NATIONAL PARKINSON FOUNDATION, INC.

1501 N.W. 9th Avenue / Bob Hope RoadMiami, Florida 33136-1494 Beans (MucunaPruriens) For Parkinsons Disease:An Herbal Alternative
Bala V. Manyam, M.D., NPF Center of Excellence Plummer Movement Disorders Center Department of NeurologyGlenn R. Cryer, Scientific Publications and Biomedical CommunicationsScott & White Clinic and Texas A&M University Health Science System College of Medicine Temple, Texas Parkinsons disease drugs like most other drugs used today, are chemicals synthesised in the laboratory and then manufactured. Making drugs in the laboratory is a slow, expensive and tedious process. This is one reason in plants and other natural sources but only five percent of them have been explored to-date. Plant based drugs for Parkinsons disease, include L-DOPA containing sources such as the seeds of Mucuna pruriens (Figure 1 : Mucuna pruriens plant showing pods) and Vincia faba, the same chemical compound that has been used for Parkinsons disease in the last 30 years. Seeds of Datura stramonium have an anticholinergic effect, similar to Artane and Cogentin. Banisterine from Banisteria caapi and Nicotiana tabacum has monoamine oxidase inhibitor that is similar to selegiline (deprenyl). In this article, we will discuss more about Mucuna pruriens. Before explaining how the powder from the Mucuna pruriens plant is being used as an alternative therapy, it should be noted that Parkinsons disease affects more than one million people in the U.S. alone, and new and effective treatments for this particular disease are goals of many researchers. Parkinsons disease is a degenerative neurological disease that primarily impacts the part of the brain that produces dopamine, a chemical substance that allows neurologic impulses to be sent from one terminal end of a nerve cell to the beginning of another nerve cell terminal. In Parkinsons disease, however, there is not enough dopamine produced by the brain for its needs. The simple act of walking may not be so simple. The disease can effect the body in many ways. The most common symptoms of the disease include trembling (shaking), stooped posture, muscular stiffness, short shuffling steps, speaking softly and rapidly, poor balance, poor handwriting, and of course, slowness of body movements. The cause of the disease is not known, however, a variety of medications can control the symptoms. Physicians in ancient India first used Mucuna seeds in the treatment of Parkinsons disease over 4500 years ago. The Indian medical system is called Ayurveda, which is the worlds oldest system of medicine based on scientific principles. Ayurveda is founded on scientific principles. It has a long history of use of herbal remedies and has documented data on mechanism of action, specific action, short-term and long-term toxic effects, drug-drug and drug-diet interaction with a long history of use in humans. As per historical evidence, Parkinsons disease existed in ancient India and was called Kampavata.

This was over 4500 years ago even though the disease acquired its present name from James Parkinson who redescribed the disease in 1817 A.D. In the Ayurvedic system, powder of Mucuna is used for treating Parkinsons disease and is subjected to special processing. The English name "cowage" plant (Mucuna pruriens) is derived from Hindi Kiwach. In Sanskrit, it is called Atmagupta. Mucuna is a twiner with trifoliate leaves, purple flowers, and turgid S-shaped pods covered with hairs that cause intense itching on contact with the skin. The plant belongs to the family Leguminosae, which is indigenous to India and has long been used in Ayurveda since ancient times. Overdose effects of Mucuna were also recognized in Ayurveda. These included headache, dystonia, fatigue, tremor, syncope, and thirst. Many of these could also occur from synthetic L-DOPA. In the modern times, two Indian scientists isolated L-DOPA from Mucuna in 1936 and published their results. However, at that time the role of L-DOPA in Parkinsons was not known, hence not much attention was given to the discovery. Subsequently, when dopamine deficiency was linked to Parkinsons disease in the 1960s, scientists got interested in finding a source of L-DOPA for treatment of Parkinsons disease. Because, the presence of L-DOPA was known to be present in the legume, initial attention was paid to extract levodopa from various Mucuna seeds and in fact, over a thousand plants were screened for the high content of L-DOPA. As L-DOPA was synthesized, further work on extraction of L-DOPA from beans was abandoned. The amount of Mucuna powder used by Ayurvedic physicians was small compared to the amount of synthetic LDOPA used to produce the same benefit; if one looks at the amount of L-DOPA alone. This is what led to one of the authors (BVM) to further study how such a small quantity of levodopa in Mucuna could have helped and thought possibly that there could be other undiscovered drugs in Mucuna that may enhance either the activity of L-DOPA such as carbidopa as seen in Sinemet or there may be an independent compound in Mucuna that may have a direct effect on symptoms of Parkinsons disease. This idea led to collaboration between Drs. Manyam with Dr. K. M. Parikh, President of the Zandu Pharmaceutical Works, a leading Ayurvedic manufacturing company located in Bombay, India. Their team conducted a series of experiments to establish and to develop a drug for Parkinsons disease from Mucuna (Figure 2 : Mucuna beans with skin (left), beans with skin removed (right) and powder). The initial work required making the drug from Mucuna palatable. They developed a preparation and named it HP200, which is a powder form and has to be mixed with water just before administration. This is the first "liquid levodopa" preparation ever made. They also established that when mixed with water the preparation Figure 2 remained stable for several hours. The powder was also tested so that there was no loss of active compounds during storage. Despite the fact Mucuna was used in the treatment of Parkinsons disease in ancient times, it is still important today to establish that the drug dose not have adverse effects on various vital organs. This was accomplished by administering low to very high doses of the drug in rats and rabbits and testing the effect of Mucuna on blood Bala Manyam, M.D. V.

chemistry and blood count (such as the one that many physicians perform in their offices and the hospitals) and various organs. Some of the tests were done for as long as one year and the results indicated no adverse effects were present from Mucuna preparations. To establish how Mucuna would compare to synthetic L-DOPA, experiments were undertaken in animal models of Parkinsons disease. Two different doses of synthetic L-DOPA and two different doses of Mucuna were administered making sure that the amount of L-DOPA present is the same in Mucuna as was the doses of synthetic L-DOPA. The effects of the drugs were tested using a specially designed instrument called "Rotometer." Dose for dose, Mucuna was two to three times more effective than equivalent amounts of synthetic L-DOPA. This suggests that Mucuna may contain compounds that make L-DOPA function better such as carbidopa, tolcapone (Tasmar), or entacapone (COMTan). It may also suggest that Mucuna independently improve symptoms of Parkinsons disease. Although quite encouraging, more research is needed to confirm these findings. This work was done at the time when the United States Congress established the Office of Alternative Medicine in the National Institute of Health and the work was one of the first to receive funding for alternative medicine. Additional studies in India were undertaken to establish the benefit of HP200 in patients with Parkinsons disease. Four medical centers were selected involving sixty patients and several neurologists. The studies were conducted for three months. During that time, the patients received HP200 while no concomitant L-DOPA preparations were administered. Trained neurologists monitored changes in the degree of patents symptoms and any side effects. At the end of the study, it was determined that the HP200 was highly beneficial in the treatment of Parkinsons disease. The side effects were minimal. HP200 was approved by the Indian Food and Drug Administration and is available in India under the brand name Zandopa. Further, the cost of the drug was much cheaper compared to the synthetic drugs; thus it became more affordable to the patients. The United States Food and Drug Administration approve the drug for clinical studies, however, it is not available from the pharmacist. Work on the Mucuna for Parkinsons disease is being continued. The importance of this particular study is not that Mucuna is an alternative to L-DOPA, rather it is that compounds occurring naturally in plants for example, may contain biologically active components that can be isolated, tested, and used to provide safer and better treatments for Parkinsons disease.