Rhodiola crenulata reduces ventricular arrhythmia through mitigating the activation of IL-17 and inhibiting the MAPK signaling pathway

• DOI: 10.1007/s10557-020-07072-z
• Publication Date: 2020-09-18T08:03:53Z
• Authors: Ya-Wen Hsiao; Yung-Nan Tsai; Yu-Ting Huang; Shuen-Hsin Liu; Yenn-Jiang Lin; Li-Wei Lo; Yu-Feng Hu; Fa-Po Chung; Shien-Fong Lin; Shih-Lin Chang; Satoshi Higa; Shih-Ann Chen
• Keywords: 0301 basic medicine; Chemokine CCL20; Dose-Response Relationship, Drug; MAP Kinase Signaling System; Interleukin-17; Anti-Inflammatory Agents; Arrhythmias, Cardiac; CD4 Lymphocyte Count; 3. Good health; Disease Models, Animal; Drug Combinations; Electrocardiography; 03 medical and health sciences; Glucosides; Phenols; NLR Family, Pyrin Domain-Containing 3 Protein; Animals; Rhodiola; RNA, Messenger; Rabbits; Inflammation Mediators; Signal Transduction

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.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.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.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.