Colchicine: A Promising Drug in Clinical Translation, A Minireview Focused on Cardiovascular Diseases

Abstract

Colchicine is a venerable drug used for centuries for rheumatic diseases with potential pleiotropic anti-inflammatory effects. One of the main concerns remains the tolerability especially digestive side effects, but this aspect has been improved by many pharmacological improvements. Nowadays, colchine is a promising drug for cancer therapy and cardiovascular diseases with several studies currently going on, an improved therapeutic window and a wider range of translations in cardioprotection but also in atrial fibrillation, ischemic cardiopathy or pericarditis. COLCHICINE IS A VENERABLE DRUGColchicine has been used for centuries for the treatment and prevention of gouty attacks and rheumatic complaints and is one of the oldest drugs still currently available as recently reviewed [1] .The active compound was initially extracted from the plant autumn crocus [2] but the active chemical compound was isolated only in 1820 [3] . In 1889, a large dose of tincture of Colchicum was injected in two dogs leading to the observation that anatelophases was blocked during mitosis and providing the first cellular explanation of the activity of the "poison-drug" [4] : this is functioning as a mitotic spindle poison. The structure of the active compound was elucidated only in 1955. Colchicine exerts its well-known effects including anti-cancer ones, first by blocking the tubules in the cell (spindle poison) [1] . Secondly, it could exert pleiotropic anti-inflammatory effects. Colchicine could have also direct anti-inflammatory effects (reviewed in [5] ) by inhibiting key inflammatory signaling networks known as the inflammasome and proinflammatory cytokines. The crystals involved in the pathogeny of gout and chondrocalcinosis have been shown to engage the caspase-1-activating NALP3 inflammasome [6] , resulting in the production of active interleukin-1β (IL-1β) and IL-18. Moreover, impaired neutrophil influx is observed in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or IL-1β-receptor-deficient mice [6] . Although the most important effect of colchicine in gouty inflammation is inhibition of neutrophil migration [7] , these data suggest an alternative mechanism for the effectiveness of colchicine through anti-inflammatory functions,