Mechanism of Astragali Radix in treatment of knee osteoarthritis based on GLP-1/GLP-1R axis.
10.19540/j.cnki.cjcmm.20240611.709
- Author:
Jia CHEN
1
;
Jian-Guo WANG
2
;
Gui-Yu WANG
1
;
Jing-Ruo WU
1
;
Jin-Ru YUE
1
;
Qi LIU
1
;
Jing-Shu LIU
1
Author Information
1. College of Basic Medical Sciences, Shanxi University of Chinese Medicine Jinzhong 030600, China.
2. Shanxi Provincial Integrated Traditional Chinese Medicine and Western Medicine Hospital Taiyuan 030000, China.
- Publication Type:Journal Article
- Keywords:
Astragali Radix;
GLP-1/GLP-1R axis;
cartilage protection;
knee osteoarthritis
- MeSH:
Animals;
Male;
Rats, Sprague-Dawley;
Osteoarthritis, Knee/genetics*;
Rats;
Drugs, Chinese Herbal/pharmacology*;
Glucagon-Like Peptide 1/metabolism*;
Glucagon-Like Peptide-1 Receptor/metabolism*;
Astragalus propinquus/chemistry*;
Humans;
Matrix Metalloproteinase 13/metabolism*;
Signal Transduction/drug effects*;
Tumor Necrosis Factor-alpha/metabolism*;
Astragalus Plant/chemistry*;
Apoptosis/drug effects*
- From:
China Journal of Chinese Materia Medica
2024;49(22):6190-6197
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to observe the effects of different doses of Astragali Radix on the expression of glucagon(GLP-1) in se-rum and glucagon receptor(GLP-1R) in cartilage tissue in rats with knee osteoarthritis(KOA), explore the effect of Astragali Radix on the inflammation and apoptosis of KOA by regulating GLP-1/GLP-1R signaling axis, and investigate the mechanism of its action in alleviating KOA. Forty-eight male SD rats were randomly divided into six groups: blank group, model group, low-, medium-, and high-dose Astragali Radix groups(3.125, 6.25, and 12.5 g·kg~(-1)), and glucosamine sulfate group(0.1 g·kg~(-1)). Except for the blank group, rats in other groups were injected with sodium iodoacetate(MIA) into the knee joint to establish KOA models. After successful modeling, the rats were continuously treated for five weeks. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of GLP-1, tumor necrosis factor-alpha(TNF-α), and interleukin-1β(IL-1β) in rat serum. Pathological examination was utilized to observe the pathological changes in knee joint cartilage. The mRNA levels of TNF-α and MMP13 in knee joint cartilage were detected by qRT-PCR, and the protein expression levels of GLP-1R, MMP13, and caspase-8 in knee joint cartilage were detected by Western blot. The expression of GLP-1R and MMP13 in the knee joint was detected by immunohistochemistry. Tunel staining was used to observe the apoptosis of chondrocytes in the knee joint. The above experimental results showed that Astragali Radix may raise the serum levels of GLP-1, reduce serum levels of TNF-α and IL-1, and decrease the relative mRNA expression of TNF-α and MMP13 through the GLP-1/GLP-1R axis. It thus activated GLP-1R, reduced the protein expression of MMP13 and caspase-8 in cartilage, and regulated their related signaling pathways to improve inflammation and apoptosis, so as to protect cartilage and improve KOA.