A Walk in the Botanical Research Centers "Garden"
Russian tarragon (Artemisia dracunculus)
© 2004 Antonie van den Bos, aycronto.com
This article focuses on three of NIH's Botanical Research Centers (BRCs). Others will be profiled in future issues. For recent papers based on BRC presentations at the 2007 Experimental Biology Annual Meeting, see References.—Editor
In the large, diverse "garden" of research that NCCAM supports, the NIH Botanical Research Centers (BRC) Program is one colorful, meticulously cultivated corner. Walk down its paths, and you'll see, for example, grass-like blades of Russian tarragon, with its mild scent and taste of anise; tiny blue flowers of echium and borage, cousins in the forget-me-not family (Boraginaceae); and tall spikes of echinacea, named from a Greek term meaning sea urchin or hedgehog for the flower's spiny center.
Each plant is part of a research program that ascends a trellis of plant and medical knowledge. This program extends from the genetic materials in seeds up to finished products, and from basic biology up to health-related effects in people. Also of interest are how and why the effects of these botanicals occur and factors that may affect their activity, such as where the plant grows; how it is harvested; whether it is taken as an extract, tablet, or tea, or in another form; dosages; and how the constituents (ingredients) interact with each other.
Roots of the BRC Program
The BRC Program is sponsored by NCCAM and the NIH Office of Dietary Supplements (ODS). The program began in 1999, when Congress appropriated funds for ODS to develop a botanical research center initiative. Currently, there are six BRCs, with many features in common:
- Research activities range from identifying plants to conducting early phase clinical studies; preclinical research is the primary focus.
- The research is collaborative and integrated, and involves a number of disciplines. Experts on one project might include plant biologists, pharmacognosists (experts in the study of drugs from natural sources), clinicians, toxicologists, statisticians, and experts in high-technology research techniques.
- Each center is a partnership among institutions.
- Each uses advanced technologies and innovative research approaches.
- Each team seeks to identify and describe chemically the botanicals under study and their constituents of potential health interest.
- Many of the plant products have a history of use as traditional herbal medicines (also called phytomedicines); most are also available as dietary supplements.
- Each center is organized around a theme with substantial potential for benefiting people's health.
Testing Popular Therapies, Addressing Disease Burdens
Many Americans are using botanicals and other supplements as CAM. For example, the 2002 National Health Interview Survey found that, in the previous year, 19 percent of the people surveyed (which translates to over 38 million adults) had used natural products, a diverse category that includes herbs and other botanical products.
"Millions of Americans are using natural products, including those from plants, as CAM," says Josephine P. Briggs, M.D., Director of NCCAM. "Careful scientific investigation of these therapies is necessary. While in many cases there is a long tradition of use, we need to verify scientifically the conditions under which a botanical therapy is effective, as well as any risks to health. The BRCs study a variety of widely consumed botanicals to verify their identity, biological and chemical activity, and safety, as well as their potential health effects in diseases such as asthma, cardiovascular diseases, cataracts, and cancer. These studies are helping to move the entire field of scientific research on phytomedicines forward."
"The Dietary Supplement Health and Education Act of 1994 assured consumers access to a variety of dietary supplements, including products with botanical ingredients," says Paul M. Coates, Ph.D., Director of ODS. "The NIH BRC Program has renewed interest in natural products research with a specific focus on botanicals. Appreciation of the complexity of botanicals demands a new research model that considers the many components of botanicals and their potential effects on multiple biological targets."
Echinacea and St. John's Wort To Treat Infection
Echinacea tennesseensis flourishes in a field cage at the Iowa center. The cage, about 5' by 5' by 21', helps isolate this species of echinacea from others so that the researchers can regenerate seeds that are true to type. It also keeps out leafhoppers, pests that carry Aster yellows, a serious disease that affects echinacea. A hive of bees in each cage performs pollination.
Photo by A. Paul Ovrom
Diane Birt, Ph.D., and her colleagues at the Iowa Center for Research on Dietary Botanical Supplements study two widely used botanicals, echinacea and St. John's wort (Hypericum perforatum), and their effects in the laboratory on the viral, inflammatory, and pain aspects of infection. The center is a collaboration between Iowa State University (ISU), the University of Iowa, and the U.S. Department of Agriculture's North Central Regional Plant Introduction Station (NCRPIS). Dr. Birt is professor and chair of the food science and nutrition department at ISU in Ames, Iowa, and director of that university's Nutrition and Wellness Research Center.
Honeybees buzz in individual field cages of very pure plants at the Agriculture Department's station, which obtains, conserves, and conducts research on plant germplasm (genetic material). NCRPIS owns and maintains specimens of more than 48,000 varieties of plants—more than 150 of echinacea alone. Thus, center investigators have access to a resource with a wide variety of plants that are well documented and defined, and are grown, harvested, and stored under controlled conditions.
This team is also studying factors that influence the constituents that are bioactive (i.e., cause an effect in living organisms) such as genetic, growth, harvest, and environmental factors, and which human populations could benefit most or be at the most risk from using these botanicals.
Among the findings that Dr. Birt and her colleagues have presented so far:
Dr. Mark Widrlechner and Dr. Diane Birt of the Iowa center.
ISU photo by Bob Elbert
- Certain compounds in echinacea appear to have "promising" antiviral activities against HIV.
- Some anti-inflammatory effects from echinacea have been observed; how much varied by species. Out of nine species, Echinacea (E.) sanguinea had the most effects, followed by E. angustifolia, E. pallida, and E. simulate. These effects seem more likely to be, the researchers say, from interactions of complex chemicals than from single compounds.
- An echinacea preparation appeared to be "a potent agonist" of a specific pain receptor in mammals, TRPV1—it appeared to bind to this pain receptor on cells, possibly mimicking one aspect of how the body relieves pain.
Their future work will include studies of the herb prunella (self-heal) for antiviral and anti-inflammatory properties; work to find out more about how the herbs' bioactive ingredients have effects in the body; and clinical trials.
Oils From Botanicals To Treat Inflammatory Diseases
Borage
© Steven Foster
Many people have heard that "fish oil is good for you"-a message that typically refers to substances called essential fatty acids (EFAs) plentiful in the oils of certain fish. However, fish oil may not be the only approach to obtaining some of those reported benefits in supplement form.
The Wake Forest and Brigham and Women's Center for Botanical Lipids is studying dietary supplements based on EFAs from the seed oils of flaxseed, echium, and borage plants. The center is a collaboration between Wake Forest University, Winston-Salem, North Carolina, and Brigham and Women's Hospital, Boston. Floyd Chilton, Ph.D., a professor in Wake Forest's department of physiology and pharmacology, is the principal investigator. The disease focus at the center is chronic inflammatory diseases, especially asthma and atherosclerosis, or hardening and narrowing of the arteries. One in three Americans will have an inflammatory disease by the year 2028, the investigators report—diseases such as heart disease, asthma, arthritis, diabetes, lupus, or Crohn's disease.
Floyd Chilton, Ph.D.
© Wake Forest University
Among their findings so far:
- Mice models of atherosclerosis were fed a controlled diet with palm oil, echium oil, and/or fish oil added as their fat source. Those that received either echium oil or fish oil showed a marked drop in total plasma cholesterol and in plasma triacylglycerol (a type of triglyceride). In contrast, those receiving a palm oil diet had an increase in these biomarkers. A similar human study from this center has demonstrated that echium oil reduces triglycerides in patients with elevated triglyceride levels.
- Leukotrienes are chemicals in the body known to play a role in the inflammation associated with asthma. Researchers found that giving healthy volunteers borage supplements (rich in an EFA called GLA) markedly inhibited their leukotriene production. However, this supplement also increased production of another substance that has the opposite effect, arichidonic acid (AA). By adding fish oil supplements (rich in another EFA called EPA) to this regimen, they maintained a drop in leukotriene production without increasing circulating AA. They also demonstrated a marked reduction in the expression of several critical inflammatory genes.
Botanicals for Metabolic Syndrome
Many health agencies and experts have described an epidemic of obesity in the United States. One aspect of obesity is a related and also increasingly prevalent disorder called metabolic syndrome. In this syndrome, a person has a cluster of conditions that have been shown to increase risk for developing cardiovascular diseases (such as heart disease and stroke), including high blood pressure, high levels of triglycerides, low levels of good cholesterol, obesity, intolerance to glucose (sugar), as well as a condition called insulin resistance.
The Center for the Study of Botanicals and Metabolic Syndrome is investigating new botanical approaches in this area. The center is a collaboration between the Pennington Biomedical Research Center and the Agriculture Center, Louisiana State University (LSU), Baton Rouge, and the Biotechnology Center of Agriculture and the Environment, Rutgers University, New Brunswick, New Jersey. William Cefalu, M.D., professor and chief of Pennington's Division of Nutrition and Chronic Disease, is the principal investigator.
Dr. Cefalu and his colleagues are conducting basic and clinical studies to determine how certain botanicals might treat, or delay the progression of, insulin resistance, a key feature of metabolic syndrome: Russian tarragon (Artemisia dracunculus), shilianhua (Sinocrassula indica, an herb native to China), and a class of chemicals called anthocyanins from the skins of grapes; they also give berry fruits their colors. The group also hopes to gain further insight at the cellular level about how people develop metabolic syndrome. The center uses hydroponic greenhouse cultivation to enhance the production and consistency of the study botanicals and their bioactive constituents.
Among early findings from the LSU-Rutgers team are
- A beneficial effect, from a preparation of Russian tarragon, on carbohydrate metabolism in a mouse model of diabetes
- An effect (although weak), from a shilianhua extract, on glucose metabolism and insulin sensitivity in a mouse model of obesity
- Indications of an improvement, from an anthocyanin extract, on a number of measures of insulin sensitivity in a mouse model.
A Key Strategy
"We look forward to additional findings from the BRCs. These centers are an important part of NCCAM's effort to explore promising approaches and develop the evidence base for CAM and integrative medicine strategies to prevent and treat disease, maintain wellness, and improve quality of life," says Dr. Briggs.
NIH's other three Botanical Research Centers are the Center for Botanical Dietary Supplements Research in Women's Health, at the University of Illinois at Chicago College of Pharmacy; the Botanicals Research Center for Age-Related Diseases, at Purdue University; and the Center for Botanical Immunomodulators, at Memorial Sloan-Kettering Institute for Cancer Research. For brief profiles of all NCCAM's research centers, see nccam.nih.gov/training/centers/descriptions.htm.
References
- Birt DF, Widrlechner MP, LaLone CA, et al. Echinacea in infection. American Journal of Clinical Nutrition. 2008;87(2):488S–492S.
- Cefalu WT, Ye J, Zuberi A, et al. Botanicals and the metabolic syndrome. American Journal of Clinical Nutrition. 2008;87(2):481S–487S.
- Chilton FH, Rudel LL, Parks JS, et al. Mechanisms by which botanical lipids affect inflammatory disorders. American Journal of Clinical Nutrition. 2008;87(2):498S–503S.
- National Institutes of Health. Request for Applications (RFA) Number RFA-OD-04-002: Dietary Supplement Research Centers: Botanicals. Released December 22, 2003. NIH Guide for Grants and Contracts. Accessed at grants.nih.gov/grants/guide/rfa-files/rfa-od-04-002.html on May 20, 2008.
- Swanson CA, Liu QY. Introduction to the National Institutes of Health Botanical Research Centers program. American Journal of Clinical Nutrition. 2008;87(2):471S.
