Investigation on the mechanisms of Colquhounia Root Tablets in reversing vascular endothelial cell dysfunction of rheumatoid arthritis via modulating NOD2/SMAD3/VEGFA signaling axis
10.16438/j.0513-4870.2024-0980
- VernacularTitle:火把花根片通过调控NOD2/SMAD3/VEGFA信号通路干预类风湿关节炎血管内皮细胞功能紊乱的作用机制研究
- Author:
Bing-bing CAI
1
;
Ya-wen CHEN
2
;
Tao LI
2
;
Yuan ZENG
2
;
Yan-qiong ZHANG
2
;
Na LIN
2
;
Xia MAO
2
;
Ya LIN
1
Author Information
1. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
- Publication Type:Research Article
- Keywords:
Colquhounia Root Tablets;
rheumatoid arthritis;
angiogenesis;
human umbilical vein endothelial cell;
vascular endothelial cell dysfunction;
pharmacological mechanism
- From:
Acta Pharmaceutica Sinica
2025;60(2):397-407
- CountryChina
- Language:Chinese
-
Abstract:
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.
