Tian Gang, Gu Xiaoqun, Bao Kaifan, Yu Xuerui, Zhang Yuheng, Xu Yifan, Zheng Jie, Hong Min
Jumpcan Pharmaceutical Co., Ltd, Taixing 225441, China.
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
ACS Omega. 2021 Dec 9;6(50):34512-34524. doi: 10.1021/acsomega.1c04797. eCollection 2021 Dec 21.
Pudilan antiphlogistic oral liquid (PDL) is a commercial traditional Chinese medicine widely used in the treatment of a variety of inflammatory diseases. However, the specific mechanisms of PDL's anti-inflammatory effects have not been fully understood. In this research, five classic inflammatory models and a network pharmacology-based strategy were utilized to evaluate its anti-inflammatory efficacy and elucidate its multicomponent and multitarget mode of the anti-inflammatory mechanism. A systems pharmacology approach was carried out a holistic process of active compound screening, target acquisition, network construction, and further analysis. The potential component-target-associated anti-inflammatory mechanisms of PDL were further verified both and . The results showed that PDL exhibited a proven anti-inflammatory effect on multiple types of inflammatory models, including β-hemolytic streptococcus-induced acute pharyngitis, LPS-induced acute lung injury, xylene-induced ear swelling, carrageenan-induced paw edema, and acetic acid-induced capillary permeability-increasing models. Systems pharmacology analysis predicted 45 ingredients of PDL that interact with 185 targets, of which 38 overlapped with the inflammation-related targets. Furthermore, KEGG pathway analysis showed that the predicted targets were mainly involved in hypoxia-inducible factor (HIF)-1, tumor necrosis factor (TNF), nuclear factor kappa-B (NF-κB), and NOD-like receptor (NLR) pathways. Both and experiments clarified that PDL has anti-inflammatory potency by inhibiting PI3K and p38 phosphorylation and activating the NLRP3 inflammasome. Our results suggested that PDL has an efficient and extensive anti-inflammatory effect, and its anti-inflammatory mechanisms may involve multiple inflammatory-associated signaling pathways, including HIF-1- and TNF-mediated pathways and NLRP3 inflammasome activation.
蒲地蓝消炎口服液(PDL)是一种广泛用于治疗多种炎症性疾病的商业中药。然而,PDL抗炎作用的具体机制尚未完全明确。在本研究中,利用五种经典炎症模型和基于网络药理学的策略来评估其抗炎功效,并阐明其抗炎机制的多成分、多靶点模式。开展了系统药理学方法,这是一个包括活性化合物筛选、靶点获取、网络构建及进一步分析的整体过程。PDL潜在的成分-靶点相关抗炎机制在体内和体外均得到进一步验证。结果表明,PDL对多种炎症模型均表现出确切的抗炎作用,包括β-溶血性链球菌诱导的急性咽炎、脂多糖诱导的急性肺损伤、二甲苯诱导的耳肿胀、角叉菜胶诱导的足爪水肿以及醋酸诱导的毛细血管通透性增加模型。系统药理学分析预测出PDL的45种成分与185个靶点相互作用,其中38个与炎症相关靶点重叠。此外,KEGG通路分析表明,预测的靶点主要涉及缺氧诱导因子(HIF)-1、肿瘤坏死因子(TNF)、核因子κB(NF-κB)和NOD样受体(NLR)通路。体内和体外实验均阐明,PDL通过抑制PI3K和p38磷酸化并激活NLRP3炎性小体而具有抗炎效力。我们的结果表明,PDL具有高效且广泛的抗炎作用,其抗炎机制可能涉及多种炎症相关信号通路,包括HIF-1和TNF介导的通路以及NLRP3炎性小体激活。