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BioMed Research International
Volume 2018, Article ID 3632084, 11 pages
https://doi.org/10.1155/2018/3632084
Research Article

Papain Ameliorates the MPAs Formation-Mediated Activation of Monocytes by Inhibiting Cox-2 Expression via Regulating the MAPKs and PI3K/Akt Signal Pathway

1Center of Laboratory Medicine, Zhejiang Provincial People’s Hospital and People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
2Department of Cardiology, Zhejiang Provincial People’s Hospital and People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
3School of Medicine, Taizhou University, Taizhou 317000, China
4Department of Endocrinology, Zhejiang Provincial People’s Hospital and People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China

Correspondence should be addressed to Xianming Fei; moc.361@ytinutrof

Received 19 May 2018; Revised 29 August 2018; Accepted 25 September 2018; Published 16 October 2018

Academic Editor: Salah Aref

Copyright © 2018 Xianming Fei et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Monocytes activation and subsequent inflammatory response mediated by monocyte-platelet aggregates (MPAs) formation play the key roles in the early pathogenesis of atherosclerosis (AS). Exploration of novel drugs to ameliorate MPAs formation-mediated monocytes activation would be helpful for the treatment of AS patients. Papain has definite pharmacological effects including antiplatelet, thrombolysis, and anti-inflammation. However, its effect on MPAs formation and the following monocytes activation remains vague. This study aimed to illustrate the underlying mechanisms of papain on MPAs formation-initiated monocytes activation in vitro. In this study, Papain, Cox-2 inhibitor (NS-398), and NF-κB agonist (TNF-α) were used as the treating agents, respectively. MPAs formation and activated monocytes were measured by flow cytometry (FCM). Cox-2 mRNA, MCP-1, and proteins of Cox-2 and NF-κB signal pathway were detected by qRT-PCR, ELISA, and western blotting, respectively. As we observed, papain exhibited the powerful inhibitory effects on thrombin-mediated MPAs formation and monocytes activation in a concentration-dependent manner as what Cox-2 inhibitor demonstrated. However, the inhibitory tendency was significantly reversed by TNF-α. We also discovered that both Cox-2 mRNA and protein expression as well as the release of MCP-1 of monocyte was inhibited by either papain or NS-398, but TNF-α stimulated Cox-2 expression and release of MCP-1. The results of western blotting assay indicated that thrombin-mediated proteins expression of MAPKs and PI3K/Akt signal pathway was inhibited by papain and NS-398. However, TNF-α notably abated the inhibitory effects of papain on the process of MPAs-initiated monocytes activation. Our findings suggest that papain can inhibit the MPAs formation-mediated activation of monocytes by inhibiting the MAPKs and PI3K/Akt signal pathway.