Implication of Echinochrome A in the Plasticity and Damage of Intestinal Epithelium

Abstract

The diverse therapeutic feasibility of the sea urchin-derived naphthoquinone pigment, Echinochrome A (Ech A), has been studied. Simple and noninvasive administration routes should be explored, to obtain the feasibility. Although the therapeutic potential has been proven through several preclinical studies, the biosafety of orally administered Ech A and its direct influence on intestinal cells have not been evaluated. To estimate the bioavailability of Ech A as an oral administration drug, small intestinal and colonic epithelial organoids were developed from mice and humans. The morphology and cellular composition of intestinal organoids were evaluated after Ech A treatment. Ech A treatment significantly increased the expression of LGR5 (~2.38-fold change, p = 0.009) and MUC2 (~1.85-fold change, p = 0.08). Notably, in the presence of oxidative stress, Ech A attenuated oxidative stress up to 1.8-fold (p = 0.04), with a restored gene expression of LGR5 (~4.11-fold change, p = 0.0004), as well as an increased expression of Ly6a (~3.51-fold change, p = 0.005) and CLU (~2.5-fold change, p = 0.01), markers of revival stem cells. In conclusion, Ech A is harmless to intestinal tissues; rather, it promotes the maintenance and regeneration of the intestinal epithelium, suggesting possible beneficial effects on the intestine when used as an oral medication.

Marine natural products

“…612 The biological activities of specifically quinonoid sea urchin pigments, including echinochrome A, have also been reviewed, 613 with a number of new studies reporting a variety of additional biological activities for echinochrome A including regulation of inflammation related to myocardial dysfunction, 614 reduced blood pressure in a rat model of preeclampsia, 615 as a treatment for menopausal dry mouth, 616 suppression of melanin synthesis, 617 and maintenance and regeneration of intestinal epithelium cells. 618 The ecological roles played by anthraquinone pigments have been widened by the finding that host selection between crinoids and the symbiotic snapping shrimp Synalpheus stimpsonii is mediated by the pigments. 619 In addition to antioxidant properties, ovothiol appears to play a central role in the control of cell proliferation in the early stages of embryo development in the sea urchin Paracentrotus lividus .…”