Mechanism of kaempferol on intervertebral disc degeneration based on p38 MAPK signaling pathway.
10.19540/j.cnki.cjcmm.20240625.401
- Author:
Chen-Mo-Ji WANG
1
;
Ya-Dong WU
2
;
Song-Lin LIANG
1
;
Shang GAO
1
;
Ze-Lin YUE
1
;
Lu-Ming KONG
1
;
Kuan-Hui GAO
1
;
Nian-Hu LI
3
Author Information
1. the First Clinical Medical College of Shandong University of Traditional Chinese Medicine Ji'nan 250014, China.
2. the First Clinical Medical College of Shandong University of Traditional Chinese Medicine Ji'nan 250014, China Rizhao City Hospital of Traditional Chinese Medicine Rizhao 276800, China.
3. Affiliated Hospital of Shandong University of Traditional Chinese Medicine Ji'nan 250014, China.
- Publication Type:Journal Article
- Keywords:
intervertebral disc;
intervertebral disc degeneration;
kaempferol;
nucleus pulposus cells;
p38 MAPK signaling pathway
- MeSH:
Animals;
p38 Mitogen-Activated Protein Kinases/genetics*;
Kaempferols/pharmacology*;
Intervertebral Disc Degeneration/genetics*;
Rats;
Rats, Sprague-Dawley;
Male;
Apoptosis/drug effects*;
Cell Proliferation/drug effects*;
Nucleus Pulposus/drug effects*;
Signal Transduction/drug effects*;
Humans;
MAP Kinase Signaling System/drug effects*
- From:
China Journal of Chinese Materia Medica
2024;49(21):5721-5729
- CountryChina
- Language:Chinese
-
Abstract:
This study investigated the mechanism by which kaempferol(KAE) affected intervertebral disc degeneration(IDD) through the p38 mitogen-activated protein kinase(p38 MAPK) signaling pathway. Rats were randomly divided into five groups: control group, model group, low-dose KAE group, medium-dose KAE group, and high-dose KAE group. An IDD model was established by needle puncture of the caudal intervertebral discs. Four weeks post-surgery, the rats were administered KAE via gavage for 8 consecutive weeks. Magnetic resonance imaging(MRI) was performed, and samples were collected. In vitro, an inflammation model of nucleus pulposus cells(NPCs) induced by tumor necrosis factor-alpha(TNF-α) was constructed. Anisomycin was used to activate the p38 MAPK signaling pathway. NPCs were divided into blank, model, KAE, agonist, and KAE + agonist groups. After 1 day of treatment, cell proliferation activity was assessed using the CCK-8. Protein expression levels were determined by Western blot, and mRNA expression was measured by real-time quantitative polymerase chain reaction. Cell apoptosis was detected by TUNEL staining, and immunofluorescence staining was used to detect type Ⅱ collagen and matrix metalloproteinase 3(MMP3). In vivo results indicated significant improvement in the degree of IDD in the treatment groups compared to the model group, with the medium-dose group showing more pronounced therapeutic effects than the low-and high-dose groups. In vitro results demonstrated that KAE treatment significantly enhanced NPC proliferation activity, down-regulated the expression levels of Bcl-2-associated X protein(Bax), interleukin-6(IL-6), interleukin-17A(IL-17A), MMP3, and a disintegrin and metalloproteinase with thrombospondin motifs 5, and inhibited the phosphorylation of p38 MAPK pathway-related proteins. Activation of the p38 MAPK signaling pathway by anisomycin reduced the therapeutic effects of KAE. The study concluded that KAE could improve the proliferation activity of degenerated NPCs, reduce inflammation levels, and slow the progression of IDD in rats, and the mechanism was likely related to the regulation of the p38 MAPK signaling pathway.
