Activity of Codonopsis canescens against rheumatoid arthritis based on TLRs/MAPKs/NF-κB signaling pathways and its mechanism.
10.19540/j.cnki.cjcmm.20220727.401
- Author:
Yu-Jie WANG
1
;
Xiao-Yu ZHONG
2
;
Xin-Hong WANG
1
;
Yuan-Han ZHONG
1
;
Lin LIU
1
;
Fang-Yuan LIU
1
;
Jin-Xiang ZENG
1
;
Ji-Xiao ZHU
1
;
Xiao-Lang DU
1
;
Min LI
1
;
Gang REN
1
;
Guo-Yue ZHONG
1
;
Xiao-Min WANG
3
Author Information
1. Research Center of Chinese Medicine Resource and National Medicine,Jiangxi University of Chinese Medicine Nanchang 330004,China.
2. School of Pharmacy,Jiangxi University of Chinese Medicine Nanchang 330004,China.
3. School of Chinese Medicines and Life Science,Jiangxi University of Chinese Medicine Nanchang 330004,China.
- Publication Type:Journal Article
- Keywords:
Codonopsis canescens;
TLRs/MAPKs/NF-κB signaling pathway;
UPLC-Q-TOF-MS;
activity and mechanism;
rheumatoid arthritis
- MeSH:
Animals;
Cattle;
Male;
Rats;
Arthritis, Experimental/drug therapy*;
Arthritis, Rheumatoid/drug therapy*;
Body Weight;
Codonopsis/chemistry*;
Interleukin-6/blood*;
NF-kappa B/genetics*;
p38 Mitogen-Activated Protein Kinases/metabolism*;
Plant Extracts/therapeutic use*;
Rats, Sprague-Dawley;
Signal Transduction;
Toll-Like Receptor 2/metabolism*;
Toll-Like Receptor 4/metabolism*;
Tumor Necrosis Factor-alpha/pharmacology*
- From:
China Journal of Chinese Materia Medica
2022;47(22):6164-6174
- CountryChina
- Language:Chinese
-
Abstract:
This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
