Bushi-richu-to Raises Calcitonin Gene-related Peptide, Substance P, Somatostatin, and Vasoactive Intestinal Polypeptides Levels in Human Plasma

Abstract

The traditional Japanese Kampo medicine Bushirichu-to (Bushi-ninjin-to) has been empirically used for the treatment of chronic gastroenteritis, gastric atony, and chronic constipation accompanied by a feeling of coldness in the body. One of the mechanisms of the empirical effects is assumed to be due to local changes in gut-regulated peptide levels. We studied the effect of Bushi-richu-to on calcitonin gene-related peptide (CGRP)-, substance P-, vasoactive intestinal polypeptides (VIP)-, somatostatin-, and motilin-like immunoreactive substances (IS) in plasma taken from healthy subjects. Bushi-richuto (4.5 g) or placebo was orally administered to five healthy males. Blood samples were taken before, and at 20, 40, 60, 90, 120, 180, and 240 min after administration, extracted, and then submitted to a highly sensitive enzyme immunoassay system for CGRP-, substance P-, VIP-, somatostatin-, and motilin-IS. A single oral administration of Bushi-richu-to caused significant increases in plasma CGRP-, substance P-, VIP-, and somatostatin-IS levels compared with placebo. It is concluded that Bushi-richu-to might improve a peripheral and uncomfortable feeling of cold and gastrointestinal dysmotility via gut-regulated peptide release.