Cech Research Group
The central challenge that impedes research on botanical dietarysupplements is how to address their complexity and variability. Practitioners of alternative medicine argue that this complexity results in beneficial synergistic interactions. However, the specific constituents responsible for synergistic activity, and the mechanisms by which these constituents interact, are rarely known. For the past decade, our research group has been engaged in research aimed at developing novel methods to investigate the phenomenon of synergistic interactions in complex mixtures from botanical medicines.
We have developed a novel approach “synergy-directed fractionation”, which employs mass spectrometry and synergy assays in concert to track bioactive constituents as they are isolated from a mixture. We used the medicinal plant goldenseal (Hydrastis canadensis) as a test case for this approach, and have identified a number of constituents that interact synergistically to enable H. canadensis extracts to fight bacteria. Our work in the area of synergy and botanical medicines has been featured in Chemical and Engineering News and a paper on our synergy-directed fractionation approach coauthored by our research group and that of Dr. Nicholas Oberlies was awarded the Jack L. Beal award for best journal of natural products paper by a young investigator in 2011.
The European Antimicrobial Surveillance Systems estimates that as many as 52 million people worldwide carry multi-drug resistant bacteria. Among the most prevalent and lethal of these is methicillin-resistant Staphylococcus auresus (MRSA), which now causes more deaths each year in the US than HIV/AIDS. There is a pressing need to devise new strategies to combat drug-resistant bacterial infections such as MRSA. One possible strategy is the use of multi-component treatments that target the pathogen via different mechanisms. Our research laboratory is engaged in ongoing efforts to identify mixtures of constituents from natural products (plants or endophytic fungi) that may be useful against drug resistant infections.Toward this goal, we have worked with Dr. Joseph O. Falkinham at the Virginia Polytechnic University and Dr. Rob Cannon at the University of North Carolina Greensboro to identify natural products compounds with antimicrobial activity. We also have an ongoing collaboration with Dr. Glenn Kaatz at Wayne State University to identify plant effluxpump inhibitors. Finally, we are particularly interested in compounds with anti-virulence activity, as these are less likely to lead to the development of resistance than are antimicrobial agents. Through acollaboration with Dr. Alexander Horswill at the University of Iowa, we are engaged in identifying compounds that act via quorum quenching to reduce the virulence of the pathogen. With this approach, the production of toxins by the pathogen is inhibited, enabling the host to clear the infection without pressuring the organism to become more virulent.
There is growing awareness that the bioactive constituent profile of medicinal plants can be profoundly influenced by endophyte infection. Endophytes are microorganisms (typically fungi or bacteria) that infect plant tissues, often engaged in symbiotic interactions with their hosts. These microbes can produce bioactive compounds themselves, or can alter the metabolite profile produced by the plant. Endophytes can be transmitted to the plant from the environment, or from parent to offspring via the seed. Either way, there is a great deal of variability in the type and extent of endophyte infection observed for a given plant species. This is particularly relevant to the natural products industry, because it can lead to variability in the bioactivity of plant medicines, even when they are prepared from the same genus and species of a given plant. Our research group is currently engaged in collaborative research projects with Dr. Stanley Faeth at the University of North Carolina Greensboro Department of Biology and Dr. Nicholas Oberlies at the University of North Carolina Greensboro Department of Chemistry that seek to elucidate the role of endophyte infection in the bioactivity of several medicinal plants.
The Centers for Disease Control reports that Echinacea is the third mostcommonly used herbal medicine in the US. This botanical is typically employed for treatment of upper respiratory infections, which afflict adults 2-4 times per year, and cost over $10 billion in annual medical costs. SeveralEchinacea preparations and constituents thereof have demonstrated the ability to suppress inflammation, and may, therefore, be indicated in treating the symptoms of upper respiratory infections. However, while Echinacea demonstrated promise for this purpose in some early trials, a number of recent clinical trials have shown certain Echinacea extracts to be ineffective for treatment of upper respiratory infections. These conflicting findings may be explained at least in part by lack of understanding of the active constituents and mechanisms of action for Echinaceapreparations. Our group focuses on filling these gaps, with particular emphasis on developing Echinacea preparations useful in treating the inflammation associated with infection. One aspect of this project involves identifying active anti-inflammatory constituents from the most commonly used Echinacea species, E. purpurea. In addition, with the help of Dr. Scott Laster at North Carolina State University, we are investigating the mechanisms of action for specific anti-inflammatory constituents against influenza-induced infection. Toward this goal, our research group is engaged in a comprehensive proteomics study investigating the influence of Echinacea extracts and isolated constituents on cultured immune cells. Finally, in collaboration with Dr. Jeanine Davis at North Carolina State University Richard Cech at Horizon Herbs, and farmers across the state of North Carolina, we are investigating the influence of growing conditions on Echinacea’s bioactive constituent profile.