PURPOSE: Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma. METHODS: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro. RESULTS: We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells. CONCLUSIONS: These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma.
Animals ; Asthma* ; Bronchoalveolar Lavage Fluid ; Cell Adhesion Molecules ; Chemokines ; Cholesterol ; Cytokines ; Eosinophils ; Epithelial Cells ; Female ; Gene Expression ; Goblet Cells ; HL-60 Cells ; Humans ; Hyperplasia ; Immunoglobulin E ; Inflammation* ; Injections, Intraperitoneal ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Lovastatin* ; Lung ; Mice ; Mucin 5AC ; Mucus* ; Ovalbumin ; Ovum ; Real-Time Polymerase Chain Reaction

Objective To develop a method of isolation and identification of exosomes of bone marrow mesenchymal stem cells.Methods The mesenchymal stem cells were cultured by whole bone marrow adherence method.A new reagent -exosomes extraction kit was used to isolate and collecte exosomes.The exosomes were identified by elec-tron microscopy,particle size detection,flow cytometry and Western blot.Results The expression of CD45 on the surface of the third generation bone marrow mesenchymal stem cells was negative,and CD73 and CD105 were posi-tive;exosomes derived from bone marrow mesenchymal stem cells were round or oval,the size is non-uniform,the diameter is 30~100 nm,have a complete membrane structure,and containing low-density substances;Particle size detection particle diameter of the main peak was 61.25 nm, in which the diameter of particles was about 20-200 nm accounted for 72.4%;exosome expressed CD63 and CD81;The expression of CD9 and CD63 from cell cul-ture supernatants was positive.Conclusions The exosomes can be collected in the medium of mesenchymal stem cells.The exosomes derived from bone marrow mesenchymal stem cells can be identified by electron microscopy, particle size detection,flow cytometry and Western blot.

Mangosteen (Garcinia mangostana Linn.) is a well-known tropical tree indigenous to Southeast Asia. Its fruit's pericarp abounds with a class of isoprenylated xanthones which are referred as mangostins. Numerous in vitro and in vivo studies have shown that mangostins and their derivatives possess diverse pharmacological activities, such as antibacterial, antifungal, antimalarial, anticarcinogenic, antiatherogenic activities as well as neuroprotective properties in Alzheimer's disease (AD). This review article provides a comprehensive review of the pharmacological activities of mangostins and their derivatives to reveal their promising utilities in the treatment of certain important diseases, mainly focusing on the discussions of the underlying molecular targets/pathways, modes of action, and relevant structure-activity relationships (SARs). Meanwhile, the pharmacokinetics (PK) profile and recent toxicological studies of mangostins are also described for further druggability exploration in the future.
Animals ; Anti-Infective Agents ; pharmacology ; Anticarcinogenic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Antioxidants ; pharmacology ; Cardiovascular Agents ; pharmacology ; Fruit ; chemistry ; Garcinia mangostana ; chemistry ; Humans ; Neuroprotective Agents ; pharmacology ; Phytotherapy ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Xanthones ; pharmacology