Hyun-Wook Chang

Cytotoxicity and DNA Topoisomerases Inhibitory Activity of Constituents from the Sclerotium of Poria cocos

The bioactivity-guided fractionation of the methylene chloride extract of the sclerotium ofPoria cocos led to the isolation of (S)-(+)-turmerone (1), ergosterol peroxide (2), polyporenic acid C (3), dehydropachymic acid (4), pachymic acid (5), and tumulosic acid (6). Compounds4-6 exhibited moderate cytotoxicities, with IC50 values of 20.5, 29.1, and 10.4 αM, respectively, against a human colon carcinoma cell line. However,3-6 not only showed inhibitory activities as potent as etoposide used as a positive control on DNA topoisomerase II (36.1, 36.2, 43.9 and 66.7% inhibition at a concentration of 20 μM, respectively), but also inhibition of DNA topoisomerase I (55.8, 60.7, 43.5, and 83.3% inhibition at a concentration of 100 μM, respectively).

Inhibition of DNA topoisomerases I and II and cytotoxicity of compounds from Ulmus davidiana var. japonica.

Twenty five compounds including ten triterpenes (1–3, 5–11), six flavonoids (12–15, 24, 25), five lignans (17, 18, 21–23), two butenyl clohexnone glycosides (19–20), one fructofuranoside (16) and one fatty acid (4) were isolated from the roots of Ulmus davidiana var. japonica. The structures of those compounds were identified by comparing their physicochemical and spectral data with those of published in literatures. All the compounds were evaluated for DNA topoisomerase inhibitory activities and cytotoxicities. Among the purified compounds, 4 and 19 showed more potent inhibitory acitivities (IC50: 39 and 19 μM, respectively) than camptothecin, as the positive control (IC50: 46 μM) against topoisomerase I. Compounds, 4, 10, 12, 19, 24 and 25 showed strong inhibitory activities toward DNA topoisomerase II (IC50: 0.1, 0.52, 0.47, 0.42, 0.17 μM and 17 nM, respectively), which were more potent than that of etoposide as positive control (IC50: 20 μM). In A549 cell line, 5 and 6 showed cytotoxicities (IC50: 4 μM and 3 μM, respectively, with IC50 of camptothecin as positive control: 10.3 μM). In the HepG2 cell line, 3, 5 and 7 showed cytotoxicity (IC50: 4, 3 and 4 μM, respectively, with IC50 of camptothecin: 0.3 μM). Compounds 6, 12 and 23 showed cytotoxicities in the HT-29 cell line (IC50: 19, 19 and 15 μM, respectively, with IC50 of camptothecin: 2 μM).

Protective Constituents Against Sepsis in Mice from the Root Cortex of Paeonia suffruticosa

The bioassay-guided fractionation of protective agents against sepsis-induced lethality from the root cortex ofPaeonia suffruticosa ANDREWS (Ranunculaceae) led to the isolation of eight known compounds: paeonol (1), 2,5-dihydroxy-4-methoxyacetophenone (2), acetovanillone (3), paeonoside (4), paeoniflorin (5), oxypaeoniflorin (6), apiopaeonoside (7), and methyl 3-hydroxy-4-methoxybenzoate (8). Among them,3 showed the highest survival rate (100% with a dose of 30 mg/kgversus 17% for the control experiment) and reduced alanine aminotransferase level to be a half of the control value on the sepsis model induced by lipopolysaccharide/D-galactosamine.

Inhibition of DNA topoisomerases I and II of compounds from Reynoutria japonica.

Three anthraquinones (1, 2 and 4), three stilbenes (5, 6 and 7) and 3,5-dihydroxybenzyl alcohol (3) were isolated from Reynoutria japonica. Their structures were identified as emodin (1), emodin-8-O-β-d-glucoside (2), 3,5-dihydroxybenzyl alcohol (3), citreorosein (4), cis-resveratrol (5), trans-resveratrol (6) and trans-resveratrol-5-O-β-d-glucopyranoside (7) by comparing their physicochemical and spectral data with published data. Compound 3 was isolated for the first time from the Polygonaceae family. Among the purified compounds, 3 showed more potent inhibitory activity against topoisomerase I (IC50: 4 μM) than camptothecin, as the positive control (IC50: 18 μM). Compounds 3, 4, 5, 6 and 7 showed stronger inhibitory activities toward DNA topoisomerase II (IC50: 0.54, 14, 15, 0.77 and 3 μM, respectively) than the positive control, etoposide (IC50: 44 μM). Compounds 1 and 4 displayed weak cytotoxicities against human lung cancer (A549), ovarian cancer (SK-OV-3), human liver hepatoblastoma (HepG2) and colon adenocarcinoma (HT-29) cell lines.

Cytotoxic and DNA topoisomerases I and II inhibitory constituents from the roots of Aralia cordata.

Bioactivity-guided fractionation, based on the DNA topoisomerase inhibitory activity, lead to the isolation of five compounds (1–5) from the methylene chloride extract of the roots ofAralia cordata Thunb. (Araliaceae). These compounds were identified asent-pimara-8(14),15-dien-19-oic acid (1),ent-pimara-8(14),15-dien-18-oic acid (2), 16α-hydrogen-17-isovaleryloxy-ent-kau-ran-19-oic acid (3), 16α-hydroxy-17-isovaleryloxy-ent-kauran-19-oic acid (4) and dehydrofal-carindiol-8-acetate (5) from their spectral data. Compound3 was isolated for the first time from this plant, and also showed the strongest inhibition of both DNA topoisomerase I and II activities, with 53 and 96% inhibitions, respectively, at a concentration of 20 μM. However, all the compounds exhibited either weak or no cytotoxicities against the human colon carcinoma cell line (HT-29), the human breast carcinoma cell line (MCF-7) and human hepato blastoma cell line (HepG-2).

Protective constituents against sepsis in mice from the root barks of Ulmus davidiana var. japonica

In the course of isolating preventive agents against sepsis based on the in vivo assay model, eleven known compounds, (−)-catechin (1), catechin-7-O-β-apiofuranoside (2), catechin-7-O-α-Lrhamnopyranoside (3), catechin-3-O-α-L-rhamnopyranoside (4), catechin-7-O-β-d-glucopyranoside (5), butyl (+)-5′-methoxyisolariciresinol-9′-O-β-d-xylopyranoside (6), lyoniside (7), nudiposide (8), α-nigerose (9), butyl α-d-fructofuranoside (10), and procyanidin B3 (11) were isolated from the root barks of Ulmus davidiana var. japonica. Compounds 2, 6, and 8 significantly protected against sepsis in a mouse model with survival rates of mice exposed to 10 mg/kg of LPS/d-GalN ranged from 80%–100%. Among them, 8 exhibited the most potent protective effect and decreased the plasma levels of TNF-α, IL-10 and ALT activity.

n-Butyl-α-D-fructofuranoside Isolated from Ulmus davidiana Enhances Nrf2 Activity Through Activation of JNK

BACKGROUND The root bark of Ulmus davidiana Nakai (Ulmaceae), a traditional Korean medicinal plant, is used for treating inflammatory diseases. OBJECTIVE We investigated the Nrf2-activating effect of U. davidiana and identified a novel Nrf2 activator from its constituent compounds. METHODS Cytotoxicity was measured by MTT assay, and the Nrf2 activity was examined by luciferasereporter assay and western blot analysis. The expression of Nrf2-dependent antioxidant genes was estimated by RT-PCR. The signal pathway related to Nrf2 activation was analyzed by treating specific signaling inhibitors. Anti-inflammatory effects were determined using an NO assay and western blot analysis. RESULTS Ulmus davidiana and its constituent compounds, including catechin-3-O-α-L-rhamnopyranoside, α-nigerose, n-butyl α-D-fructofuranoside (NBF), and procyanidin B3, enhanced the transcriptional activity of Nrf2. Of these compounds, only NBF possessed a distinctive structure and exhibited ROS-independent Nrf2 activation. In addition, NBF significantly increased the nuclear translocation of Nrf2 and the expression of Nrf2-dependent detoxifying enzymes, including HO-1 and NQO-1, in dose-dependent manner. The Nrf2 activation induced by NBF was mediated by the phosphorylation of JNK. Consequently, pretreatment with NBF inhibited the LPS-induced expression of pro-inflammatory genes. CONCLUSION To the best of our knowledge, this is the first study to report on the Nrf2-activating effect of U. davidiana and NBF. Given the importance of Nrf2 as a negative regulator in various inflammatory diseases, NBF could be considered as a novel candidate for the prevention and treatment of inflammatory diseases.