Study on the Therapeutic Effects and Mechanisms of Gintonin in Irritable Bowel Syndrome and Its Relationship with TRPV1, TRPV4, and NaV1.5

Author:

Choi Na-Ri12ORCID,Ko Seok-Jae34ORCID,Nam Joo-Hyun56ORCID,Choi Woo-Gyun1ORCID,Lee Jong-Hwan7,Nah Seung-Yeol8ORCID,Park Jae-Woo34,Kim Byung-Joo1

Affiliation:

1. Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea

2. Department of Korean Medical Science, Pusan National University School of Korean Medicine, Yangsan 50612, Republic of Korea

3. Department of Clinical Korean Medicine, Graduate School of Kyung Hee University, Seoul 02447, Republic of Korea

4. Department of Gastroenterology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

5. Department of Physiology, Dongguk University College of Medicine, Kyungju 38066, Republic of Korea

6. Channelopathy Research Center (CRC), Dongguk University College of Medicine, Goyang 10326, Republic of Korea

7. Department of Biomedical Engineering, Dong-Eui University College of Engineering, Busan 47340, Republic of Korea

8. Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea

Abstract

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action of gintonin in IBS, we developed a zymosan-induced IBS murine model. In addition, electrophysiological experiments were conducted to confirm the relevance of various ion channels. In mice, gintonin restored colon length and weight to normal and decreased stool scores, whilst food intake remained constant. Colon mucosal thickness and inflammation-related tumor necrosis factor-α levels were decreased by gintonin, along with a reduction in pain-related behaviors. In addition, the fecal microbiota from gintonin-treated mice had relatively more Lactobacillaceae and Lachnospiraceae and less Bacteroidaceae than microbiota from the control mice. Moreover, gintonin inhibited transient receptor potential vanilloid (TRPV) 1 and TRPV4 associated with visceral hypersensitivity and voltage-gated Na+ 1.5 channels associated with GI function. These results suggest that gintonin may be one of the effective components in the treatment of IBS.

Funder

Basic Science Research Program through the National Research Foundation of Korea

Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Korean government

Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea

Publisher

MDPI AG

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