Oxysophocarpine inhibits airway inflammation and mucus hypersecretion through JNK/AP-1 pathway in vivo and in vitro.

Asthma is a high-incidence disease in the world. Oxysophocarpine (OSC), a quinolizidine alkaloid displays various pharmacological functions including anti-inflammation, neuroprotective, anti-virus and antioxidant. Here, we established mice and cell asthmatic model to explore the effects of OSC for asthma treatment. Mice were sensitized and challenged with ovalbumin (OVA) and treated with OSC before challenge. Enzyme-linked immuno sorbent assay (ELISA), hematoxylin and eosin (H&E), periodic acid-schiff (PAS), tolonium chloride staining and immunohistochemical assay were performed. OSC treatment inhibited inflammatory cell infiltration and mucus secretion in the airway, reduced IgE level in mouse serum and decreased IL-4, IL-5 production in bronchoalveolar lavage fluid (BALF). OSC also reduced the spleen index to regulate immune function. Meanwhile, NCI-H292 cells were induced by lipopolysaccharide (LPS) to simulate airway epithelial injury. OSC pretreatment decreased the IL-6 and IL-8 cytokine levels, mucin 5 AC expression, and mucin 5 AC mRNA level in the cell model. Further, OSC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), and activator protein 1 (AP-1, Fos and Jun). These findings revealed that OSC alleviated bronchial asthma associated with JNK/AP-1 signaling pathway.

Microbiome-metabolome responses of Fuzhuan brick tea crude polysaccharides with immune-protective benefit in cyclophosphamide-induced immunosuppressive mice.

The present study investigated the immune-protective effect of polysaccharides from Fuzhuan brick tea (FBTPs) in cyclophosphamide (Cy)-induced immunosuppressive mice. The results showed that high-dose of FBTPs administration remarkably alleviated Cy-evoked immune damage through improving the body features, organ indices, immune responses and oxidative stress in the mice. Further microbiota analysis revealed that FBTPs obviously restored Cy-evoked microbial dysbiosis by increasing several beneficial bacteria Lactobacillus, Allobaculum, Unclassified_f_Lachnospiraceae and norank_f_Lachnospiraceae, while reducing Bacteroides, norank_f_Ruminococcaceae, Colidextribacter, Alloprevotella, norank_f_Desulfovibrionaceae and Helicobacter. Meanwhile, metabolomics analysis found that FBTPs significantly altered a range of microbial metabolites, including inosine, deoxyinosine, taurine, sinapic acid, maltotriose, butyric acid, lysophosphatidyl cholines (LysoPCs), lysophosphatidic acids (LysoPAs) and choline. These altered metabolites were involved in purine metabolism, ABC transporters, sulfur metabolism, neuroactive ligand-receptor interaction, biosynthesis of phenylpropanoids, carbohydrate digestion and absorption, protein digestion and absorption, choline metabolism in cancer and glycerophospholipid metabolism pathways, which were mainly related to immune responses, antioxidant capacity and energy supply of the immunosuppressive mice. Additionally, some significant correlations were observed between the specific microbiota and effective metabolites. These results provide a novel insight into the immune-protective effect of FBTPs on regulating the intestinal microbiota and metabolism, which are helpful for thoroughly understanding the nutrition of FBTPs and providing a solid basis for the deeper utilization of Fuzhuan brick tea (FBT).