Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

Abstract

Sensory afferent neurons in the gastrointestinal mucosa regulate neuropeptides [calcitonin gene-related peptide (CGRP), substance P, etc.], which play various physiologic roles and are gastroprotective. To determine whether the pharmacologic effects of Dai-kenchu-to (DKCT) on the gastrointestine are due to changes in gastrointestinal mucosa regulatory peptide levels, we examined the effects of the DKCT on the levels of CGRP-like immunoreactive substances (IS) and substance P-IS in plasma taken from five healthy subjects. A single oral administration of DKCT 7.5 g caused significant increases in plasma CGRP-IS at 40 min, and in substance P-IS levels at 20 and 60 min, compared with a placebo group. The present study may indicate that the pharmacologic action of DKCT is closely related to changes in CGRP-and substance P-IS levels.

Comparison of the Effects of Pantethine and Fursultiamine on Plasma Gastrointestinal Peptide Levels in Healthy Volunteers

“…[6][7][8] The traditional herbal medicines Dai-kenchu-to and Ninjin-to, which are used to treat postoperative ileus, have been reported to raise plasma levels of CGRP and SP in humans. 13,14) In this study, we examined the effects of pantethine and fursultiamine on CGRP, VIP, motilin and SP, which are peptides that regulate gastrointestinal motility.…”

“…Synthetic human CGRP and its fragment , VIP, motilin and SP were purchased from Peptide Institute, Inc. (Osaka, Japan). VIP fragment (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) was supplied by Professor H. Yajima (Kyoto University, Kyoto, Japan). Antiserum to CGRP (14160) was purchased from Peptide Institute, Inc. (Osaka, Japan), VIP (T-4116) from Peninsula Laboratories (California, U.S.A.), and motilin (Y121) and SP (Y150) from Yanaihara Institute (Shizuoka, Japan).…”

“…An anti-rabbit IgG-(55641, ICN Pharmaceuticals, Inc., Ohio, U.S.A.) coated immunoplate (Nunc-Immuno Module Maxisorp F8, InterMed, Denmark) was used to separate bound and free antigens. Human CGRP fragment (8-37), VIP fragment (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28), motilin and SP were conjugated with b-galactosidase by N-(emaleimido-caproyloxy)-succimide according to the methods of Kitagawa et al 19) The enzyme immunoassays for CGRP-, VIP-, motilin-and SP-IS were specific and highly sensitive, with detection limits of 4.0, 8.0, 0.25 and 0.25 pg/ml, respectively.…”

“…All subjects had no history of gastrointestinal disease and their baseline fasting plasma levels of CGRP-, VIP-, motilin-and SP-IS were within the normal ranges for healthy subjects reported previously. [6][7][8]13,14) The study was approved by the Ethics Committee of Oita Medical University. Each subject received information about the scientific purpose of the study, and gave informed consent.…”

“…Dai-kenchu-to and Ninjin-to, the traditional herbal medicines used to treat postoperative ileus, have been shown to raise CGRP and SP levels in human plasma. 13,14) The effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in humans have not been demonstrated. Therefore, we examined the effects of these two compounds on plasma levels of CGRP-, VIP-, motilin-and SP-like immunoreactive substances (IS) in healthy subjects.…”