L AVENDER P ROTECTS A GAINST I NFECTIOUS C OLITIS J ESSICA B AKER S UPERVISOR : D R. D EANNA G IBSON UBC MURC 2011.

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L AVENDER P ROTECTS A GAINST I NFECTIOUS C OLITIS J ESSICA B AKER S UPERVISOR : D R. D EANNA G IBSON UBC MURC 2011

I NFLAMMATORY B OWL D ISEASE (IBD): C OLITIS 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

B ACTERIA -I NDUCED C OLITIS M ODEL 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

L AVANDULA X INTERMEDIA : O KANAGAN L AVENDER Developed in Dr. Soheil Mahmoud’s Lab at UBC Okanagan Objective: to improve oil composition and yield TerpeneWild Type OilOkanagan Lavender Oil Cineole (%)13.73 ± ± 1.78 Camphor (%)11.16 ± ± 0.26 Linalool (%)35.92 ± ± 4.16 Linalool acetate (%)25.34 ± ± 0.36 Borneol (%)3.55 ± ± 3.63 Desautels, A, et al. “Suppression of Linalool Acetate production in Lavandula x intermedia.”Natural Products Communications 4.11 (2009): 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): Tung, Yu-Tang, et al. “Anti-inflammation activities of essential oil and its constituents from indigenous cinnamon (Cinnamomum osmophloeum) twigs.” Bioresource Technology 99 (2008):

H YPOTHESIS 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

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

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

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) B6 Mice C3H Mice

MICROGRAPHS OF THE CECUM Lavender Oil significantly reduces Edema Infiltration Epithelial hyperplasia Goblet cell depletion Epithelial damage (  P< 0.01, Mann-Whitney T-test) Uninfected Infected + Mineral Oil Infected + Lavender Oil

I N V ITRO AND I N V IVO E VIDENCE T HAT L AVENDER O IL C AN D IRECTLY K ILL T HIS P ATHOGEN Mineral Oil Lavender Oil Lavender Mineral Oil Oil Colony Forming Units MLN Spleen In VivoIn Vitro

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

I MMUNOFLUORESCENCE R ESULTS Infected + Lavender-treated mice showed a drastic decrease in immune cell infiltration

C ONCLUSION 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 TerpeneOkanagan Lavender Oil Cineole (%)27.09 ± 1.78 Camphor (%)3.03 ± 0.26 Linalool (%)36.28 ± 4.16 Linalool acetate (%)1.86 ± 0.36 Borneol (%) ± 3.63

F UTURE 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

A CKNOWLEDGMENTS Dr. Deanna Gibson (Supervisor) Dr. Soheil Mahmoud and Lab Dr. Sanjoy Ghosh Samantha Makarenko Kirsty Brown Dr. Mark Rheault Brie Matier Irving K. Barber Endowment fund Everyone with MURC 2011