A new kaurane diterpenoid from Isodon inflexus.

A new 7,20-epoxy kaurane diterpenoid, 15-acetyldemethylkamebacetal A (1) and six known kaurane diterpenoids (2-7) were isolated from the aerial parts of Isodon inflexus in nuclear transcription factor-κB (NF-κB)-dependent reporter gene assay-guided fractionation. Their chemical structures were determined on the basis of extensive spectroscopic analysis (UV, IR, MS, 1D- and 2D-NMR) and comparison with literature data. The isolated compounds were evaluated for their inhibitory effects on TNF-α-induced NF-κB activation, and all compounds exhibited NF-κB inhibitory activities with IC50 values ranging from 1.

Cryptopleurine targets NF-κB pathway, leading to inhibition of gene products associated with cell survival, proliferation, invasion, and angiogenesis.

Background: Cryptopleurine, a phenanthroquinolizidine alkaloid, was known to exhibit anticancer activity; however, the underlying mechanism is poorly understood. Because the nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, and development and progression of cancer, we investigated the effects of cryptopleurine on tumor necrosis factor alpha (TNF-α)-induced NF-κB activation pathway and on the expression of NF-κB-regulated gene products associated with many pathophysiological processes.

Methodology And Principal Finding: MDA-MB231, MDA-MB435, MCF-7, HEK293, RAW264.

Effects of astilbic acid on airway hyperresponsiveness and inflammation in a mouse model of allergic asthma.

Bronchial asthma is characterized by chronic lung inflammation, airway hyperresponsiveness (AHR), and airway remodeling. Astilbic acid, extracted from the medicinal herb Astilbe chinensis, is used as a headache remedy in traditional medicine and has anti-pyretic and analgesic effects. However, the effect of astilbic acid on asthma remains to be established.

Hepatoprotective effects of Sedum sarmentosum on D-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure.

The hepatoprotective effects of sarmentosin-containing extracts of Sedum sarmentosum (SS) in D-galactosamine (D-GalN) / lipopolysaccharide (LPS)-induced fulminant hepatic failure mouse model. Pretreatment with SS markedly protected mice from lethal liver injury, which has known to be associated with an abrupt elevation of serum tumor necrosis factor (TNF)-α level. Indeed, SS significantly blocked the elevation of TNF-α and alanine aminotransferase and aspartate aminotransferase as well.

Attenuation of experimental murine colitis by acanthoic acid from Acanthopanax koreanum.

Acanthoic acid (AA) is a pimaradiene diterpene isolated from Acanthopanax koreanum. We examined the effect of AA in dextran sulfate sodium (DSS)-induced colitis. AA (100 mg/kg or 300 mg/kg) was administered p.

Oleanane-type triterpenoids from Aceriphyllum rossii and their cytotoxic activity.

The hexane-soluble fraction of the roots of Aceriphyllum rossii was used to isolate seven new oleanane-type triterpenoids, aceriphyllic acids C-I (1-7), together with seven known triterpenoids. The structures of aceriphyllic acids C-I were determined as 3alpha-hydroxyolean-12-en-23,29-dioic acid (1), 3beta-hydroxyolean-12-en-23,29-dioic acid (2), 3beta,23-dihydroxyolean-12-en-29-oic acid (3), 3alpha-O-acetylolean-12-en-23,27-dioic acid (4), 3alpha-O-caffeoylolean-12-en-27-oic acid (5), 3alpha-O-acetylolean-12-en-23,29-dioic acid (6), and 3alpha-hydroxyolean-12-en-23-al-27-oic acid (7) by spectroscopic analyses. In the evaluation of the in vitro cytotoxicity of these compounds against the MCF-7 and LLC cancer cell lines, compounds 10 and 13 exhibited cytotoxic activity against the LLC cancer cell line with IC(50) values of 7.

Cytotoxic triterpenoids from the rhizomes of Astilbe chinensis.

Six new triterpenoids (1-6) with a carboxylic acid functionality at C-27 were isolated from the rhizomes of a Korean native perennial herb, Astilbe chinensis, along with nine known triterpenoids. The structures of 1-6 were elucidated on the basis of spectroscopic data interpretation. All compounds isolated were evaluated for cytotoxic effects against a small panel of human cancer lines.

Bisacurone inhibits adhesion of inflammatory monocytes or cancer cells to endothelial cells through down-regulation of VCAM-1 expression.

Bisacurone, one of the active compounds of the traditionally used indigenous herb Curcuma longa Linne (Zingiberaceae), has anti-oxidant, anti-inflammatory, and anti-metastatic activities. We studied how the level of vascular cell adhesion molecule-1 (VCAM-1), one of the key molecules in the development of atherosclerosis as well as carcinogenesis and metastasis, might be affected by bisacurone in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs). Bisacurone dose-dependently inhibited TNF-alpha-mediated expression of VCAM-1.

Comparison of suppressive effects of demethoxycurcumin and bisdemethoxycurcumin on expressions of inflammatory mediators in vitro and in vivo.

Demethoxycurcumin and bisdemethoxycurcumin are the main active ingredients isolated from Curcumae Longae Radix. Recent studies demonstrated that both compounds exhibit antioxidative and anti-inflammatory effects as well as effects on cancer cell lines. In this study, we compared the activities of demethoxycurcumin and bisdemethoxycurcumin, and both compounds were evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, inducible nitric oxide synthase (iNOS), cycloxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB) activity in a RAW 264.

A diterpenoid acanthoic acid from Acanthopanax koreanum protects against D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice.

The hepatoprotective effects of a diterpenoid acanthoic acid isolated from Acanthopanax koreanum NAKAI were evaluated in a D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure mouse model. Mice were pretreated orally with acanthoic acid 12 and 1 h before intraperitoneal injection of D-galactosamine and lipopolysaccharide. Pretreatment with the compound markedly reduced lethal liver injury in experimental animals.

Hypoxia-inducible factor-1 and nuclear factor-kappaB inhibitory meroterpene analogues of bakuchiol, a constituent of the seeds of Psoralea corylifolia.

Two new meroterpenoids, 12,13-dihydro-12,13-dihydroxybakuchiol (2) and (12'S)-bisbakuchiol C (3), were isolated from the seeds of Psoralea corylifolia L. (Fabaceae). The structures of 2 and 3 were elucidated by spectroscopic and chemical methods.

Triterpenoids and diarylheptanoids from Alnus hirsuta inhibit HIF-1 in AGS cells.

Bioassay-guided fractionation and purification of the EtOAc soluble fraction from the MeOH extract of the stem bark of Alnus hirsuta (Betulaceae), using an in vitro HIF-1 assay, led to the isolation of four triterpenoids (1-4) and six diarylheptanoids (5-10). Their structures were determined by comparison with the physicochemical and spectroscopic data in the literature. These compounds were investigated for their effects on the hypoxia-induced HIF-1 activation using an HIF-1a mediated reporter gene assay in AGS cells.

Diarylheptanoids from Alnus hirsuta inhibit the NF-kB activation and NO and TNF-alpha production.

Six diarylheptanoids (1-6) from the stem bark of Alnus hirsuta were investigated for their inhibitory activity against LPS-induced NF-kB activation and NO and TNF-alpha production. Among them, compounds 2, 3, and 6 displayed inhibitory activity against NF-kB activation and NO and TNF-alpha production with IC50 values of 9.2-9.

In vitro and in vivo antiallergic effect of the fructus of Evodia rutaecarpa and its constituents.

The unripe fruit of Evodia rutaecarpa (JUSS) BENTH (ER, Family Rutaceae) has been used frequently as a traditional medicine against inflammatory diseases in Korea, China and Japan. To evaluate antiallergic effect of ER, we isolated its main constituents, evodiamine and rutaecarpine, and evaluated in vivo their inhibitory effects against passive cutaneous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors by compound 48/80. ER and its constituents, evodiamine and rutaecarpine, potently inhibited PCA reaction and scratching behaviors in mice, although ER weakly inhibited scratching behaviors.

Phenanthroquinolizidine alkaloids from the roots of Boehmeria pannosa potently inhibit hypoxia-inducible factor-1 in AGS human gastric cancer cells.

A bioassay-guided phytochemical investigation on the methanol extract of Boehmeria pannosa, using a HIF-1-mediated reporter gene assay, led to the isolation of two phenanthroquinolizidine alkaloids, (-)-cryptopleurine (1) and (-)-(15R)-hydroxycryptopleurine (2). The structure of the new compound 2 was determined by spectroscopic methods. Compounds 1 and 2 potently inhibited the hypoxia-induced expression of a reporter gene under the control of a hypoxia response element (HRE) with IC(50) values of 8.

Anti-inflammatory principles from the fruits of Evodia rutaecarpa and their cellular action mechanisms.

The fruits of Evodia rutaecarpa Benth (Rutaceae) has long been used for inflammatory disorders and some anti-inflammatory actions of its constituents such as dehydroevodiamine, evodiamine and rutaecarpine were previously reported. Since the pharmacological data is not sufficient to clearly establish the scientific rationale of anti-inflammatory medicinal use of this plant material and the search for its active principles is limited so far, three major constituents (evodiamine, rutaecarpine, goshuyuamide II) were evaluated for their anti-inflammatory cellular action mechanisms in the present study. From the results, evodiamine and rutaecarpine were found to strongly inhibit prostaglandin E2 synthesis from lipopolysaccharide-treated RAW 264.

Inhibition of protein tyrosine phosphatase 1B by diterpenoids isolated from Acanthopanax koreanum.

Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a therapy to treat type 2 diabetes and obesity. In our preliminary screening study on the PTP1B inhibitory activity, a CH2Cl2-soluble extract of the roots of Acanthopanax koreanum (Araliaceae) was found to inhibit PTP1B activity at 30 microg/ml. Eight diterpenoids were isolated from the active fraction and were evaluated for their inhibitory effect on PTP1B.

Inhibition of trypsin-induced mast cell activation by acanthoic acid.

Acanthoic acid (AA) is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum (Araliaceae). In the present study, we examined whether AA has the inhibitory effect on the production of inflammatory mediators and activating signals induced in trypsin-treated human leukemic mast cell-1 (HMC-1). HMC-1 cells were stimulated with trypsin (100 nM) in the presence or absence of AA (1, 10, and 100 microg/ml).

Fungal metabolites, sorbicillinoid polyketides and their effects on the activation of peroxisome proliferator-activated receptor gamma.

A new sorbicillinoid polyketide, dihydrotrichodimerol (2), along with known trichodimerol (1), and rezishanones C (3) and D (4) were isolated by bioassay-guided fractionation from an unidentified fungal strain. Dihydrotrichodimerol (2) specifically activated peroxisome proliferator-activated receptor gamma with an ED50 value of 80 ng/ml as measured by a transactivation assay using a chimeric hPPAR/GAL4 system without affecting peroxisome proliferator-activated receptors alpha and sigma. On the other hand, compounds 1 and 2 suppressed the production of tumor necrosis factor-alpha and nitric oxide in LPS-stimulated RAW264.

Gymnasterkoreayne G, a new inhibitory polyacetylene against NFAT transcription factor from Gymnaster koraiensis.

A new polyacetylene, gymnasterkoreayne G (1) and seven known (2--8) constituents were isolated from the leaves of Gymnaster koraiensis. Base on extensive 1D and 2D NMR spectroscopic data, the structure of the new compound was identified as erythro-8(S)-9(Z),16-heptadecadiene-4,6-diyne-2,3,8-triol. Isolated compounds were evaluated for their ability to inhibit NFAT transcription factor.

Solanoflavone, a new biflavonol glycoside from Solanum melongena: seeking for anti-inflammatory components.

A new biflavonol glycoside named as solanoflavone (1) was isolated from aerial part of Solanum melongena. The chemical structure was elucidated as isorhamnetin-3-O-beta-D-glucopyranoside-(4'-->O-->4''')-galangin-3''-O-beta-D-glucopyranoside on the basis of physicochemical and spectroscopic methods, including 2D NMR spectral techniques.

Inhibition of interleukin-8 production in the human colonic epithelial cell line HT-29 by 18 beta-glycyrrhetinic acid.

Interleukin (IL)-8 plays a central role in the initiation and maintenance of inflammatory responses in the inflammatory bowel disease. The proinflammatory cytokine-mediated production of IL-8 requires activation of various kinases, which leads to the I kappa B degradation and NF-kappa B activation. We investigated the role of 18 beta-glycyrrhetinic acid (GA), a saponin isolated from licorice roots, on TNF-alpha-induced IL-8 production in human colonic epithelial cells.

The inhibition of diacylglycerol acyltransferase by terpenoids from Youngia koidzumiana.

The EtOAc extract of Youngia koidzumiana significantly inhibited the diacylglycerol acyltransferase (DGAT) from rat liver microsomes. Bioactivity-guided fractionation led to the isolation of nine compounds, the structures of which were established using physicochemical and spectral data. Of the isolated compounds, oleanolic acid (2), methyl ursolate (7) and corosolic aicd (8) inhibited DGAT, with IC50 values of 31.