*Article* **Echinochrome A Reduces Colitis in Mice and Induces In Vitro Generation of Regulatory Immune Cells**

**Su-Jeong Oh 1,**†**, Yoojin Seo 2,**†**, Ji-Su Ahn 1, Ye Young Shin 1, Ji Won Yang 2, Hyoung Kyu Kim 3, Jin Han 3, Natalia P. Mishchenko 4, Sergey A. Fedoreyev 4, Valentin A. Stonik <sup>4</sup> and Hyung-Sik Kim 1,2,\***


Received: 31 August 2019; Accepted: 26 October 2019; Published: 31 October 2019

**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.

**Keywords:** echinochrome A; marine drugs; inflammatory bowel disease; regulatory T cells; macrophages
