Roflumilast N-oxide is an inhibitor of PDE type 4.

PDE Ⅳ:

Roflumilast N-oxide 以2 nM的剂量在体外WD-HBEC模型中部分缓解了烟草烟雾提取物(CSE)引起的上皮细胞向间充质细胞转变(EMT)。此外，Roflumilast N-oxide (2 nM)能够使经CSE处理后下降的E-钙黏蛋白转录表达量恢复45%。Roflumilast N-oxide (2 nM)还能抑制I型胶原的表达。当细胞与Roflumilast N-oxide (2 nM)共孵育时，上皮细胞表型似乎得到了保护。Roflumilast N-oxide (2 nM)预处理还部分减弱了β-连环蛋白的核内转移。

给db/db小鼠单次注射10 mg/kg 的Roflumilast N-oxide能将血浆中的胰高血糖素样肽-1（GLP-1）增加4倍。通过以3 mg/kg 的剂量对db/db小鼠进行长期治疗，Roflumilast N-oxide展现了对疾病进展的阻止作用。Roflumilast N-oxide能消除血糖增加，将HbA1c的增量减半，并使禁食时血清胰岛素翻倍，与此同时，保持了胰岛形态的完整。此外，Roflumilast N-oxide还能增强初级胰岛中forskolin诱导的胰岛素释放。Roflumilast N-oxide相较其母体化合物表现出更强的降糖效果。

A549 cells are washed and cultured overnight in serum-free F-12 K medium supplemented with antibiotics, L-glutamine and HEPES. The starved cells are incubated with Neutrophil elastase (NE) for 30 min or vehicle (PBS), washed with PBS and then cultured in serum free F-12 K. After stimulation, cell supernatants are collected at 24 h (for cytokine measurements) and cell pellets are collected after 2 h (for mRNA expression analysis). Alternatively, A549 cells are pre-incubated for 2 h with Roflumilast N-oxide (RNO) (at 0.1 μM, 0.3 μM and 1 μM), vehicle (DMSO 0.01%) prior to the addition of NE. All experiments are performed in serum-free medium in triplicate and are repeated at least three times. At the end of the incubation period, culture supernatants are harvested and stored at -80°C until further analysis

At 7 weeks of age, 16 h fasting mice receive a single oral dose of vehicle (4% methocel) or 10 mg/kg Roflumilast-N-oxide, and a glucose bolus of 2 g/kg body weight is co-administered as a physiological initiator for glucagon-like peptide-1 (GLP-1) secretion. Plasma GLP-1 is analyzed 60 min before, and 10 and 60 min after administration of Roflumilast-N-oxide and glucose. The effect of Roflumilast-N-oxide on plasma GLP-1 is also investigated in the absence of the glucose bolus