Effect of a Single Treatment with Keishininjinto on Plasma Levels of Gut-regulatory Peptides in Healthy Subjects

Abstract

A traditional Japanese Kampo medicine Keishininjinto has been empirically used for the treatment of headache, chronic gastroenteritis, gastric atony, and waterly diarrhea often accompanying abdominal pain, cold, fever, and headache. One of the mechanisms of the empirical effects is assumed to be due to local changes in gut-regulated peptide levels. We studied the effects of Keishininjinto on calcitonin gene-related peptide (CGRP)-, substance P-, vasoactive intestinal polypeptides (VIP)-, motilin-, and somatostatin-like immunoreactive substances (IS) in plasma taken from healthy subjects. Keishininjinto (6.0 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, followed by the extracting procedure, and submitted to a highly sensitive enzyme immunoassay system for CGRP-, substance P-, VIP-, motilin-, and somatostatin-IS. A single oral administration of Keishininjinto caused significant increases in plasma CGRP-, and substance P-IS levels compared with placebo. On the other hand, a single oral administration of Keishininjinto transiently caused decreases in plasma VIP-IS levels compared with placebo. However, Keishininjinto had no effects on plasma motilin-, and somatostatin-IS levels. In this study, we hypothesized that Keishininjinto might stimulate capsaicinsensitive afferent nerves and improve gastrointestinal mucosal blood flow, and that might affect intestinal secretion and motility in neuronal reflexes.

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

“…7) It is know that this herb or some Kampo medicines which include this herb increased plasma CGRP-IS levels in human subjects. 11,24,25) Accordingly, Bushi-richu-to may also directly stimulate CGRP-containing nerves or indirectly secrete CGRP accompanied by the stimulation of other secretory cells and mechanisms. The mechanisms of Bushi-richu-to, based on the increment of CGRP-IS levels in human plasma, might include not only the improvement of peristaltic contractions but also increments in intestinal blood flow, both of which are mediated by CGRP.…”

“…Dai-kenchuto, Ninjin-to and Keishi-ninjin-to affect gastrointestinal motility and based on empirical evidence their effects are assumed to be an alteration of gut-regulated peptides levels in healthy human plasma. [9][10][11] Among these drugs, it is reported that Ninjin-to potentially enhances gastrointestinal motility in a manner similar to that of gastrointestinal prokinetic drugs like cisapride and meto-clopramide. 12) Ninjin-to and Bushi-richu-to contain the same herbs (Ginseng radix, Glycyrrhizae radix, Atractylodis rhizome, and Zingiberis siccatum rhizome).…”