Tags

Type your tag names separated by a space and hit enter

Salvinorin A has antiinflammatory and antinociceptive effects in experimental models of colitis in mice mediated by KOR and CB1 receptors.
Inflamm Bowel Dis. 2012 Jun; 18(6):1137-45.IB

Abstract

BACKGROUND

Salvinorin A (SA) has a potent inhibitory action on mouse gastrointestinal (GI) motility and ion transport, mediated primarily by kappa-opioid receptors (KOR). The aim of the present study was to characterize possible antiinflammatory and antinociceptive effects of SA in the GI tract of mice.

METHODS

Colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western blot analysis of colon samples was performed. The antinociceptive effect of SA was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO).

RESULTS

The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg, twice daily) administration of SA significantly attenuated TNBS and DSS colitis in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10 mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2 levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists. The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to controls.

CONCLUSIONS

Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases.

Authors+Show Affiliations

Snyder Institute of Infection, Immunity and Inflammation (III), University of Calgary, AB, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21953882

Citation

Fichna, Jakub, et al. "Salvinorin a Has Antiinflammatory and Antinociceptive Effects in Experimental Models of Colitis in Mice Mediated By KOR and CB1 Receptors." Inflammatory Bowel Diseases, vol. 18, no. 6, 2012, pp. 1137-45.
Fichna J, Dicay M, Lewellyn K, et al. Salvinorin A has antiinflammatory and antinociceptive effects in experimental models of colitis in mice mediated by KOR and CB1 receptors. Inflamm Bowel Dis. 2012;18(6):1137-45.
Fichna, J., Dicay, M., Lewellyn, K., Janecka, A., Zjawiony, J. K., MacNaughton, W. K., & Storr, M. A. (2012). Salvinorin A has antiinflammatory and antinociceptive effects in experimental models of colitis in mice mediated by KOR and CB1 receptors. Inflammatory Bowel Diseases, 18(6), 1137-45. https://doi.org/10.1002/ibd.21873
Fichna J, et al. Salvinorin a Has Antiinflammatory and Antinociceptive Effects in Experimental Models of Colitis in Mice Mediated By KOR and CB1 Receptors. Inflamm Bowel Dis. 2012;18(6):1137-45. PubMed PMID: 21953882.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Salvinorin A has antiinflammatory and antinociceptive effects in experimental models of colitis in mice mediated by KOR and CB1 receptors. AU - Fichna,Jakub, AU - Dicay,Michael, AU - Lewellyn,Kevin, AU - Janecka,Anna, AU - Zjawiony,Jordan K, AU - MacNaughton,Wallace K, AU - Storr,Martin A, Y1 - 2011/09/26/ PY - 2011/06/21/received PY - 2011/08/04/accepted PY - 2011/9/29/entrez PY - 2011/9/29/pubmed PY - 2012/10/26/medline SP - 1137 EP - 45 JF - Inflammatory bowel diseases JO - Inflamm Bowel Dis VL - 18 IS - 6 N2 - BACKGROUND: Salvinorin A (SA) has a potent inhibitory action on mouse gastrointestinal (GI) motility and ion transport, mediated primarily by kappa-opioid receptors (KOR). The aim of the present study was to characterize possible antiinflammatory and antinociceptive effects of SA in the GI tract of mice. METHODS: Colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and oral (p.o.) administration of SA using the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, KOR, cannabinoid (CB)1, and CB2 western blot analysis of colon samples was performed. The antinociceptive effect of SA was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO). RESULTS: The i.p. (3 mg/kg, twice daily) and p.o. (10 mg/kg, twice daily) administration of SA significantly attenuated TNBS and DSS colitis in mice. The effect of SA was blocked by KOR antagonist nor-binaltorphimine (10 mg/kg, i.p.). Western blot analysis showed no influence of SA on KOR, CB1, or CB2 levels. SA (3 mg/kg, i.p. and 10 mg/kg, i.c.) significantly decreased the number of pain responses after i.c. instillation of MO in the vehicle- and TNBS-treated mice. The antinociceptive action of SA was blocked by KOR and CB1 antagonists. The analgesic effect of i.c. SA was more potent in TNBS-treated mice compared to controls. CONCLUSIONS: Our results suggest that the drugs based on the structure of SA have the potential to become valuable antiinflammatory or analgesic therapeutics for the treatment of GI diseases. SN - 1536-4844 UR - https://www.unboundmedicine.com/medline/citation/21953882/Salvinorin_A_has_antiinflammatory_and_antinociceptive_effects_in_experimental_models_of_colitis_in_mice_mediated_by_KOR_and_CB1_receptors_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=21953882.ui DB - PRIME DP - Unbound Medicine ER -