Colon-Targeted Trans-Cinnamic Acid Ameliorates Rat Colitis by Activating GPR109A

Author:

Kang Changyu,Kim Jaejeong,Ju Sanghyun,Cho HeeyeongORCID,Kim Hyun Young,Yoon In-SooORCID,Yoo Jin-WookORCID,Jung Yunjin

Abstract

We designed colon-targeted trans-cinnamic acid (tCA) and synthesized its conjugates with glutamic acid (tCA-GA) and aspartic acid (tCA-AA). We evaluated the anti-colitic activity of colon-targeted tCA using a dinitrobenzenesulfonic acid-induced rat colitis model. The conjugates lowered the distribution coefficient and Caco-2 cell permeability of tCA and converted to tCA in the cecum, with higher rates and percentages with tCA-GA than with tCA-AA. Following oral gavage, tCA-GA delivered a higher amount of tCA to the cecum and exhibited better anti-colitic effects than tCA and sulfasalazine (SSZ), which is the current treatment for inflammatory bowel disease. In the cellular assay, tCA acted as a full agonist of GPR109A (EC50: 530 µM). The anti-colitic effects of tCA-GA were significantly compromised by the co-administration of the GPR109A antagonist, mepenzolate. Collectively, colon-targeted tCA potentiated the anti-colitic activity of tCA by effectively activating GPR109A in the inflamed colon, enabling tCA to elicit therapeutic superiority over SSZ.

Funder

National Research Foundation of Korea

Publisher

MDPI AG

Subject

Pharmaceutical Science

Reference33 articles.

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