4-Hydroxynonenal-induced GPR109A (HCA receptor) activation elicits bipolar responses, G -mediated anti-inflammatory effects and G -mediated cell death.

Background And Purpose: In this study, we examined the possibility that 4-hydroxynonenal (4-HNE) acting as a ligand for the HCA receptor (GPR109A) elicits both anti-inflammatory and cell death responses.

Experimental Approach: Agonistic activity of 4-HNE was determined by observing the inhibition of cAMP generation in CHO-K1-GPR109A-G cell line, using surface plasmon resonance (SPR) binding and competition binding assays with [ H]-niacin. 4-HNE-mediated signalling pathways and cellular responses were investigated in cells expressing GPR109A and those not expressing these receptors.

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.

(--)-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)-β-D-apiofuranoside-3-O-β-D-apiofuranosyl-(1 → 2)-β-D-glucopyranoside 2, (-)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-β-D-apiofuranoside-3-O-β-D-glucopyranoside 3, (-)-catechin-7-O-gallate-5-O-β-D-apiofuranoside-3-O-(2″-O-galloyl)-β-D-glucopyranoside 4, (-)-catechin-7-O-gallate-5-O-(5″″-trans-caffeoyl)-β-D-apiofuranoside 5, and (-)-catechin-7-O-gallate-5-O-(5″″-trans-feruloyl)-β-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-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.

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 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%.

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.

Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora flavescens.

Ethnopharmacological Relevance: The roots of Sophora flavescens have long been used in Chinese medicine for the treatment of fever, inflammatory disorders, ulcers and skin burns. Sophora flavescens contains flavonoids and alkaloids.

Aim Of The Study: This study was conducted to develop a plant-based anti-inflammatory agent focused on chronic inflammatory disorders.

Inhibition of DNA topoisomerases I and II and cytotoxicity by lignans from Saururus chinensis.

Thirteen lignans, erythro-austrobailignan-6 (1), meso-dihydroguaiaretic acid (2), sauchinone (3), 1'-epi-sauchinone (4), saucerneol D (5), manassantin B (6), manassantin A (7), nectandrin B (8), machilin D (9), saucerneol F (10), saucerneol G (11), saucerneol H (12) and saucerneol I (13), were isolated from the ethyl acetate extract of the roots of Saururus chinensis. Among these compounds, 5 showed potent inhibitory activities against DNA topoisomerase I and II, and 5, 6, 7 and 10 showed mild cytotoxicities against HT-29 (IC(50) values; 13, 12, 11, and 10 microM, respectively) and HepG2 cell lines (IC(50) values; 16, 11, 12, and 11 microM, respectively).

Protective effect of lignans against sepsis from the roots of Saururus chinensis.

In the course of isolating preventive agents from sepsis based on the in vivo assay model from the EtOAc extract of the roots of Saururus chinensis, twelve lignans, sarisan (1), erythro-austrobailignan-6 (2), meso-dihydroguaiaretic acid (3), saucerneol B (4), manassantin B (5), manassantin A (6), rel-(8R,8'R)-dimethyl-(7S,7'R)-bis(3,4-methylenedioxyphenyl)tetrahydro-furan (7), (+)-saururinone (8), sauchinone (9), sauchinone B (10), nectandrin B (11) and machilin D (12), were isolated. Compounds 9 and 10, at a dose of 10 mg/kg, increased survival rates to 80% from 20% for the control experiment, and decreased the plasma levels of tumor necrosis factor-alpha (TNF-alpha) and alanine aminotransferase (ALT) activity in mice administered LPS/D-GalN.

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 of Aralia cordata Thunb. (Araliaceae). These compounds were identified as ent-pimara-8(14), 15-dien-19-oic acid (1), ent-pimara-8(14), 15-dien-18-oic acid (2), 16alpha-hydrogen-17-isovaleryloxy-ent-kauran-19-oic acid (3), 16alpha-hydroxy-17-isovaleryloxy-ent-kauran-19-oic acid (4) and dehydrofalcarindiol-8-acetate (5) from their spectral data.

Two new benzofurans from Gastrodia elata and their DNA topoisomerases I and II inhibitory activities.

Two new benzofurans, 1-furan-2-yl-2-(4-hydroxyphenyl)-ethanone (1) and 5-(4-hydroxybenzyloxymethyl)-furan-2-carbaldehyde (2), together with five known compounds, 4-hydroxybenzyl methyl ether (3), 5-(hydroxymethyl)-furfural (4), gastrodin (5), beta-sitosterol (6) and beta-sitosterol glucoside (7) were isolated from the rhizome of Gastrodia elata Blume. In DNA topoisomerase I and II inhibition assays in vitro at a concentration of 20 microM, 1 showed potent inhibitory activity, 66% and 71% inhibition, respectively, compared to the positive control compounds, camptothecin and etoposide, 71% and 22% inhibition, respectively. All of these compounds exhibited weak or no cytotoxicities against human colon carcinoma cell line (HT-29), human breast carcinoma cell line (MCF-7) and human hepatocellular carcinoma cell line (HepG-2).

Meliae cortex extract exhibits anti-allergic activity through the inhibition of Syk kinase in mast cells.

The anti-allergic action of various Oriental medicinal herbs was investigated using in vitro and in vivo experimental models. Of these extracts, the ethanol extract of Meliae cortex (MC) exhibited the most potent activity in mast cells; its IC(50) values were 29+/-1.5 microg/ml for antigen stimulation and 57+/-3.

Agents protecting against sepsis from the roots of Angelica dahurica.

In the course of isolating agents preventing sepsis from the EtOAc extract of the roots of Angelica dahurica, four known furanocoumarins, isoimperatorin (1), oxypeucedanin (2), (+/-)-byakangelicin (3), and (+)-oxypeucedanin hydrate (4), were isolated as active compounds based on the in vivo assay model of sepsis induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN). Among them, 3 showed the highest survival rate (100% with a dose of 30 mg/kg versus 20% for the control experiment) and decreased the plasma levels of tumor necrosis factor-alpha and alanine aminotransferase in mice adminstered LPS/D-GalN.

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 of Paeonia 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/kg versus 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.

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 of Poria 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). Compounds 4-6 exhibited moderate cytotoxicities, with IC50 values of 20.5, 29.

Preventive agents against sepsis and new phenylpropanoid glucosides from the fruits of Illicium verum.

The bioassay-guided fractionation of preventive agents against lethality due to septic shock from the fruits of Illicium verum led to the isolation of two known racemic mixtures of phenylpropanoids, [1-(4'-methoxyphenyl)-(1 R,2 S and 1 S,2 R)-propanediol (1) and 1-(4'-methoxyphenyl)-(1 R,2 R and 1 S,2 S)-propanediol (2)], along with two known phenylpropanoid glucosides, [1-(4'-methoxyphenyl)-(1 S,2 R)-propan-1-ol 2-O-beta-D-glucopyranoside (3) and 1-(4'-methoxyphenyl)-(1 R,2 S)-propan-1-ol 2-O-beta-D-glucopyranoside ( 5)], and two new phenylpropanoid glucosides, [1-(4'-methoxyphenyl)-(1 S,2 S)-propan-1-ol 2- O-beta- D-glucopyranoside (4) and 1-(4'-methoxyphenyl)-(1 R,2 R)-propan-1-ol 2-O-beta-D-glucopyranoside (6)]. Their chemical structures were elucidated on the basis of spectroscopic studies. Among them, 1 exhibited the highest survival rate in a dose-dependent manner (100 % with a dose of 10 mg/kg against 40 % for the control experiment) and showed a reduction of the plasma alanine aminotransferase (ALT) value on the in vivo assay model of septic shock induced by tumor necrosis factor (TNF)-alpha.

Tyrosinase inhibitory prenylated flavonoids from Sophora flavescens.

For the purpose of the development of a skin-whitening agent, Sophora flavescens was evaluated for tyrosinase inhibitory activity and its active principles were identified following activity-guided isolation. The ethanol extract and dichloromethane fraction from S. flavescens showed significant inhibition of mushroom tyrosinase.