Abstract
Echinochrome A (Ech A), a natural pigment extracted from sea urchins, is the active ingredient of a marine-derived pharmaceutical called ‘histochrome’. Since it exhibits several biological activities including anti-oxidative and anti-inflammatory effects, it has been applied to the management of cardiac injury and ocular degenerative disorders in Russia and its protective role has been studied for other pathologic conditions. In the present study, we sought to investigate the therapeutic potential of Ech A for inflammatory bowel disease (IBD) using a murine model of experimental colitis. We found that intravenous injection of Ech A significantly prevented body weight loss and subsequent lethality in colitis-induced mice. Interestingly, T cell proliferation was significantly inhibited upon Ech A treatment in vitro. During the helper T (Th) cell differentiation process, Ech A stimulated the generation regulatory T (Treg) cells that modulate the inflammatory response and immune homeostasis. Moreover, Ech A treatment suppressed the in vitro activation of pro-inflammatory M1 type macrophages, while inducing the production of M2 type macrophages that promote the resolution of inflammation and initiate tissue repair. Based on these results, we suggest that Ech A could provide a beneficial impact on IBD by correcting the imbalance in the intestinal immune system.
Highlights
Echinochrome A (Ech A) is a dark red pigment separated from sea urchin shell and spine and has a chemical structure of 6-ethyl-2,3,5,7,8-pentahydroxy-1,4-naphthoquinone [1,2]
We found that a high dose (10 mg/kg; E10) of Ech A could significantly reduce body weight loss and increase the survival rate of colitis affected mice when compared with vehicle (+) and a low dose of Ech A (1 mg/kg; E1) treated groups (Figure 1A)
H&E staining-based histopathological analysis revealed that typical pathologic signs of the colitis-affected damaged colon such as loss of epithelial structure and irregular morphology of crypts were ameliorated upon the administration of 10 mg/kg Ech A (Figure 1D)
Summary
Echinochrome A (Ech A) is a dark red pigment separated from sea urchin shell and spine and has a chemical structure of 6-ethyl-2,3,5,7,8-pentahydroxy-1,4-naphthoquinone [1,2]. Among the several biological benefits of Ech A, anti-oxidant and anti-inflammatory capacity is proposed as a major underlying therapeutic mechanism. Ech A treatment could reduce ROS production and pro-inflammatory tumor necrosis factor-α (TNF-α) secretion in a rat model of acute uveitis induced by lipopolysaccharide injection [10]. These previous findings imply that Ech A could exert a wide range of therapeutic impacts on other oxidative stress-related and inflammatory pathologic conditions; the cell-type specific regulation of Ech A on the immune system, which consists of various innate and adaptive immune cells, has not been elucidated yet. In vitro results demonstrate that the anti-inflammatory function of Ech A is manifested by, in part, inducing immunomodulatory effector cells, such as M2 macrophages and Treg cells
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