期刊
ACS OMEGA
卷 6, 期 50, 页码 34512-34524出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsomega.1c04797
关键词
-
资金
- Jumpcan Pharmaceutical Co., Ltd.
The study confirmed the anti-inflammatory effect of Pudilan antiphlogistic oral liquid (PDL) on various inflammatory models, predicted 45 ingredients interacting with 185 targets, and suggested its involvement in multiple inflammation-related signaling pathways for its anti-inflammatory mechanisms.
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 antiinflammatory 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 via 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 in vivo and in vitro. The results showed that PDL exhibited a proven anti-inflammatory effect on multiple types of inflammatory models, including beta-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-kappa B), and NOD-like receptor (NLR) pathways. Both in vivo and in vitro 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.
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