中药药理与临床2025,Vol.41Issue(5):2-8,7.
疮灵液调控PI3K/AKT/NF-κB信号通路促进创面愈合
Chuangling Liquid Promotes Wound Healing by Regulating the PI3K-Akt/NF-κB Signaling Pathway
摘要
Abstract
Objective:To identify the chemical constituents of Chuangling(疮灵)Liquid by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)and explore the mechanism of Chuangling Liquid in promoting wound healing by animal experiments.Methods:The active components of Chuangling Liquid were identified by UPLC-Q-TOF-MS/MS.Net-work pharmacology was employed to predict the targets of Chuangling Liquid in promoting wound healing.Gene ontology and Kyoto Encyclo-pedia of Genes and Genomes pathway enrichment analyzes were performed on these targets.A rat model of acute full-thickness skin defect was established and treated with Chuangling Liquid,after which the wound healing was observed.Hematoxylin-eosin staining and Masson staining were performed to reveal the pathological conditions of the skin.The enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),transforming growth factor-β(TGF-β),vascular endothelial growth factor(VEGF)in the serum,as well as hydroxyproline(HYP)in the skin tissue.Western blot was employed to determine the protein levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated(p)-PI3K,protein kinase B(AKT),p-AKT,nuclear factor-kappa B(NF-κB),and IL-1β in the wound tissue of rats.Results:A total of 67 compounds were identified in Chuangling Liquid.Network pharmacology analysis screened out 34 core targets,including TP53,TNF,AKT1,EGFR,PIK3R1,and IL-1β.These targets were involved in 159 inflammation-asso-ciated pathways,such as PI3K/Akt,mitogen-activated protein kinase(MAPK),NF-κB,TNF,and Th17 signaling pathways.Molecular doc-king demonstrated that active components,including myricetin,chrysophanol,rhein,quercetin,and hyperoside,exhibited strong binding affinity with TNF,AKT1,EGFR,and IL-1β.Animal experiment results showed that compared with the normal control group,the model control group demonstrated intensified inflammatory cell infiltration,reduced collagen fiber deposition,decreased HYP content in the skin tissue(P<0.01),elevated serum levels of IL-1β,TNF-α,and TGF-β(P<0.01),declined VEGF level(P<0.01),and down-regulated protein levels of p-PI3K and p-AKT(P<0.01).Compared with the model control group,Chuangling Liquid at different doses increased the wound healing rate,decreased inflammatory cell infiltration,and increased collagen fiber deposition and the HYP content in the skin tissue(P<0.05).Ad-ditionally,Chuangling Liquid administrated at 0.45 g/mL and 0.90 g/mL lowered the serum levels of IL-1β and TNF-α(P<0.01),raised the VEGF and TGF-β levels(P<0.01),up-regulated the protein levels of p-PI3K and p-AKT(P<0.05 or P<0.01),and down-regulated the protein level of IL-1β(P<0.05 or P<0.01)in the skin tissue.Conclusion:Chuangling Liquid regulates the PI3K/Akt/NF-κB pathway to inhibit inflammation and promote angiogenesis,thereby facilitating wound healing.关键词
疮灵液/超高效液相色谱-四极杆飞行时间质谱联用技术/网络药理学/创面愈合/核因子-κB/磷脂酰肌醇-3激酶/蛋白激酶/丝裂原活化蛋白激酶Key words
Chuangling Liquid/UPLC-Q-TOF-MS/Network pharmacology/Wound healing/Nuclear factor-kappa B(NF-κB)/Phosphatidyli-nositol 3-kinase(PI3K)/Protein kinase B(AKT)/Mitogen-activated protein kinase(MAPK)引用本文复制引用
蒋晓涵,王雅宏,王晨,李佳璇,王富江,葛海涛..疮灵液调控PI3K/AKT/NF-κB信号通路促进创面愈合[J].中药药理与临床,2025,41(5):2-8,7.基金项目
泰州市"凤城英才计划"青年科技人才托举工程(编号:TZ-018). (编号:TZ-018)