Inflammatory Bowl Disease (IBD): Colitis

1. Lavender Protects Against Infectious ColitisJessica BakerSupervisor: Dr. Deanna GibsonUBC MURC 2011

2. Inflammatory Bowl Disease (IBD): Colitis • IBD: Ulcerative Colitis and Crohn’s Disease • It is a chronic, relapsing, immunologically-mediated disorder in the gastrointestinal tract • Unknown cause, although onset and activation is thought to develop in predisposed individuals • Currently there are limited therapeutic options

3. Bacteria-Induced Colitis Model • Use a bacterium called Citrobacter rodentium: a mouse-specific intestinal pathogen • Some important inflammatory factors: • TNF-α, IFN-γ, iNOS, IL-22, MIP-2α and IL-10 • Results in intestinal damage similar to human colitis

4. Lavandula x intermedia: Okanagan Lavender • Developed in Dr. Soheil Mahmoud’s Lab at UBC Okanagan • Objective: to improve oil composition and yield Desautels, A, et al. “Suppression of Linalool Acetate production in Lavandula x intermedia.”Natural Products Communications 4.11 (2009): 1533-1536. Santos, F.A., et al. “1,8-cineole (eucalyptol), a monoterpene oxide attenuates the colonic damage in rats on acute TNBS-colitis.” Food and Chemical Toxicology 42 (2004): 579-584. Tung, Yu-Tang, et al. “Anti-inflammation activities of essential oil and its constituents from indigenous cinnamon (Cinnamomumosmophloeum) twigs.” Bioresource Technology 99 (2008): 3908-3913.

5. Hypothesis • We hypothesize that Okanagan Lavender oil will decrease the severity of infectious colitis due to its ability to increase pathogen clearance as well as its ability to decrease inflammation and associated inflammatory mediators

6. B6 (C57BL/6) Mice OR C3H (C3H/HeOuJ) Mice Procedure: Group 1: Mineral oil OR Group 2: Lavender oil Orally gavaged throughout 10-day infection Orally gavaged with C. rodentium for 10 days Monitored morbidity and mortality

7. Lower Gastrointestinal Tract Cecum RNAlater: extract the RNA for q-PCR H&E stain: Scoring Distal Colon Spleen AND Bacterial counts to assess systemic infection Mesenteric Lymph Nodes

8. B6 Mice C3H Mice • Lavender-treated mice susceptible to lethal infectious colitis (C3H mice) showed a drastic decrease in mortality • Lavender-treated mice that survive colitis (B6 mice) showed significantly less morbidity (P< 0.05; Mann-Whitney T-test)

9. micrographs of the cecum Uninfected Infected + Mineral Oil Infected + Lavender Oil • Lavender Oil significantly reduces • Edema • Infiltration • Epithelial hyperplasia • Goblet cell depletion • Epithelial damage • (P< 0.01, Mann-Whitney T-test)

10. In Vitro and In Vivo Evidence That Lavender Oil Can Directly Kill This Pathogen In Vivo In Vitro MLN Mineral Oil Lavender Oil Colony Forming Units Spleen Lavender Mineral Oil Oil

11. q-PCR Results The mice orally gavaged with lavender oil showed a significant modulation in the immune response (P< 0.05, Mann-Whitney T-test)

12. Immunofluorescence Results Infected + Infected + Lavender-treated mice showed a drastic decrease in immune cell infiltration

13. Conclusion • The significant decrease in morbidity, cecal tissue damage, pro-inflammatory cytokine production and immune cell infiltration provide strong support for our hypothesis that Okanagan Lavender Oil protects against infectious colitis • Two mechanisms • Antimicrobial • Immune Modulation

14. Future • Results so far warrant further analysis • Isolate and test Lavender components • Need to do more animal studies with higher N number and varied dose amounts • Need to examine overall health in other areas of the body • Potential outcomes: • An anti-inflammatory drug for chronic intestinal diseases such as colitis • An antimicrobial drug for intestinal infectious diseases

15. Acknowledgments • Dr. Deanna Gibson (Supervisor) • Dr. Soheil Mahmoud and Lab • Dr. SanjoyGhosh • Samantha Makarenko • Kirsty Brown • Dr. Mark Rheault • Brie Matier • Irving K. Barber Endowment fund • Everyone with MURC 2011