Identification of Pharmacodynamic Material Basis of Ruyi Zhenbaowan by Multidimensional Correlation Model of "Pharmacodynamic-target-component-pharmacokinetic"
10.13422/j.cnki.syfjx.20250261
- VernacularTitle:“药效-靶标-成分-药动”多维关联模式下的如意珍宝丸药效物质基础辨识
- Author:
Mingzhu XU
1
;
Huaiping LI
2
;
Zhaochen MA
3
;
Tao LI
3
;
Yudong LIU
3
;
Ziqing XIAO
3
;
Chu ZHANG
3
;
Kedian CHEN
3
;
Weihua MA
4
;
Feng HUANG
1
;
Na LIN
3
;
Yanqiong ZHANG
1
Author Information
1. College of Traditional Chinese Medicine（TCM）， Yunnan University of Chinese Medicine，Kunming 650500，China
2. Arura Tibetan Medicine Co. Ltd.，Xining 810003，China
3. Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences， Beijing 100700，China
4. Tengzhou TCM Hospital，Tengzhou277500，China
- Publication Type:Journal Article
- Keywords:
Ruyi Zhenbaowan;
neuropathic pain;
material basis of pharmacodynamics;
network pharmacology;
pharmacokinetics;
ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）;
plasma;
cerebrospinal fluid
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(24):68-77
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.
