cytellin and Acute-Lung-Injury

β-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of β-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that β-sitosterol (150-450 μg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of β-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, β-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of β-sitosterol (50, 200 mg·kg

Topics: A549 Cells; Acute Lung Injury; Animals; Antiviral Agents; Apoptosis; DEAD Box Protein 58; Dogs; Female; HEK293 Cells; Humans; Inflammation; Influenza A Virus, H1N1 Subtype; Interferon Lambda; Interferon Type I; Interferons; Lung; Madin Darby Canine Kidney Cells; Mice, Inbred BALB C; Plants; Signal Transduction; Sitosterols; STAT1 Transcription Factor

Dry citrus peel (Chenpi) is not only consumed as a dietary supplement, but also used for the treatment of respiratory diseases. Pinelliae Rhizoma Praeparatum (Banxia) is always used with Chenpi for the treatment of respiratory diseases, but β-sitosterol, the main active component in Banxia, as a food additive, shows no respiratory system activity. In the present study, the pharmacokinetic characters showed that the absorption of the active components of Chenpi was accelerated under pathological conditions combined with Banxia. Although the bioavailability of active components did not significantly change, the distribution of active components in tissues increased, particularly in the target organ. These results are consistent with the combination of Chenpi with β-sitosterol. Furthermore, the pharmacodynamics result also indicated that Chenpi combined with Banxia or β-sitosterol was able to ameliorate histopathologic damage and decrease the levels of inflammatory factors. The results suggest that pharmacokinetic interactions improve the pharmacological activity of Chenpi in respiratory diseases.

Topics: Acute Lung Injury; Animals; Citrus; Disease Models, Animal; Drugs, Chinese Herbal; Fruit; Lipopolysaccharides; Male; Pinellia; Plant Extracts; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sitosterols