(Z)-3α-(1,3-Dioxoisoindolin-2-yl)-17(20)-pregnene

The title compound, C29H37NO2, crystallized with two independent mol­ecules in an asymmetric unit in which the conformation of the cyclo­hexyl ring of the pregnene moiety bonded to the 3α-(1,3-dioxoisoindolin-2-yl)- ring system differs: in one mol­ecule it is in a chair conformation, while in the other it exhibits a half-chair conformation. The other six-membered rings in the pregnene moiety are in chair conformations and the five-membered rings are in envelope forms in both mol­ecules. In both mol­ecules, the 3α-(1,3-dioxoisoindolin-2-yl)- ring systems are individually approximately planar, with r.m.s. devtaions 0.0148 and 0.0264 Å. The structure is consolidated by inter­molecular C—H⋯O hydrogen-bonding inter­actions involving the carbonyl O atoms and methyl, methyl­ene and methyl­idyne groups, resulting in a two-dimensional structure

2α-Acet­oxy-5α-methoxy­caryophyll-8(15)-en-3-one

The title compound, C18H28O4, crystallizes with two mol­ecules in the asymmetric unit. Both mol­ecules have similar conformations of nine-membered rings, which are trans-fused with cyclo­butane fragments. The puckering amplitudes (q2) of the cyclo­butane rings are 0.2451 (2) and 0.2526 (2) Å

(S,E)-N-Methyl-4-[(S)2,6,6-trimethyl-4-oxocyclo­hex-2-en­yl]but-3-en-2-aminium chloride

The title compound, C14H24NO+·Cl−, crystallizes with four independent mol­ecules in the asymmetric unit. It was isolated from plant Pachysandra terminalis Siebold & Zucc. The six-membered ring has a conformation close to an envelope. In the crystal, N—H⋯Cl hydrogen-bonding inter­actions exist between secondary ammonium groups and free chloride anions, resulting in a one-dimensional supra­molecular structure oriented along [100]. The crystal studied was found to be a two-component non-merohedral twin with twin law [00/00/101], the fractional contribution of the minor component being approximately 33%

Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-κB and activating Nrf2/HO-1 signaling pathways

Sivelestat sodium (SIV), a neutrophil elastase inhibitor, is mainly used for the clinical treatment of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). However, studies investigating the effects of SIV treatment of ALI are limited. Therefore, this study investigated the potential molecular mechanism of the protective effects of SIV against ALI. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with tumor necrosis factor α (TNF-α), and male Sprague-Dawley rats were intratracheally injected with Klebsiella pneumoniae (KP) and treated with SIV, ML385, and anisomycin (ANI) to mimic the pathogenetic process of ALI in vitro and in vivo, respectively. The levels of inflammatory cytokines and indicators of oxidative stress were assessed in vitro and in vivo. The wet/dry (W/D) ratio of lung tissues, histopathological changes, inflammatory cells levels in bronchoalveolar lavage fluid (BALF), and survival rates of rats were analyzed. The JNK/NF-κB (p65) and Nrf2/HO-1 levels in the HPMECs and lung tissues were analyzed by western blot and immunofluorescence analyses. Administration of SIV reduced the inflammatory factors levels, intracellular reactive oxygen species (ROS) production, and malondialdehyde (MDA) levels and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues. Meanwhile, SIV alleviated pathological injuries, decreased the W/D ratio, and inflammatory cell infiltration in lung tissue. In addition, SIV also inhibited the activation of JNK/NF-κB signaling pathway, promoted nuclear translocation of Nrf2, and upregulated the expression of heme oxygenase 1 (HO-1). However, ANI or ML385 significantly reversed these changes. SIV effectively attenuated the inflammatory response and oxidative stress. Its potential molecular mechanism was related to the JNK/NF-κB activation and Nrf2/HO-1 signaling pathway inhibition. This further deepened the understanding of the protective effects of SIV against ALI

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

A Novel Triterpene from Centella asiatica

A novel triterpene, 2α,3β,20,23-tetrahydroxyurs-28-oic acid (1), was isolated from the aerial part of Centella asiatica. Its structure was elucidated by spectroscopic methods, including 2D-NMR spectra. It displayed no activity against Hela and A549 cell lines at concentrations of 10 and 30 μg/mL, respectively

Two new antitumor diterpenes from Pinus sylvestris

Two new diterpenes, 15-ethyl-18-methyl pinifolate (1) and 18-hydroxy-labda-8(17),13E-dien-15-acetate (2), were isolated from the needles of Pinus sylvestris. Their structures were elucidated by spectroscopic methods, including 2D-NMR spectra. Compound 1 exhibited the significant cytotoxic activity against the human carcinoma cell lines Hela, SK-N-SH and BEL-7402 in vitro. (c) 2007 Hong Quan Duan. Published by Elsevier B. V. on behalf of Chinese Chemical Society. All rights reserved