ARTICLE IN PRESS JID: PHYMED [m5G;December 23, 2015;12:38] Phytomedicine xxx (2015) xxx–xxx Contents lists available at ScienceDirect Phytomedicine journal homepage: www.elsevier.com/locate/phymed Anti-cytokine therapy for prevention of atherosclerosis Tatiana V. Kirichenko a,∗ , Igor A. Sobenin b,c , Dragana Nikolic d , Manfredi Rizzo d,e , Q1 Alexander N. Orekhov a,b a Institute for Atherosclerosis Research, Skolkovo Innovative Center, 4-1-207, Osennaya Str., 121609, Moscow, Russia b Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Str., 125315, Moscow, Russia c Russian Cardiology Research and Production Complex, 15-a 3rd Cherepkovskaya Str., 121552, Moscow, Russia d Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, 141 Via del Vespro, 90127, Palermo, Italy e Euro-Mediterranean Institute of Science and Technology, Via Emerico Amari 123, 90139, Palermo, Italy article info Article history: Received 13 November 2015 Revised 1 December 2015 Accepted 4 December 2015 Available online xxx Keywords: Atherosclerosis prevention Anti-cytokine therapy Inflammation Herbal preparation abstract Background: Currently a chronic inflammation is considered to be the one of the most important reasons of the atherosclerosis progression. A huge amount of researches over the past few decades are devoted to study the various mechanisms of inflammation in the development of atherosclerotic lesions. Purpose: To review current capabilities of anti-inflammatory therapy for the prevention and treatment of atherosclerosis and its clinical manifestations. Methods: Appropriate articles on inflammatory cytokines in atherosclerosis and anti-inflammatory pre- vention of atherosclerosis were searched in PubMed Database from their respective inceptions until Oc- tober 2015. Sections: “The role of inflammatory cytokines in the development of atherosclerotic lesions” describes available data on the possible inflammatory mechanisms of the atherogenesis with a special attention to the role of cytokines. “Modern experience of anti-inflammatory therapy for the treatment of atheroscle- rosis” describes modern anti-inflammatory preparations with anti-atherosclerotic effect including natural preparations. In “the development of anti-inflammatory herbal preparation for atherosclerosis preven- tion” an algorithm is demonstrated that includes screening of anti-cytokine activity of different natural products, the development of the most effective combination and estimation of its effect in cell culture model, in animal model of the acute aseptic inflammation and in a pilot clinical trial. A natural prepa- ration “Inflaminat” based on black elder berries (Sambucus nigra L.), violet tricolor herb (Viola tricolor L.) and calendula flowers (Calendula officinalis L.) possessing anti-cytokine activity was developed using the designed algorithm. The results of the following 2-year double blind placebo-controlled clinical study show that “Inflaminat” reduces carotid IMT progression, i.e. has anti-atherosclerotic effect. Conclusion: Anti-cytokine therapy may be a promising direction in moderation of atherogenesis, espe- cially when it begins on the early stages of subclinical atherosclerosis. The use of herbal preparations with anti-cytokine mechanism of action is the most perspective for timely prevention of atherosclerosis, as they have no significant side effects and can be prescribed for long-term administration. © 2015 Published by Elsevier GmbH. Abbreviations 1 BMI body mass index 2 CRP C-reactive protein 3 ICAM-1 intercellular adhesion molecule 4 IL-1 interleukin 1 5 IL-6 interleukin 6 6 cIMT carotid intima-media thickness 7 LDL low-density lipoproteins 8 ∗ Corresponding author. Tel.: +7 910 4615845; fax: +7 495 4159594. E-mail address: t-gorchakova@mail.ru (T.V. Kirichenko). M-CSF macrophage colony-stimulating factor 9 MCP-1 monocyte chemoattractant protein 1 10 NSAID nonsteroidal anti-inflammatory drug 11 TNF-α tumor necrosis factor α 12 VSMCs vascular smooth muscle cells 13 Introduction 14 Atherosclerosis is a multifactorial disease, and is the ba- Q2 15 sis for stroke, coronary heart disease and myocardial infarc- 16 tion, which remain the leading cause of mortality in Western 17 countries. 18 http://dx.doi.org/10.1016/j.phymed.2015.12.002 0944-7113/© 2015 Published by Elsevier GmbH. Please cite this article as: T.V. Kirichenko et al., Anti-cytokine therapy for prevention of atherosclerosis, Phytomedicine (2015), http://dx.doi.org/10.1016/j.phymed.2015.12.002