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Asthma is a heterogeneous clinical syndrome characterized by airway inflammation, hyper-responsiveness and remodeling. Airway remodeling is irreversible by current antiasthmatic drugs, and it is the main cause of severe asthma. Airway smooth muscle cells (ASMCs) act as the main effector cells for airway remodeling; the proliferation and hypertrophy of which are involved in airway remodeling. Caveolin (Cav)− 1 is present on the surface of ASMCs, which is involved in cell cycle and signal transduction regulation, allowing ASMCs to change from proliferation to apoptosis. The extracellular signal-regulated kinase (ERK)1/2 signaling pathway is a common pathway regulated by various proliferative factors, which demonstrates a regulatory role in airway remodeling of asthma. There have been many studies on the correlation between vasoactive intestinal peptide (VIP) and airway reactivity and inflammation in asthma, but the functions and related mechanisms of ASMCs remain unclear. In this study, we established an airway remodeling model in asthmatic mice, and concluded that VIP inhibits airway remodeling in vivo. The in vitro effect of VIP on interleukin-13-induced proliferation of ASMCs was studied by examining the effects of VIP on expression of ERK1/2, phospho-ERK1/2 and Cav-1 in ASMCs, as well as changes in cell cycle distribution. VIP inhibited phosphorylation of the ERK1/2 signaling pathway and expression of Cav-1 on ASMCs and decreased the proportion of S phase cells in the cell cycle, thus inhibiting the proliferation of ASMCs. This study provides a novel therapeutic mechanism for the treatment of asthma. [ABSTRACT FROM AUTHOR]

[Display omitted] • Five new scalarane-type sesterterpenoids were isolated. • The absolute configurations of new structures were assigned by single crystal X-ray diffraction analyses. • Compounds 1 , 2 , 6 , 7 showed inhibitory activities with respective IC 50 values of 16.4, 18.5, 2.6, and 3.7 μ M, on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages. Dysiscalarones A-E (1 – 5), five new scalarane-type bishomoscalarane sesterterpenoids, were isolated from marine sponge Dysidea granulosa collected from the South China Sea, together with two known ones, honulactone A (6) and phyllofolactone I (7). The new structures were determined by extensive spectroscopic analysis including HR-ESI-MS and 1D and 2D NMR data, and their absolute configurations were assigned by single crystal X-ray diffraction analyses. The inhibitory activity of all the seven isolates on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages was evaluated. Of these metabolites, dysiscalarones A-B (1 – 2), honulactone A (6), and phyllofolactone I (7) showed inhibitory activities with respective IC 50 values of 16.4, 18.5, 2.6, and 3.7 μ M, which suggested that the γ -methylated α , β -unsaturated γ -lactone might be the functional group. In addition, all the seven metabolites showed no significant cytotoxicity against lung cancer PC9 cell line at the concentration of 20 μ M. [ABSTRACT FROM AUTHOR]