5-HT(3) and 5-HT(4) receptors contribute to the anti-motility effects of Garcinia buchananii bark extract in the guinea-pig distal colon

• Published in: Neurogastroenterology and motility 2012-01, Vol.24 (1), p.e27-e40
• Main Authors: Boakye, P A, Stenkamp-Strahm, C, Bhattarai, Y, Heckman, M D, Brierley, S M, Pasilis, S P, Balemba, O B
• Format: Article
• Language: English
• Subjects: Animals; Child; Colon - drug effects; Colon - physiology; Garcinia - anatomy & histology; Garcinia - chemistry; Gastrointestinal Motility - drug effects; Guinea Pigs; Humans; Plant Bark - chemistry; Plant Extracts - pharmacology; Receptors, Serotonin, 5-HT3 - metabolism; Receptors, Serotonin, 5-HT4 - metabolism; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology
• ISSN: 1365-2982
• DOI: 10.1111/j.1365-2982.2011.01807.x

Garcinia buchananii bark extract is an anti-motility diarrhea remedy. We investigated whether G. buchananii bark extract has components that reduce gastrointestinal peristaltic activity via 5-HT(3) and 5-HT(4) receptors. Aqueous G. buchananii extract was separated into fractions using preparative thin layer chromatography (PTLC), and major chemical components were identified using standard tests. The anti-motility effects of the extract and its fractions (PTLC1-5) were studied through pellet propulsion assays using isolated guinea-pig distal colons. Anti-motility (PTLC1 & PTLC5) and pro-motility (PTLC2) fractions were isolated from the extract. Flavonoids, steroids, alkaloids, tannins, and phenols were identified in the extract and PTLC1&5. The potency of the extract applied via the mucosal surface was reduced by 5-HT, 5-HT(3) receptor agonist RS-56812, 5-HT(4) receptor agonists cisapride and CJ-033466, 5-HT(3) receptor antagonist granisetron, and 5-HT(4) receptor antagonist GR-113808. The anti-motility effects of the aqueous extract and PTLC1&5 when applied serosally were reversed by RS-56812, cisapride, and CJ-033466. The 5-HT(3) receptor antagonists, granisetron and ondansetron, reduced the effects of the extract to an extent and completely reversed the anti-motility effects of PTLC1&5. GR-113808 inhibited the actions of the extract during the initial 10 min, but enhanced the extracts' anti-motility effects after 15 min. GR-113808 augmented the anti-motility activities of PTLC1 and PTLC5 by 30%. These results indicate that the anti-motility effects of G. buchananii aqueous extract are potentially mediated by compounds that affect 5-HT(3) and 5-HT(4) receptors. Identification and characterization of the bioactive compounds within G. buchananii could lead to the discovery of new non-opiate anti-diarrhea formulations.