Inflammation is the first step that leads to inflammatory cell migration, cytokine release, and myofibroblast formation. Myofibroblasts can deposit excess amounts of extracellular matrix. Cyclooxygenase (COX) inhibitor exhibits strong anti-inflammatory response; however, this is usually achieved with undesirable side effects. In this study, we demonstrated the effects of the fluorine-modified rutaecarpine (RUT), fluoro-2-methoxyrutaecarpine (F-RUT), in inflammatory damage in the lungs. Based on the results, F-RUT retained anti-inflammatory activity both in vitro and in vivo in lungs. Compared to the parent compound, F-RUT showed better COX-2 suppression as a COX-2-selective inhibitor with lower cytotoxicity, and enhanced molecular reactivity and biological activity. F-RUT was also observed to reduce reactive oxygen species (ROS) generation and inflammatory infiltrating neutrophils in lipopolysaccharide (LPS)-stimulated zebrafish and ovalbumin (OVA)/alum-challenged KLF-10-knockout mouse lungs, respectively. Furthermore, F-RUT ameliorated the respiratory function in OVA/alum-challenged BALB/c mice by maintaining the thickness of the blood-air barrier in mouse lungs. Overall, these data suggest that F-RUT may function as an effective therapeutic agent for inflammation-induced lung dysfunction, and a better selection for pharmaceutical purposes than conventionally used anti-inflammatory agents.

BackgroundCurrent treatments for osteoporosis are associated with various side effects and do not prevent the age-related decrease in osteoblast number. The objective of this study was to evaluate the effects of iQPR-H2O on osteogenesis.MethodsMouse fibroblast NIH3T3 and pre-osteoblastic MC3T3-E1 cells were cultured in medium prepared with iQPR-H2O or unprocessed mineral water (control cells), and proliferation and differentiation were assessed by MTT and alkaline phosphatase assay, respectively. Mineral deposition by the cells was determined using Alizarin red S staining. A mouse model of osteoporosis, ovariectomized SAMP8 mice, was used to evaluate the effects of iQPR-H2O on osteogenesis in vivo. Mice were given either iQPR-H2O or unprocessed mineral water (control group) for four months after which bone mass density (BMD) measurements were made using a bone densitometer and hematoxylin and eosin staining of bone samples.ResultsNIH3T3 cells grown in medium prepared with iQPR-H2O exhibited significantly greater proliferation. NIH3T3 and MC3T3-E1 cells demonstrated a significant increase in alkaline phosphatase levels in the iQPR-H2O group. MC3T3-E1 cells showed mineralization at day 28. mRNA expression levels of both osteopontin and runt-related transcription factor 2 in MC3T3-E1 cells were higher in the iQPR-H2O group compared with the control group. After four months, significantly greater bone regeneration was evident in ovariectomized SAMP8 mice administered iQPR-H2O as compared with control group.ConclusionsiQPR-H2O may reduce the symptoms of osteoporosis by improving osteogenesis.