rhPLD2 inhibits airway inflammation in an asthmatic murine model through induction of stable CD25+ Foxp3+ Tregs.

Our previous studies have shown that recombinant human phospholipase D2 (rhPLD2) plays a modulator role on NF-κB and PKC signaling pathways. It also inhibits IL-5-induced inflammatory response in chronic asthmatic guinea pigs. Additionally, increasing evidence also has revealed that the adoptive transfer of induced regulatory T cells (Tregs) may be a therapeutic solution to airway allergic diseases. To investigate the epigenetic, transcriptomic and phenotypic variability of Treg population in an ovalbumin (OVA)-induced airway inflammation model derived from the induction of rhPLD2, OVA-induced asthmatic murine model is used in this study. The lung inflammation, eosinophil infiltration, the differentiation and proliferation of T helper cells and the amplification of Tregs were examined in this mouse model with and without rhPLD2 induction. Our data showed that rhPLD2 administration in asthmatic mice significantly increases CD4+CD25+ Foxp3+ Treg cell numbers and alleviates lung inflammation. The addition of rhPLD2 in vitro enhanced the demethylation of Treg-specificdemethylated region (TSDR) in iTregs, suggesting that rhPLD2 protein may be involved in improving the quality and quantity of Treg cells that eventually significantly reduces lung inflammation in asthmatic murine model. These results suggest that rhPLD2 could have a clinical impact treating patients with allergic airway inflammation via promoting and stabilizing iTreg differentiation and function.

Synthesis and biological evaluation of novel ursolic acid analogues as potential α-glucosidase inhibitors.

Ursolic acid (UA) is a major pentacyclic triterpenoid in plants, vegetables and fruits, which has been reported to have a potential anti-diabetic activity. Despite various semi-synthetic ursolic acid derivatives already described, new derivatives still need to be designed and synthesized to further improve the anti-diabetic activity. In the present study, two series of novel UA derivatives, were synthesized and their structures were confirmed. The enzyme inhibition activities of semi-synthesized analogues against α-glucosidase were screened in vitro. The results indicated that most of UA derivatives showed a significant inhibitory activity, especially analogues UA-O-i with the IC50 values of 0.71 ± 0.27 µM, which was more potential than other analogues and the positive control. Furthermore, molecular docking studies were also investigated to verify the in vitro study. Structure modification at the C-3 and C-2 positions of UA was an effective approach to obtain the desired ligand from UA, whose structure was in accordance with the active pocket. Besides, suitable hydrophobic group at the position of C-2 might play an important role for the docking selectivity and binding affinity between the ligand and the homology modelling protein. These results could be helpful for designing more potential α-glucosidase inhibitors from UA in the future.