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- Title
Rhodiola crenulata reduces ventricular arrhythmia through mitigating the activation of IL-17 and inhibiting the MAPK signaling pathway.
- Authors
Hsiao, Ya-Wen; Tsai, Yung-Nan; Huang, Yu-Ting; Liu, Shuen-Hsin; Lin, Yenn-Jiang; Lo, Li-Wei; Hu, Yu-Feng; Chung, Fa-Po; Lin, Shien-Fong; Chang, Shih-Lin; Higa, Satoshi; Chen, Shih-Ann
- Abstract
Purpose: Ventricular arrhythmia (VA) is related to inflammatory activity. Rhodiola crenulate (RC) and its main active component, salidroside, have been reported as anti-inflammatory agents. The aim of this study was to demonstrate the effect of RC and salidroside in preventing VA via the inhibition of IL-17 in an ischemic heart failure (HF) model. Methods: Rabbit HF models were established by coronary artery ligation for 4 weeks. These rabbits were treated with RC (125, 250, 500 mg/kg) and salidroside (9.5 mg/kg) once every 2 days for 4 weeks. WBC, serum biochemistry, ECG, and the expression of CD4+ T cells were measured every 2 weeks. The mRNA and protein expressions of IL-17 were measured by real time-PCR, ELISA, and Western blotting after RC and salidroside treatment for 4 weeks. Open-chest epicardial catheter stimulation was performed for VA provocation. Results: After RC and salidroside treatment in HF left ventricle, (1) the levels of WBC and CD4+ T cells decreased, (2) the expression of IL-17 and its downstream target genes, IL-6, TNF-α, IL-1β, IL-8, and CCL20, reduced, (3) the level of NLRP3 inflammasome was decreased, (4) fibrosis and collagen production were significantly downregulated, (5) p38 MAPK and ERK1/2 phosphorylation were attenuated, (6) the inducibility of VA was decreased, and (7) the levels of Kir2.1, Nav1.5, NCX, PLB, SERCA2a and RyR were up-regulated. Conclusions: RC inhibited the expression of IL-17 and its downstream target genes that were mediated by activation of several MAPKs, which decreased the levels of fibrosis and apoptosis and suppressed VA.
- Subjects
VENTRICULAR arrhythmia; INTERLEUKIN-17; CELLULAR signal transduction; GENE expression; MITOGEN-activated protein kinases; NLRP3 protein
- Publication
Cardiovascular Drugs & Therapy, 2021, Vol 35, Issue 5, p889
- ISSN
0920-3206
- Publication type
Article
- DOI
10.1007/s10557-020-07072-z