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Undergraduate Research Project Management System

Investigating the Anti-Inflammatory Properties of Devil's Club

Status Current
Seeking Researchers Yes
Start Date 12/01/2012
End Date 07/01/2013
Funding Source Alaska Heart Institute
Funding Amount
Community Partner
Related Course
Last Updated 01/29/2013 03:51PM
Keywords devil's club

People

Faculty
  Colin McGill

Student Researchers
  Charles Benson

Abstract

Devil's club. Oplopanax horridus. has been widely used as a traditional medicine amongst the
indigenous peoples of Alaska and British Columbia. The root bark and berries have been used both internally and externally to treat a variety of ailments, including arthritis. cold and fever, infections. diabetes, respiratory and gastrointestinal disorders, and cancer, and remain in use as traditional medicines. Recent pharmacological studies have indicated that extracts of the root bark display hypoglycemic. antibacterial. anti-fungal and antiviral
properties, and have also shown a marked anti-proliferative efTect on human colorectal cancer cell lines.

Though most ofthe chemical composition ofthe essential oil ofDevil's club has been elucidated, as well as some phenolic constituents. there remains no specific evidence in the literature of the mechanism by which Devil' s club extract acts. Furthermore, there has been no scientific discussion to date of Devil' s club acting via an anti-inflammatory pathway, despite the inflammatory nature of many of the ailments it's purported to treat.
A more thorough understanding of the biological mechanisms by which Devil's Club acts and possible identification of the bioactive compounds contained in the root bark will validate medicinal applications of the ethnobotanical, as well as inform the development of pharmaceutical intervention strategies.

Our long range goal is to identify and characterize the anti-inflammatory action of Devil's club extract as well as discern relevant bioactive compounds. to provide groundwork for the development of novel pharmaceuticals to treat neuronal inflammation. The objective {~!'this proposal, the next step in pursuit of this goal. is to determine if treatment of SH-SY5Y human neuroblastomas with Devil's club extract decreases tumor necrosis factor (TNF-a)-mediated production of reactive oxygen species (ROS) and decreases activation of
neutral sphingomyelinase (nSMase). The cenlrcr! hypothesis is that Devil's club extract reduces indices of inflammation in neuroblastomas insulted by tumor necrosis factor-alpha (TNFa) compared to controls which exclude Devil's club extract treatments. The rationale for this proposal is that elucidating the anti-inflammatory mechanism by which Devil's club operates will provide the base needed for the successful development of similar neuroprotective pharmaceutical agents. We expect to test our central hypothesis and accomplish our objective by carrying-out the following specific aims:

A. Determine if Devil's Club extract reduces intracellular levels of total ROSin TNFa-insulted neuroblastoma cells. It is well documented that treatment of SH-SY5Y human neuroblastomas with TNFa leads to elevated NADPll oxidase-mediated ROS production. The working hypothesis for this aim is that pretreatment of the neuroblastomas with Devil's club extract prior to TNFa insult will result in decreased ROS production compared to controls treatments excluding Devil's club extract.

B. Determine if Devil's club extract inhibits nSMase activation in TNFa- insulted neuroblastoma cells. It is well documented that treatment or SH-SY5Y human neuroblastomas with TNFa leads to increased activation of the ceramidase enzyme nSMase. The working hypothesis for this aim is that intracellular nSMasc activation will increase following TNFa exposure and that pretreatment ~ith Dcvil's club extract will result in decreased nSMase activation.

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