Eun-Mi Ahn

Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway

Inhibition of angiogenesis is an attractive approach for the treatment of angiogenic diseases, such as cancer. Vascular endothelial growth factor (VEGF) is one of the most important activators of angiogenesis and interacts with the high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2. The pyranocoumarin compounds decursin and decursinol angelate isolated from the herb, Angelica gigas, are known to possess potent anti-inflammatory activities. However, little is known about their antiangiogenic activity or their underlying mechanisms. Here, we show the antiangiogenic effects of decursin and decursinol angelate using in vitro assays and in vivo animal experiments. Decursin and decursinol angelate inhibited VEGF-induced angiogenic processes in vitro, including proliferation, migration and tube formation of human umbilical vein endothelial cells. Decursin and decursinol angelate significantly suppressed neovessel formation in chick chorioallantoic membrane and tumor growth in a mouse model. The microvessel density in tumors treated with decursin for 14 days was significantly decreased compared with a vehicle control group. Decursin and decursinol angelate inhibited VEGF-induced phosphorylation of VEGFR-2, extracellular signal-regulated kinases and c-Jun N-terminal kinase mitogen-activated protein kinases. Taken together, these results demonstrate that decursin and decursinol angelate are novel candidates for inhibition of VEGF-induced angiogenesis.

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.

Carbohydrate derivatives from the roots of Brassica rapa ssp. campestris and their effects on ROS production and glutamate-induced cell death in HT-22 cells

Phytochemical investigation of the roots of Brassica rapa ssp. campestris led to the isolation of three new carbohydrate derivatives, namely sucrose 3,3,4-triisovalerate (2), sucrose 6,3,4-triisovalerate (3), and ethanone-1-C-β-d-glucopyranoside (3,7-anhydro-1-deoxy-d-glycero-d-gulo-2-octulose, 6), along with four known carbohydrate derivatives, 2,6,3,4-tetraisovalerate (1), ethyl β-d-glucopyranoside (4), n-butyl β-d-fructofuranoside (5), and n-pentyl β-d-fructofuranoside (7), which were initially isolated from plants of the Brassica genus. Structures of the isolated compounds were established by spectroscopic analyses, including UV, IR, MS, and NMR. All of the isolated carbohydrate derivatives were evaluated to determine their effect on ROS production and glutamate-induced cell death in HT-22 cells. Compound 6 showed the most significant ROS reduction and a protective effect with IC50 values of 69.4 ± 3.8 μM and 4.96 ± 0.32 μM, respectively, which were equivalent to those of the positive control, Trolox.

New indoles from the roots of Brassica rapa ssp. campestris

Two new indoles, 2-C-β-D-glucopyranosyl-1-methoxyindole-3-acetonitrile (1) and 6-hydroxy-1-methylindole3-acetonitrile (2), along with two known indoles [caulilexin C (3) and arvelexin (4)], were isolated from turnip roots (Brassica rapa ssp. campestris L.). The structures of the compounds were established on the basis of NMR, FAB-MS, and IR spectroscopic data.

The Ameliorative Effect of Sophoricoside on Mast Cell-Mediated Allergic Inflammation in Vivo and in Vitro

Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases.

Phenolic Compounds from the Roots of Brassica rapa ssp. campestris

A new benzyl α-D-fructofuranoside (3), along with six known phenol compounds, benzyl-β-D-glucopyranoside (1), dihydrosyringin (2), syringin (4), triandrin (5), phillyrin (6), and neoolivil-4-O-β-D-glucopyranoside (7), was isolated from the roots of Brassica rapa ssp. campestris L. for the first time. The structures of the compounds were established on the basis of NMR, MS, and IR spectroscopic data.

Decursinol angelate inhibits PGE2-induced survival of the human leukemia HL-60 cell line via regulation of the EP2 receptor and NFκB pathway

ABSTRACT Decursinol angelate (DA), an active pyranocoumarin compound from the roots of Angelica gigas, has been reported to possess anti-inflammatory and anti-cancer activities. In a previous study, we demonstrated that prostaglandin E2 (PGE2) plays a survival role in HL-60 cells by protecting them from the induction of apoptosis via oxidative stress. Flow cytometry and Hoechst staining revealed that PGE2 suppresses menadione-induced apoptosis, cell shrinkage, and chromatin condensation, by blocking the generation of reactive oxygen species. Treatment of DA was found to reverse the survival effect of PGE2 as well as restoring the menadione-mediated cleavage of caspase-3, lamin B, and PARP. DA blocked PGE2-induced activation of the EP2 receptor signaling pathway, including the activation of PKA and the phosphorylation of CREB. DA also inhibited PGE2-induced expression of cyclooxygenase-2 and the activation of the Ras/Raf/ Erk pathway, which activates downstream targets for cell survival. Finally, DA greatly reduced the PGE2-induced activation of NF-κB p50 and p65 subunits. These results elucidate a novel mechanism for the regulation of cell survival and apoptosis, and open a gateway for further development and combinatory treatments that can inhibit PGE2 in cancer cells.

Ribes fasciculatum var. chinense Attenuated Allergic Inflammation In Vivo and In Vitro

Ribes fasciculatum var. chinense MAX. (R. fasciculatum) has traditionally been used in Korea to treat inflammatory diseases. However, the exact mechanism that accounts for the anti-inflammatory effect of R. fasciculatum is not completely understood. We aimed to ascertain the pharmacological effects of R. fasciculatum on both compound 48/80- or histamine-induced scratching behaviors and 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of R. fasciculatum, we evaluated the effects of R. fasciculatum on the production of inflammatory mediators in LPS-stimulated macrophage cells. Treatment of R. fasciculatum significantly reduced compound 48/80- or histamine-induced the pruritus in mice. R. fasciculatum attenuated the AD symptoms such as eczematous, erythema and dryness and serum IgE levels in AD model. Additionally, R. fasciculatum inhibited the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The maximal rates of TNF-α and IL-6 inhibition by R. fasciculatum (1 mg/ml) were approximately 32.12% and 46.24%, respectively. We also showed that R. fasciculatum inhibited the activation of nuclear factor-kappa B in LPS-stimulated macrophages. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of R. fasciculatum as a potential molecule for use in the treatment of allergic inflammatory diseases.

Genistein-4′-O-α-L-rhamnopyranosyl-(1→2)- β-D-glucopyranoside from Sophora japonica (Leguminosae) ameliorates mast cell-mediated allergic inflammation in vivo and in vitro

Genistein-4′-O-α-L-rhamnopyranosyl-(1–2)- β-D-glucopyranoside (GRG) is one of constituents isolated from Sophora japonica (Leguminosae). It is known to exert various effects such as anti-inflammatory effect. However, the anti-allergic effects of GRG and its molecular mechanisms have yet to be clearly elucidated. In this study, we attempted to evaluate the effects of GRG on mast cell-mediated allergic inflammation in vitro and in vivo. We investigated to ascertain the pharmacological effects of GRG on compound 48/80-induced systemic anaphylaxis and experimental scratching behavior in mice. Additionally, to find a possible explanation for the anti-allergic mechanisms of GRG, we evaluated the regulatory effects of GRG on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that GRG reduced compound 48/80-induced systemic anaphylaxis and scratching behavior in mice. Additionally, GRG inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-8 and histamine as well as the activation of caspase-1 in PMACI-stimulated HMC-1. Taken together, the findings of this study provide a novel insight into the pharmacological actions of GRG as a potential molecule for use in the treatment of allergic inflammation diseases.

Recovery effect of phenylpropanoid glycosides from Magnolia obovata fruit on alloxan-induced pancreatic islet damage in zebrafish (Danio rerio).

Investigation of phytochemicals from Magnolia obovata fruit led to the isolation of three novel phenylpropanoid glycosides: obovatoside A-C (1-3) and two known phenylpropanoids, syringin (4) and pavonisol (5). The structures of 1-5 were determined by NMR, HRMS, IR and CD spectroscopic analyses. All compounds were evaluated for their effects on recovery from alloxan-induced pancreatic islet damage in zebrafish. All compounds increased the size of the injured pancreatic islet from 0.60- to 1.14-fold. Compounds 1 and 3-5 significantly increased glucose absorption in zebrafish.