School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, PR China.
School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, PR China; Shanxi University of Traditional Chinese Medicine, Taiyuan, PR China.
Pharmacol Rep. 2018 Jun;70(3):558-564. doi: 10.1016/j.pharep.2017.12.002. Epub 2017 Dec 15.
Great attention has been paid to the development of novel anti-inflammatory drugs to overcome the adverse reactions of traditional drugs. Recently, a new compound 4-o-methyl-benzenesulfonyl benzoxazolone (MBB) we have prepared attracted our attention for its promising anti-inflammatory activity and low toxicity. The present study aimed to further investigate the anti-inflammatory effects of MBB both in vivo and in vitro in order to determine its potential as a novel NSAIDs lead compound.
The anti-inflammatory effects in vivo were evaluated using acetic acid-induced mice writhing, xylene-induced mice ear edema and collagen-induced rat arthritis. NO, TNF-α, IL-6, IL-1β and iNOS productions by LPS-stimulated RAW264.7 cells were determined to investigate the basis of anti-inflammatory effects. Finally, the COX inhibition effect was tested in vitro using COX inhibitor screening assay kit.
MBB could significantly decrease the writhing and ear swelling in a dose-dependent manner, and it also had a moderate anti-arthritic potential associated with an attenuation of arthritis index score, arthritis swelling, and inhibition of TNF-α and IL-1β. MBB could inhibit the activity of NO, TNF-α, IL-6, IL-1β and iNOS to perform its activity in vitro, but it had no effect against COX-1 and COX-2. The anti-inflammation effect may be mediated via the inhibition of iNOS to reduce the production of inflammatory mediators which should be further confirmed.
The compound MBB displayed anti-inflammatory and anti-arthritic effect, and it could be considered as a new NSAIDs lead compound for the further structure modification to develop novel anti-inflammatory drugs.
为了克服传统药物的不良反应，人们高度关注新型抗炎药物的开发。最近，我们制备的一种新型化合物 4-甲磺酰基苯并噁唑酮（MBB）因其具有良好的抗炎活性和低毒性而引起了我们的关注。本研究旨在进一步研究 MBB 的体内和体外抗炎作用，以确定其作为新型 NSAIDs 先导化合物的潜力。
采用醋酸诱导的小鼠扭体、二甲苯诱导的小鼠耳肿胀和胶原诱导的大鼠关节炎模型评价 MBB 的体内抗炎作用。采用 LPS 刺激 RAW264.7 细胞测定 NO、TNF-α、IL-6、IL-1β 和 iNOS 的产生，以探讨其抗炎作用的机制。最后，采用 COX 抑制剂筛选试剂盒测定 MBB 的体外 COX 抑制作用。
MBB 可显著抑制醋酸诱导的小鼠扭体和二甲苯诱导的小鼠耳肿胀，呈剂量依赖性，且具有中度抗关节炎作用，可降低关节炎指数评分、关节炎肿胀程度，抑制 TNF-α 和 IL-1β 的产生。MBB 可抑制 NO、TNF-α、IL-6、IL-1β 和 iNOS 的活性，发挥其抗炎作用，但对 COX-1 和 COX-2 无作用。抗炎作用可能是通过抑制 iNOS 减少炎症介质的产生来实现的，这需要进一步证实。
化合物 MBB 具有抗炎和抗关节炎作用，可作为新型 NSAIDs 先导化合物，进一步结构修饰开发新型抗炎药物。
