摘要
目的:探讨消定膏中主要透皮成分的体外释放率和经皮渗透动力学,并对消定膏中透皮成分治疗骨关节炎的作用机制进行研究。方法:以治疗骨关节炎的传统外用膏剂消定膏为研究对象,选用改良版Franz透皮扩散池,分别以透析膜及离体大鼠腹部皮肤为透皮材料,PEG400-95%乙醇-生理盐水(1∶3∶6)为接收液,采用HPLC法同时测定接收液中儿茶素、表儿茶素、芦荟大黄素、大黄酚、大黄酸5种成分的含量,计算24 h内消定膏主要透皮成分的累计释放量,绘制24 h内累计释放率曲线,拟合动力学方程;应用网络药理学方法筛选核心靶点,构建消定膏“透皮成分-疾病-靶点”网络,进行GO和KEGG富集分析,预测消定膏治疗骨关节炎的作用机制。结果:消定膏中儿茶素、表儿茶素、芦荟大黄素、大黄酚、大黄酸体外释放和透皮吸收行为中的单位面积累计释放量随着时间增加而增加,动力学拟合方程符合一级方程和Higuchi方程。网络药理学结果显示,消定膏中透皮成分作用TP53、STAT3、RELA、MAPK1、MAPK3、PIK3R1、JUN、AKT1、TNF等核心靶点,通过调控TNF、AGE-RAGE、HIF-1、IL-17等信号通路发挥抗炎、镇痛等作用。结论:消定膏具有良好的释放度和透皮性能,具有长效缓释的特点,初步揭示了消定膏透皮成分治疗骨关节炎的作用靶点和作用机制,为消定膏药效物质基础研究提供参考依据。
Objective:To investigate the in vitro released rate and transdermal permeation kinetics of the main transdermal components in Xiaoding ointment,and to study the mechanism of transdermal components in Xiaoding ointment in treating Osteoarthritis.Methods:Taking Xiaoding ointment,a traditional external ointment for the treatment of osteoarthritis,as the research object.A modified version of Franz's transdermal diffusion cell was selected,and PEG400-95%ethanol-saline(1∶3∶6)was used as the receiving solution with dialysis membrane and isolated rat abdominal skin as the transdermal materials,and the contents of Catechin,Epicatechin,Aloe emodin,Rhein and Chrysophanic in the receiving solution were determined by HPLC.The cumulative release of the main transdermal components in Xiaoding ointment was calculated over 24 h.The cumulative release rate curves were plotted over 24 h,and the kinetic equations were fitted.Using the network pharmacology method to screen the core targets,conduct GO and KEGG enrichment analysis,and construct the network of“Xiaoding ointment-transdermal component-target-pathway-Osteoarthritis”to predict the mechanism of action of elimination cream in the treatment of Osteoarthritis.Results:The cumulative release per unit area of Catechin,Epicatechin,Aloeemodin,Rhein and Chrysophanic in vitro release and transdermal absorption behavior in Xiaoding ointment increased with time,and the kinetic fitting equations were in accordance with the first-order equation and Higuchi equation.The results of network pharmacology show that the transdermal components in Xiaoding ointment act on TP53,STAT3,RELA,MAPK1,MAPK3,PIK3R1,JUN,AKT1,TNF and other core targets,and exert anti-inflammatory and analgesic effects by regulating TNF,AGE-RAGE,HIF-1,IL-17 and other signaling pathways.Conclusion:Xiaoding ointment has good release and transdermal properties,and has the characteristics of long-term sustained release.Preliminarily reveal the target and mechanism of action of the transdermal components of Xiaoding ointm
作者
周洁
靳子明
周晶晶
李倩
张岩
窦霞
Zhou Jie;Jin Ziming;Zhou Jingjing;Li Qian;Zhang Yan;Dou Xia(School of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730030,China;Preparation Center,The Hospital Affiliated to Gansu University of Chinese Medicine,Lanzhou 730099,China;Yang Xicang National Famous Old Chinese Medicine Experts Workshop,Lanzhou 730099,China)
出处
《亚太传统医药》
2024年第7期24-31,共8页
Asia-Pacific Traditional Medicine
基金
国家自然科学基金(82360944)
兰州市人才创新创业项目(2021-RC-104)
甘肃省中医药管理局中医药重大项目(GZKZ-2021-5)。
关键词
消定膏
体外释放
透皮吸收
网络药理学
Xiaoding Ointment
In Vitro Release
Transdermal Absorption
Network Pharmacology
