(Commerce)—An annual festival in the northeast Texas town of Commerce celebrates the inedible, wrinkled green fruit of the bois d'arc tree, and now scientists have given the town another reason to fete the humble fruit—it may help combat Alzheimer's disease.
Researchers at Texas A&M University-Commerce are investigating how a class of chemicals found in the native northeast Texas plant is capable of blocking the toxic effects of a compound known to play a role in Alzheimer's.
The fruit of the bois d'arc tree (pronounced BO-dark), also known as Osage orange or locally as a bois d'arc apple, contains high levels of natural chemicals called isoflavones. Research has indicated that consumption of isoflavone compounds, which are found in dietary plants such as soybeans, may play a role in lowering one's risk for heart disease and cancer, ease menopause symptoms and improve bone health.
"When people talk about the positive effects, such as cancer prevention, of eating soy and fruits and vegetables, those benefits are usually ascribed to antioxidant and/or estrogenic compounds such as isoflavones," said William Whaley, assistant professor of chemistry at A&M-Commerce speaking from the university's new $28-million state-of-the-art Science Building, which is to be dedicated Tuesday, April 4. The facility also includes a world-class planetarium, which opened to the public in February.
Isoflavones from both soy and the Osage orange recently have been demonstrated by other laboratories to protect brain cells, or neurons, from the toxic effect of amyloid beta peptide, which is believed to be responsible for the degeneration of neurons in Alzheimer's patients. However, the precise mechanisms by which isoflavones block the toxicity of amyloid beta peptide are unknown.
Soybeans contain less than one-tenth of 1 percent isoflavone compounds, Whaley said. By comparison, between 5 percent and 10 percent of the dry mass of a bois d'arc apple is composed of isoflavone compounds.
"This plant has somehow developed the ability to produce extraordinary high levels of isoflavone compounds," Whaley said. "There is no known dietary plant that contains this high level of isoflavones."
The bois d'arc apple is an inedible, wrinkly-surfaced, light-green colored fruit that contains a sticky, latex rubber-like substance. Commerce, known as the "Bois d'arc Capital of Texas," holds an annual Bois d'arc Bash, which includes a parade, street fair, foot race and car show. Native to northeast Texas, southeast Oklahoma and southwest Arkansas, the hard wood of the bois d'arc, or "bow wood," was used by Native Americans for bows and arrows. The tree was one of the first new species described by Lewis and Clark on their historic journey.
While horses often eat the fruit, the isoflavones in the Osage orange would probably cause stomach irritation in humans due to their phenolic character. Salicylic acid, which is a phenolic compound isolated from willow bark, also caused severe stomach irritation; however, this compound led to the discovery of aspirin, which is one of the most widely sold pharmaceuticals in the world.
"Ingesting a large amount of this material would not be wise; it would probably make you sick," Whaley said. "At the same time, the chemical compounds produced by this fruit may have potentially important biological activities that we are just beginning to understand."
Whaley's research is focused on determining the molecular structure of the unique kind of isoflavones found in the Osage orange and on identifying the enzymes, and the genes that encode them, that are responsible for producing these compounds. Once the genes are identified and cloned, it may be possible to insert these genes into other, more palatable dietary plants, or forage plants eaten by livestock, he said.
"There are different kinds of isoflavones, each with their own unique structure," Whaley said. "The ones in the Osage orange have a peculiar structure that makes them very water insoluble. But they could be used as precursors in the chemical synthesis of other ingestible isoflavones."
Whaley is particularly interested in how isoflavones protect brain cells from the toxic effects of the amyloid beta protein, which travels through the blood stream by hitching a ride within low-density lipoprotein, or LDL, particles. Whaley's recent research has focused on how isoflavones get inside, or partition into, lipid structures called micelles. These micelles are simple lipid structures that are chemically similar to LDL particles.
To study the mechanisms for how isoflavones get inside the LDL particles in the body, Whaley has used micelles as a simple model. He adds a special detergent to water that forms micelles, and by adding isoflavones to the mix, he can then observe how the isoflavones position and orient themselves within the micelle structure. The position and orientation of isoflavones is a key consideration in understanding how they protect lipid structures from reactive oxygen species, which are also called free radicals. It is the reactivity of free radicals that ultimately is responsible for the aging process.
"The next step is to take the techniques we've developed for studying detergent micelles and translate those techniques into more complex models and eventually into cells," he said. "The mechanism by which isoflavones block neurotoxicity could be related to their ability to lodge into lipid membranes, because that is where the precursor to amyloid beta peptide is usually located. Understanding the basic structure of the isoflavones and their interaction with lipid structures hopefully will give us insight into how natural chemicals in fruits and vegetables may lower the risk for developing diseases such as Alzheimer's disease or atherosclerosis.
"Coming up with a magic bullet to treat Alzheimer's disease is a long way off, but I think there's a chance of learning something through natural products such as the isoflavones produced by Osage orange. They probably will not provide an immediate drug, but understanding their biological activities may indicate an avenue of research for developing a new pharmaceutical."
Whaley's studies of organic compounds will be enhanced with a new piece of equipment, a 400 megahertz (MHz) nuclear magnetic resonance (NMR) spectrometer due to arrive on campus this spring. The device enables researchers to study the detailed structure and behavior of large organic molecules such as isoflavones. Several research groups on campus will use the instrument, Whaley said.
"This is a very important tool in studying the structure and function of natural products, which often have complicated structures," Whaley said. "An instrument of this quality is really a unique piece of equipment to have at a university this size, and especially important to our students, who will be exposed to an NMR spectrometer of the type they may encounter in industry or in academic research."
The spectrometer will be housed in the new Science Building, a three-story, 110,000-square-foot research and classroom facility that is home to physics, chemistry, and biological and environmental sciences.