Molecular nutrition & food researchFeb 10, 2025

Ashitaba Compound 4-Hydroxyderricin Boosts Gut Hormone Release and Reduces Blood Sugar After Meals in Mice

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

4-hydroxyderricin (4-HD) stimulates GLP-1 secretion and improves glucose tolerance.

4-HD induces GLP-1 secretion in intestinal cells by causing membrane depolarization and increasing calcium levels through L-type calcium channels.
The effects of 4-HD on calcium levels and GLP-1 secretion are blocked by the calcium channel blockers verapamil and nifedipine, as well as in a calcium-free environment.
4-HD activates proteins CaMKII and ERK1/2, which are involved in cellular signaling.
In male ICR mice, oral administration of 4-HD reduces postprandial hyperglycemia and increases plasma levels of GLP-1 and insulin.
4-HD promotes GLUT4 translocation and activates the LKB-1 and Akt pathways in skeletal muscle.
Inhibition of GLP-1 receptors or AMPK completely negates the antihyperglycemic effects of 4-HD.

Simplified

Certain polyphenols improve glucose tolerance by stimulating glucagon-like peptide-1 (GLP-1) secretion from intestinal L-cells. Ashitaba chalcones, 4-hydroxyderricin (4-HD), and xanthoangelol (XAG) have antihyperglycemic effects, but their molecular mechanism, including whether they promote GLP-1 secretion is unknown. This study investigates the 4-HD-induced GLP-1 secretory mechanisms and its anti-hyperglycemic effects. The secretory mechanisms were examined in STC-1 cells and antihyperglycemic effects in male ICR mice. In STC-1 cells, 4-HD, but not XAG, stimulated GLP-1 secretion through membrane depolarization and intracellular Caincrease [Ca], via the L-type Cachannel (VGCC). Verapamil and nifedipine, blockers of VGCC, and treatment in Ca-free buffer abolished 4-HD effects on [Ca]and GLP-1 secretion. Moreover, 4-HD activated CaMKII and ERK1/2. Consistently, oral 4-HD suppressed postprandial hyperglycemia in mice and increased plasma GLP-1 and insulin levels, GLUT4 translocation, and activation of LKB-1 and Akt pathways in skeletal muscle. Furthermore, exendin 9-39, a GLP-1R antagonist, and compound C, an AMPK inhibitor, completely canceled the 4-HD-caused anti-hyperglycemic activities. 4-HD stimulated GLP-1 secretion through membrane depolarization coupled with [Ca]increase via VGCC in L-cells and activated AMPK- and insulin-induced GLUT4 translocation in skeletal muscle. Thus, 4-HD possesses dual mechanisms for the prevention of hyperglycemia. 2+ 2+ 2+ 2+ 2+ 2+ i i i

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Ashitaba Compound 4-Hydroxyderricin Boosts Gut Hormone Release and Reduces Blood Sugar After Meals in Mice

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