Two new conjugated ketonic fatty acids from the stem bark of Juglans mandshurica.

The present study was designed to isolate and characterize novel chemical constituents of the stem bark of Juglans mandshurica Maxim. (Juglandaceae). The chemical constituents were isolated and purified by various chromatographic techniques. The structures of the compounds were elucidated on the basis of spectral data (1D and 2D NMR, HR-ESI-MS, CD, UV, and IR) and by the comparisons of spectroscopic data with the reported values in the literatures. Two long chain polyunsaturated fatty acids (1 and 2) were obtained and identified as (S)-(8E,10E)-12-hydroxy-7-oxo-8,10-octadecadienoic acid (1) and (S)-(8E, 10E)-12-hydroxy-7-oxo-8,10-octadecadienoic acid methyl ester (2). To the best of our knowledge, this is the first report on the isolation and structural elucidation of the two new conjugated ketonic fatty acids from this genus.

Chemical constituents from the aerial parts of Melandrium firmum.

Two new anthraquinones, melrubiellin C (1) and melrubiellin D (2), were isolated from the aerial parts of Melandrium firmum Rohrbach, together with eight known compounds (3-10). The structures of these compounds were elucidated using 1D and 2D NMR (COSY, HMQC, HMBC and NOESY) experiments. All isolated compounds were tested for their cytotoxicity against NCI-H460, Hep G2, MKN-28 and A-549 cells. Of these 10 compounds, 1 and 2 exhibited moderate cytotoxicity with IC50 values ranging from 9.54 to 32.41 µM.

Chemical constituents from the leaves of Juglans mandshurica.

Two new (1 and 3) and two known diarylheptanoids (2 and 4), along with two tetralones (5 and 6), one naphthoquinone (7), four phenylpropanoids (8-11), and one phenol (12) were isolated from the leaves of Juglans mandshurica. Their structures were elucidated on the basis of spectral and chemical data. Compounds 2 and 10 are firstly isolated from this plant and 8 and 12 were isolated from the Juglans genus for the first time. Among these compounds, only 7 exhibited moderate cytotoxicities against cultured MGC-803, A549, K562, and HeLa tumor cell lines with IC50 values of 25.90, 28.60, 39.06, 44.90 µM, respectively.

Cytotoxic anthraquinone dimers from Melandrium firmum.

Two new anthraquinone dimers, melrubiellin A (1) and melrubiellin B (2), were isolated from the aerial part of Melandrium firmum Rohrbach, along with seven known compounds (3-9). The structures of these compounds were elucidated by spectral analyses, including 1D and 2D NMR (COSY, HMQC, HMBC and NOESY) experiments. Compound 1 and 2 exhibited significant cytotoxicity towards HeLa, NCI-H460, Hep G2, Hep 3B and MKN-28 cell lines with IC50 values ranging from 5.26 to 81.16 µM.

Inhibitory effects of (-)-loliolide on cellular senescence in human dermal fibroblasts.

Cellular senescence influences tumor suppression and progress, tissue repair and regeneration, tissue and organismal aging, and age-related diseases. Aging intervention might be an advantageous target for prevention and treatment of diverse age-related diseases. In this study, we investigated whether (-)-loliolide purified from the crude extract of Polygonum aviculare exerted inhibitory activity against cellular senescence in human dermal fibroblasts (HDFs). (-)-Loliolide diminished senescence-associated ß-galactosidase activity (SA-ß-gal), the level of p21 protein, and the level of reactive oxygen species in senescent cells induced by adriamycin treatment. (-)-Loliolide also attenuated SA-ß-gal activity in HDFs under replicative senescence. These findings imply that (-)-loliolide rescues cellular senescence in HDFs and might be useful for the development of dietary supplements or cosmetics that ameliorate tissue aging or age-associated diseases.

Quercetin-3-O-ß-D-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells.

Cellular senescence is known to contribute to tissue aging, a variety of age-related diseases, tissue regeneration, and cancer. Therefore, aging intervention might be useful for prevention of aging as well as age-related disease. In this study, we investigated compounds from Polygonum aviculare to determine if they inhibited cellular senescence in human primary cells, human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs). Ten compounds from P. aviculare were purified and their inhibitory effects on adriamycin-induced cellular senescence were measured by observing senescence-associated ß-galactosidase (SA-ß-gal) activity and reactive oxygen species. Among them, compound 9 (quercetin-3-O-ß-D-glucuronide) showed inhibitory effects against cellular senescence in HDFs and HUVECs treated with adriamycin. Additionally, compound 9 rescued replicative senescence in HDFs and HUVECs. These data imply that compound 9 represses cellular senescence in human primary cells and might be useful for the development of dietary supplements or cosmetics that ameliorate tissue aging or aging-associated diseases.

Inhibitory effects of juglanin on cellular senescence in human dermal fibroblasts.

Cellular senescence contributes to tissue and organismal aging, tumor suppression and progress, tissue repair and regeneration, and age-related diseases. Thus, aging intervention might be a promising target for treatment and prevention of diverse age-related diseases. In the present study, we investigated whether juglanin purified from the crude extract of Polygonum aviculare exerted inhibitory activity against cellular senescence in human dermal fibroblasts (HDFs). Juglanin decreased senescence-associated ß-galactosidase activity (SA-ß-gal) and the level of reactive oxygen species in senescent cells induced by adriamycin treatment. Juglanin also repressed SA-ß-gal activity in HDFs under replicative senescence. These results suggest that juglanin represses cellular senescence in HDFs and might be useful for the development of dietary supplements or cosmetics that alleviate tissue aging or age-related diseases.

(--)-Catechin glycosides from Ulmus davidiana.

Extensive chromatographic separation of the n-BuOH soluble fraction obtained from the stem and root barks of U. davidiana resulted in five hitherto unknown compounds together with a known one (-)-catechin 1. Structures of the five compounds were elucidated by chemical and spectroscopic analyses, to be (-)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-ß-D-apiofuranoside-3-O-ß-D-apiofuranosyl-(1 → 2)-ß-D-glucopyranoside 2, (-)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-ß-D-apiofuranoside-3-O-ß-D-glucopyranoside 3, (-)-catechin-7-O-gallate-5-O-ß-D-apiofuranoside-3-O-(2″-O-galloyl)-ß-D-glucopyranoside 4, (-)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-ß-D-apiofuranoside 5, and (-)-catechin-7-O-gallate-5-O-(5″″-trans-feruloyl)-ß-D-apiofuranoside 6.

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-ß-D-glucoside (2), 3,5-dihydroxybenzyl alcohol (3), citreorosein (4), cis-resveratrol (5), trans-resveratrol (6) and trans-resveratrol-5-O-ß-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.

Discrimination of Phellodendron amurense and P. chinense based on DNA analysis and the simultaneous analysis of alkaloids.

Phellodendri Cortex is the bark of the stems of Phellodendron amurense Ruprecht or P. chinense Schneider (Rutaceae), which is orginated from periderm. The internal transcribed spacer sequences of 20 originated plants and identified samples were analyzed. The result showed that the 99% of the base sequences of P. amurense were identical to that of P. chinense, but the differentiation of P. amurense and P. chinense was difficult. In addition, the ribulose-1, 5-bisphospate carboxylase large subunit (rbcL) intergenic spacer sequences of specific parts produced the same result. However, when the analysis was carried out by using the RAPD (randomly amplification polymorphism DNA) analysis method, which utilizes 48 randomly primers, it allowed us to confirm the polymorphism of P. amurense and P. chinense in 12 primers. A high-performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous quantitation of berberine, palmatine and jatrorrhizine in a traditional herbal drug, Phellodendri Cortex. The HPLC method was applied successfully to the quantification of three constituents in the extract of twenty Phellodendri Cortex. The results indicated that the established HPLC and RAPD methods are suitable for the quantitative analysis and the quality control multi-simultaneous discrimination in Phellodendri Cortex.

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-ß-apiofuranoside (2), catechin-7-O-α-Lrhamnopyranoside (3), catechin-3-O-α-L-rhamnopyranoside (4), catechin-7-O-ß-D-glucopyranoside (5), butyl (+)-5'-methoxyisolariciresinol-9'-O-ß-D-xylopyranoside (6), lyoniside (7), nudiposide (8), α-nigerose (9), butyl α-D-fructofuranoside (10), and procyanidin B(3) (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.

Anti-asthmatic effects of Angelica dahurica against ovalbumin-induced airway inflammation via upregulation of heme oxygenase-1.

Asthma is a chronic immune inflammatory disease characterized by variable airflow obstruction. The present study was undertaken to assess the effects of an Angelica dahurica Bentham et Hooker ethanolic extract (AD) on airway inflammation in an ovalbumin (OVA)-induced airway inflammation model. Mice that received AD displayed significantly lower airway eosinophilia, cytokine levels, including interleukin (IL)-4, IL-5, and tumor necrosis factor (TNF)-alpha levels, mucus production and immunoglobulin (Ig)E, compared with OVA-induced mice. In our experiments, AD treatment reduced airway inflammation and suppressed oxidative stress in the OVA-induced asthma model, partly via induction of heme oxygenase (HO)-1. The effects of AD on OVA-induced HO-1 induction were partially reversed by the HO-1 inhibitor, tin protoporphyrin (SnPP). Our results clearly indicate that AD is a suppressor of airway allergic inflammation, and may thus be effectively used as an anti-inflammatory drug in the treatment of asthma.

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 (IC(50): 39 and 19 µM, respectively) than camptothecin, as the positive control (IC(50): 46 µM) against topoisomerase I. Compounds, 4, 10, 12, 19, 24 and 25 showed strong inhibitory activities toward DNA topoisomerase II (IC(50): 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 (IC(50): 20 µM). In A549 cell line, 5 and 6 showed cytotoxicities (IC(50): 4 µM and 3 µM, respectively, with IC(50) of camptothecin as positive control: 10.3 µM). In the HepG2 cell line, 3, 5 and 7 showed cytotoxicity (IC(50): 4, 3 and 4 µM, respectively, with IC(50) of camptothecin: 0.3 µM). Compounds 6, 12 and 23 showed cytotoxicities in the HT-29 cell line (IC(50): 19, 19 and 15 µM, respectively, with IC(50) of camptothecin: 2 µM).

Topoisomerase I and II inhibitory constituents from the bark of Tilia amurensis.

Two coumarins (1 and 6), one flavan-3-ol (2), one fatty acid (3), and two lignan glycosides (4 and 5) were isolated from the EtOAc and CH(2)Cl(2) extract of the bark of Tilia amurensis. Their chemical structures were identified by comparing their physicochemical and spectral data with those of published in literatures. Compounds 4, 5, and 6 were isolated from Tilia genus for the first time. Compounds 2 and 3 showed potent inhibitory activity against both DNA topoisomerase I (IC(50) values; 49 microM and 4 microM, respectively, with 18 microM of positive control compound, comptothecin) and DNA topoisomerase II (IC(50) values; 13 microM and 3 microM, respectively, with 50 microM of positive control compound, etoposide). However, all compounds did not showed cytotoxicity against the human colon adenocarcinoma cell line (HT-29), the human breast adenocarcinoma cell line (MCF-7), and human liver hepatoblastoma cell line (HepG-2).

Lignans from the roots of Saururus chinensis.

Four new lignans, saucerneol F (1), saucerneol G (2), saucerneol H (3), and saucerneol I (4), were isolated from the EtOAc extract of the roots of Saururus chinensis, together with one known compound, saucerneol D (5). The structures of compounds 1-4 were elucidated by spectroscopic analysis. These compounds showed cytotoxic activities against HT-29, MCF-7, and HepG-2 cell lines.

Chemical constituents of Melandrium firmum Rohrbach and their anti-inflammatory activity.

In our ongoing search for anti-inflammatory agents originating from Korean medicinal plants, we found that the hexane and BuOH fractions of the MeOH extract from the whole plants of Melandrium firmum Rohrbach inhibited 5-lipoxygenase (5-LOX) activity. By activity-guided fractionation, eleven compounds, alpha-spinaterol (1), ursolic acid (2), ergosterol peroxide (3), alpha-spinaterol glucoside (4), 2-methoxy-9-beta-D-ribofuranosyl purine (5), aristeromycin (6), ecdysteron (7), polypodoaurein (8), (-)-bornesitol (9), mannitol (10) and cytisoside (11) were isolated from the hexane and BuOH fractions using column chromatography. Compounds 2, 5, 6, 8, 9, 10 and 11 were isolated for the first time from this plant. Compounds 1, 3, 4 and 7 inhibited 5-LOX activity with IC50 values of 21.04 microM, 42.30 microM, 32.82 microM, and 17.18 microM, respectively.

A new stilbene glucoside from the roots of Polygonum multiflorum Thunb.

One new stilbene glucoside (6), along with five known compounds (1-5), were isolated from the roots of Polygonum multiflorum Thumb., and their chemical structures established based on physicochemical and spectroscopic data. Of the compounds, compound 3 showed DNA topoisomerase I and II inhibitory activities.