Sudden exposure of nonacclimatized individuals to high altitude can easily lead to high altitude illnesses. High altitude pulmonary edema (HAPE) is the most lethal form of high altitude illness. The present study was designed to investigate the ability ofRhodiola crenulataextract (RCE), an herbal medicine traditionally used as an antiacute mountain sickness remedy, to attenuate hypoxia-induced pulmonary injury. Exposure of animals to hypobaric hypoxia led to a significant increase in pathological indicators for pulmonary edema, including the lung water content, disruption of the alveolar-capillary barrier, and protein-rich fluid in the lungs. In addition, hypobaric hypoxia also increased oxidative stress markers, including (ROS) production, (MDA) level, and (MPO) activity. Furthermore, overexpression of plasma (ET-1), (VEGF) in (BALF), and (HIF-1α) in lung tissue was also found. However, pretreatment with RCE relieved the HAPE findings by curtailing all of the hypoxia-induced lung injury parameters. These findings suggest that RCE confers effective protection for maintaining the integrity of the alveolar-capillary barrier by alleviating the elevated ET-1 and VEGF levels; it does so by reducing hypoxia-induced oxidative stress. Our results offer substantial evidence to support arguments in favor of traditional applications ofRhodiola crenulatafor antihigh altitude illness.

Melaleuca alternifolia concentrate (MAC) is the refined essential oil of the Australian native plant Melaleuca alternifolia. MAC has been reported to suppress the production of pro-inflammatory cytokines in both murine RAW264.7 macrophages and human monocytes stimulated with lipopolysaccharide (LPS). However, the mechanisms involved in this effect remain unclear. This study aims to delineate the molecular mechanisms that drive the anti-inflammatory activity of MAC and its active component, terpinen-4-ol, in macrophages. The effects of MAC on RAW264.7 cells were studied using western blotting, real-time PCR, an electrophoretic mobility shift assay (EMSA), and NF-$\kappa$B luciferase reporter assays. Our results showed that MAC significantly increased both the mRNA and protein levels of heme oxygenase-1 (HO-1) via p38 and JNK MAPK activation. In addition, we showed that MAC significantly increased the activation and nuclear translocation of NF-E2-related factor 2 (Nrf2), a key transcription factor regulating HO-1 induction. MAC was also associated with significant inhibition of iNOS expression, NO production, and NF-$\kappa$B activation. HO-1 was required for these anti-inflammatory effects as tin protoporphyrin IX (SnPPIX), an HO-1 inhibitor, abolished the effects of MAC on LPS-induced iNOS, NO, and NF-$\kappa$B activation. Our results indicate that MAC induces HO-1 expression in murine macrophages via the p38 MAPK and JNK pathways and that this induction is required for its anti-inflammatory activity.

Caffeic acid phenyl ester (CAPE) has been identified as an active component of propolis, a substance that confers diverse activities in cells of various origins. However, the molecular basis of CAPE‐mediated cellular activity remains to be clarified. Here, we show that CAPE preferentially induced S‐ and G₂/M‐phase cell‐cycle arrests and initiated apoptosis in human cervical cancer lines. The effect was found to be associated with increased expression of E2F‐1, as there is no CAPE‐mediated induction of E2F‐1 in the pre‐cancerous cervical Z172 cells. CAPE also up‐regulated the E2F‐1 target genes cyclin A, cyclin E and apoptotic protease activating of factor 1 (Apaf‐1) but down‐regulated cyclin B and induced myeloid leukemia cell differentiation protein (Mcl‐1). These results suggest the involvement of E2F‐1 in CAPE‐mediated growth inhibition and cell‐cycle arrest. Transient transfection studies with luciferase reporters revealed that CAPE altered the transcriptional activity of the apaf‐1 and mcl‐1 promoters. Further studies using chromatin immunoprecipitation assays demonstrated that E2F‐1 binding to the apaf‐1 and cyclin B promoters was increased and decreased, respectively, in CAPE‐treated cells. Furthermore, E2F‐1 silencing abolished CAPE‐mediated effects on cell‐cycle arrest, apoptosis and related gene expression. Taken together, these results indicate a crucial role for E2F‐1 in CAPE‐mediated cellular activities in cervical cancer cells.