title: Orally administered extract from Prunella vulgaris attenuates spontaneous colitis in mdr1a(-/-) mice.
abstract: OBJECTIVE
  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-1α, 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.
  
  
  CONCLUSIONS
  The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a(-/-) mice.
authors.affiliation: Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Kelley Mk
authors.initials: KM
authors.lastname: Haarberg
authors.affiliation: Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Meghan J
authors.initials: MJ
authors.lastname: Wymore Brand
authors.affiliation: Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Anne-Marie C
authors.initials: AM
authors.lastname: Overstreet
authors.affiliation: Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Hauck
authors.affiliation: Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Murphy
authors.affiliation: Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Hostetter
authors.affiliation: Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Ramer-Tait
authors.affiliation: Kelley MK Haarberg, Meghan J Wymore Brand, Anne-Marie C Overstreet, Michael J Wannemuehler, Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
keywords: Botanical extract; Inflammatory bowel disease; Mdr1a; Mucosal inflammation; Nutraceutical; Prunella vulgaris; Spontaneous colitis