Pharmacodynamics study and establishment of a PK-PD model for Epimedii Folium-Chuanxiong Rhizoma in treating osteoarthritis in rats.
10.19540/j.cnki.cjcmm.20241108.201
- Author:
En-Hui WU
1
;
Jian-Hua ZHANG
2
;
Wen-Jun CHEN
1
;
Ya-Hong WANG
1
;
Hua YIN
1
Author Information
1. Research Laboratory for Standardization of Chinese Medicines, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University Hangzhou 311402, China.
2. Department of Osteopathy and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou 310006, China.
- Publication Type:Journal Article
- Keywords:
Epimedii Folium-Chuanxiong Rhizoma;
osteoarthritis;
pharmacodynamic material basis;
pharmacokinetic-pharmacodynamic model
- MeSH:
Animals;
Rats;
Drugs, Chinese Herbal/pharmacology*;
Male;
Rats, Sprague-Dawley;
Osteoarthritis/metabolism*;
Epimedium/chemistry*;
Interleukin-1beta/blood*;
Tumor Necrosis Factor-alpha/blood*;
Disease Models, Animal;
Nitric Oxide/blood*;
Humans;
Rhizome/chemistry*
- From:
China Journal of Chinese Materia Medica
2025;50(5):1377-1384
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to reveal the correlation between the pharmacokinetics(PK) and pharmacodynamics(PD) of multiple components in Epimedii Folium-Chuanxiong Rhizoma and clarify the pharmacodynamic material basis and mechanism of this herb pair in treating osteoarthritis. The Hulth method was used to establish the rat model of osteoarthritis and plasma was collected at various time points after drug administration. The plasma concentrations of multiple components were measured. Enzyme-linked immunosorbent assay(ELISA) was used to measure the plasma concentrations of matrix metalloproteinase(MMP)-3, MMP-13, interleukin-1β(IL-1β), nitric oxide(NO), and tumor necrosis factor-α(TNF-α) as pharmacodynamic indicators. Self-defined weighting coefficients were used to calculate the PK and PD data, and a Sigmoid E_(max) fitting model was used to evaluate the synergistic effect of the compatibility of Epimedii Folium-Chuanxiong Rhizoma. The PK-PD models for Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma were E=(1.926×C~(2.652))/(0.136 6~(2.652)+C~(2.652)), E=(1.618×C~(345.2))/(0.118 4~(345.2)+C~(345.2)), and E=(2.305×C~(2.786))/(0.240 3~(2.786)+C~(2.786)), respectively. The E_(max) of Epimedii Folium-Chuanxiong Rhizoma was larger than those of the two herbal medicines alone. The EC_(50) of the herb pair was lower than the sum of Epimedii Folium and Chuanxiong Rhizoma alone. The concentrations of MMP-3, MMP-13, IL-1β, NO, and TNF-α were correlated with mass concentrations of multiple components in Epimedii Folium and Chuanxiong Rhizoma, and the compatibility was better than single use. Epimedii Folium, Chuanxiong Rhizoma, and Epimedii Folium-Chuanxiong Rhizoma may play a role in the treatment of osteoarthritis by inhibiting MMP-3, MMP-13, IL-1β, NO, and TNF-α.
