial cells in a dose‐dependent manner. The SKE induced endothelial cell proliferation in the range of 50 µg/mL without cytotoxicity. Treatment of HUVECs resulted in the activation of the mitogen‐activated protein kinases that was correlated with endothelial cell proliferation and migration. SKE also stimulated angiogenesis in a chick chorioallantoic membrane assay, demonstrating promotion of new blood vessel formation in vivo. Local administration of SKE onto skin punched wounds resulted in increased von Willebrand Factor antigen, indicating that it stimulated neovasculization in the wound region. The results suggest that Stewartia koreana extracts may potentially be useful for the development of agents to accelerate vascular wound healing or to promote the growth of collateral blood vessels in ischemic tissues. Copyright

Inhibitory effects of a spinasterol glycoside on lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines via down-regulating MAP kinase pathways and NF-κB activation in RAW264.7 macrophage cells.

Extracts from the leaves of Stewartia koreana are known to exhibit strong anti-inflammatory activity. Investigation of bioactive compounds from S. koreana has led to the isolation of 3-O-β-d-glucopyanosylspinasterol (spinasterol-Glc), a spinasterol glycoside. In the present study, we examined the effects of spinasterol-Glc on production of nitric oxide (NO) and proinflammatory cytokines in LPS-treated RAW264.7 macrophage cells and in mouse models. Our results showed that spinasterol-Glc inhibited the production of NO and proinflammatory cytokines such as TNF-α, IL-6 and IL-1β in dose-dependent manners in LPS-treated RAW264.7 cells. Spinasterol-Glc inhibited the expression of iNOS and the proinflammatory cytokine genes. Spinasterol-Glc also inhibited phosphorylation of IκB-α and IKKα/β as well as translocation of NF-κB to the nucleus. We demonstrated that spinasterol-Glc reduced transcription of the NF-κB minimal promoter and NF-κB DNA binding activity. Administration of the spinasterol-Glc significantly decreased the plasma levels of these inflammatory mediators including TNF-α, IL-6 and IL-1β in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results suggest that spinasterol-Glc has effective inhibitory effects on production of inflammatory mediators via inhibition of MAP kinases/NF-κB activities, and can be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.

Lignans from the flowers of Osmanthus fragrans var. aurantiacus and their inhibition effect on NO production

A new lignan, (7R,7′R,8R,8′R)-8-hydroxypinoresinol 8-O-β-D-glucopyranoside 4′-methyl ether (7), was isolated from the flowers of Osmanthus fragrans var. aurantiacus along with six known lignans: (+)-phillygenin (1), phillyrin (2), (−)-phillygenin (3), (−)-epipinoresinol-β-D-glucoside (4), taxiresinol (5), and (−)-olivil (6). The structure of the new compound was elucidated on the basis of 1D- and 2D-NMR spectroscopic analysis and specific rotation data. The compounds isolated from the flowers of O. fragrans var. aurantiacus were evaluated for inhibitory activities on nitric oxide production in lipopolysaccharide-stimulated macrophage RAW 264.7 cells. (+)-Phillygenin (1), phillyrin (2), and (−)-phillygenin (3) exerted the strongest inhibitory activities on NO production with IC50 values of 25.5, 18.9, and 25.5 μM, respectively. These compounds may prove beneficial in the development of natural agents for prevention and treatment of inflammatory diseases.

Isolation of megastigmane sesquiterpenes from the silkworm (Bombyx mori L.) droppings and their promotion activity on HO-1 and SIRT1

The silkworm (Bombyx mori L.) droppings were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned in succession with EtOAc, n-BuOH, and H2O. From the EtOAc fraction, five megastigmane sesquiterpenes were isolated through repeated silica gel and ODS column chromatography. According to the results of spectroscopic data, such as NMR, MS, and IR, the chemical structures of the isolated compounds were determined as (3S,5R,8R)-3,5-dihydroxymegastigma-6,7-dien-9-one (1), (S)-dehydrovomifoliol (2), (6R,7E,9R) -9-hydroxy-4,7-megastigmadien-3-one (3), (3S,5R,6S,7E)-3,5,6-trihydroxy-7-megastigmen-9-one (4), (6R,9R)-9-hydroxy-4-megastigmen-3-one (5). Compounds 2 through 5 were isolated for the first time from silkworm droppings. GC/MS analysis indicated silkworm powder contained compound 3, and mulberry leaves contained compound 4. Compounds 1 and 5 increased the expression of heme oxygenase-1 and SIRT1 in HepG2 and HEK239 cells, respectively. Heme oxygenase-1 is considered to be an antioxidant enzyme that catabolizes heme to carbon monoxide, free iron and biliverdin, while SIRT1 is the mammalian homologue of the yeast silent information regulator (Sir)-2, which are involved in the suppression of inflammatory mediators or factors that may be used to improve atopy-related symptoms.

Cytotoxic and ACAT-inhibitory sesquiterpene lactones from the root ofIxeris dentata formaalbiflora

Ixeris dentata formaalbiflora was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc,n-BuOH and H2O. Eight sesquiterpenes were isolated through repeated silica gel and octadecyl silica gel (C18, ODS) column chromatography of the EtOAc andn-BuOH fractions. Physicochemical analysis using NMR, MS and IR revealed the chemical structures of the sesquiterpenes, which were zaluzanin (1), 9a-hydroxyguaian-4(15), 10(14), 11(13)-triene-6, 12-olide (2), 3β-O-β-D-glucopyranosyl-8β-hydroxyguaian-4(15), 10(14)-diene-6,12-olide (3), 3-O-β-D-glucopyranosyl-8β-hydroxyguauan-10(14)-ene-6,12-olide (4), ixerinM (5), glucozaluzanin C (6), crepiside I (7), and ixerin D (8). This is the first time that these sesquiterpene lactones have been isolated from this plant. Compounds1, 2 and7 revealed relatively high cytotoxicities on human colon carcinoma cell and lung adenocarcinoma cell, while compounds5 and7 showed acyl-CoA: cholesterol acyltransferase (ACAT) inhibitory activity.

Phytol, SSADH inhibitory diterpenoid ofLactuca sativa

The succinic semialdehyde dehydrogenase (SSADH) inhibitory component was isolated from the EtOAc fraction ofLactuca sativa through repeated column chromatography; then, it was identified as phytol, a diterpenoid, based on the interpretation of several spectral data. Incubation of SSADH with the phytol results in a time-dependent loss of enzymatic activity, suggesting that enzyme modification is irreversible. The inactivation followed pseudo-first-order kinetics with the second-rate order constant of 6.15 x 10-2 mM-1min-1. Complete protection from inactivation was afforded by the coenzyme NAD+, whereas substrate succinic semialdehyde failed to prevent the inactivation of the enzyme; therefore, it seems likely that phytol covalently binds at or near the active site of the enzyme. It is postulated that the phytol is able to elevate the neurotransmitter GABA levels in central nervous system through its inhibitory action on one of the GABA degradative enzymes, SSADH.