Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a^-/- mice

Authors

Kelley M.K. Haarberg, Iowa State University
Meghan J. Wymore Brand, Iowa State University
Anne-Marie C. Overstreet, Iowa State University
Catherine C. Hauck, Iowa State University
Patricia A. Murphy, Iowa State University
Jesse M. Hostetter, Iowa State University
Amanda Ramer-Tait, University of Nebraska-LincolnFollow
Michael J. Wannemuehler, Iowa State University

Date of this Version

11-6-2015

Citation

World J Gastrointest Pharmacol Ther 2015 November 6; 6(4): 223-237 ISSN 2150-5349 (online).

Comments

Copyright © 2015 Baishideng Publishing Group Inc. All rights reserved. Used by permission.

Abstract

AIM: To investigate the ability of a Prunella vulgaris (P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a^-/- mice.

METHODS: Vehicle (5% ethanol) or P. vulgaris ethanolic extract (2.4 mg/d) were administered daily by oral gavage to mdr1a^-/- or wild type FVB^WT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencing weight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity.

RESULTS: Administration of P. vulgaris extracts to mdr1a^-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced (P < 0.05) serum levels of IL-10 (4.6 ± 2 vs 19.4 ± 4), CXCL9 (1319.0 ± 277 vs 3901.0 ± 858), and TNFα (9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a^-/- mice compared to vehicle-treated mdr1a^-/- mice. Histologically, several microscopic parameters were reduced (P < 0.05) in P. vulgaris -treated mdr1a^-/- mice, as was myeloperoxidase activity in the colon (2.49 ± 0.16 vs 3.36 ± 0.06, P < 0.05). The numbers of CD4⁺ T cells (2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells (2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris - treated mdr1a^-/- were significantly reduced (P < 0.05) from vehicle-treated mdr1a^-/- mice. Vehicle-treated mdr1a^-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris -treated mdr1a^-/- mice.

CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a^-/- mice.