Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo.

Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in Cordyceps sinensis (C. sinensis), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both in vitro and in vivo, whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both in vitro and in vivo Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured C. sinensis on COPD patients.

Sun X ，Feng X ，Zheng D ，Li A ，Li C ，Li S ，Zhao Z ... -  《-》

Nucleosides isolated from Ophiocordyceps sinensis inhibit cigarette smoke extract-induced inflammation via the SIRT1-nuclear factor-κB/p65 pathway in RAW264.7 macrophages and in COPD mice.

Sun X ，Dong Z ，Li N ，Feng X ，Liu Y ，Li A ，Zhu X ，Li C ，Zhao Z ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways.

Dang X ，He B ，Ning Q ，Liu Y ，Guo J ，Niu G ，Chen M ... -  《RESPIRATORY RESEARCH》

Baicalin attenuates inflammation by inhibiting NF-kappaB activation in cigarette smoke induced inflammatory models.

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) is a key player in the inflammatory response. Baicalin is an extract from roots of the plant scutellaria baicalensis. Many studies show that baicalin has anti-inflammatory, anti-bacterial and antiviral activities. Here we investigated the influence of baicalin on COPD inflammation and the mechanism of anti-inflammatory effect in vivo and in vitro. In vivo, COPD rat model was established by cigarette smoke (CS) exposure. Thirty-six Sprague-Dawley (SD) rats were randomly assigned to six experimental groups: control, CS, dexamethasone (DXM), and baicalin (20 mg/kg, 40 mg/kg, 80 mg/kg). The lung pathology was observed and leukocytes in bronchoalveolar lavage fluid (BALF) were counted by Optical microscope. Pulmonary function was measured by using an animal plethysmograph. The production of cytokines was measured by ELISA and the expression levels of NF-kappaB p65 protein were detected by immunohistochemistry. The results in vivo show CS exposure significantly increased the expression of IL-8, IL-6 and TNF-alpha in plasma and BALF and enhanced NF-kappaB p65 expression in the lungs. Baicalin treatment markedly attenuated the inflammatory effects of CS. In vitro, cell model was established by using cigarette smoke extract (CSE) to stimulate type II pneumocytes. Type II pneumocytes were also divided into six groups: control, CSE, pyrrolidine dithiocarbamate (PDTC), and baicalin (5 mumol, 10 mumol, 20 mumol). Cytokines levels were measured by ELISA. Expression of IkappaB and p65 phosphorylation was detected by western blotting. NF-kappaB DNA-binding activity was detected by EMSA. The results show that CSE resulted in increasing IL-8, IL-6 and TNF-alpha expression and activation of NF-kappaB. The proinflammatory effects of CSE were inhibited by treatment of baicalin in a dose-dependent manner. It can be concluded that baicalin has significant anti-inflammatory effects on CS induced COPD rat models and CSE-induced cell models, and the effectiveness increases with increasing baicalin dosage. The anti-inflammatory effect is likely achieved by inhibiting the NF-kappaB pathway.

Lixuan Z ，Jingcheng D ，Wenqin Y ，Jianhua H ，Baojun L ，Xiaotao F ... -  《-》

Down-regulated peroxisome proliferator-activated receptor γ (PPARγ) in lung epithelial cells promotes a PPARγ agonist-reversible proinflammatory phenotype in chronic obstructive pulmonary disease (COPD).

Lakshmi SP ，Reddy AT ，Zhang Y ，Sciurba FC ，Mallampalli RK ，Duncan SR ，Reddy RC ... -  《-》