Toward a Natural
Product Remedy
for Arthritis and Rheumatoid Arthritis
A Combination of Traditional and New Cultures
One third of American adults use herbal capsules, tinctures, or teas seeking to improve their health and alleviate illness. Although widespread use of herbal products is relatively new in the U.S., it represents a $4 billion market. In many other cultures, notably Asian and Native American, herbal medicines have been successfully used over the centuries. The World Health Organization estimates that up to 80% of peoples in developing countries rely on indigenous traditional medicines to meet health care needs (Blumenthal, 1996). Arthritis and rheumatoid arthritis (RA) are diseases that have long been treated with traditional herbal remedies, especially in the Asian cultures.A joint research project conducted by Dr. Pannaman of the Biology Department at NJCU and the author (Chemistry Dept.) is currently underway to study the principle chemical components in several traditional Chinese medicinal plants (TCM) used to treat arthritis or rheumatoid arthritis. According to a report of traditional Chinese medicines, the Chinese people appear to be a healthy population and seem to do as well as those in the West in hospitals (Way, Liu, & Chen, 1996).
Arthritis is presently America’s number one cause of disability, affecting more than forty million Americans (Foster, 1997). The conventional treatments for arthritis are aspirin, corticosteroids, or nonsteroidal anti-inflammatory drugs (NSAIDS). However, undesirable side effects of NSAIDS drugs appear after prolonged usage. As many as 25 percent of prescription drugs contain an ingredient derived from higher plants. The replacement of many of the synthetic pharmaceutical compounds by natural substances is desirable because plant extracts are not subjected to the same rigorous testing procedures as synthetic analogues and are affordable to a broad spectrum of the population. Modified plant compounds proven to be effective against a particular ailment can also be chemically synthesized and mass-produced by the pharmaceutical industry. The synthesis of these compounds is important from an ecological perspective because the targeted plants are spared from over-exploitation and species endangerment.
Over a millennium, by trial, error, and serendipity, the Chinese have recorded the biological action of thousands of plant, animal, and mineral products. This has led to the use of a vast number of agents to diagnose, cure, and alleviate symptoms of ailments and illnesses. A Chinese medicinal information bank has been established showing a total of 240 plant families, 1,544 genera, and 4,940 species of vascular plants employed as medicines. Fifty-one percent of Chinese Solanaceae species, 47 percent of Cucurbitaceae species, and 45 percent of Rutaceae species are used in medicine (www.egregore.com/herb/ArthritisRheuma-
tism.htm; Lewis & Lewis, 1977). It is no wonder that the Chinese people consume considerable quantities of herbal remedies, many of which have been used for centuries. The problem is that ethnomedicines and the scientific bases for how they work are not well understood.The processes leading to inflammation are mediated by a variety of signaling molecules produced by cells of the immune system (Konig, Brom, Schonfeld, Knoller,& Stuning, 1987). Many Chinese herbs are prescribed by traditional practitioners to alleviate the inflammation associated with arthritis. We are using a Western approach to isolate and identify anti-inflammatory agents from TCMs. The reason is that a single component assures uniformity in response, minimizes drug interaction, and provides clues to the synthesis of superior analogues. In short, it allows us to specifically study what we think we are studying. One must always keep in mind that a decoction of eight plants could contain literally hundreds of different chemicals (Way, Liu, & Chen, 1996).
Much of this work involves fairly sophisticated, but routine, chemical instrumentation. In the past three years, the chemistry department has been equipping itself with the modern instrumentation that will allow it to carry out research on TCMs. Some work has already been completed on the isolation of chemical principles from two Chinese TCM’s, Chuan niu xi (Cyathula capitata) and Xi xian (Siegesbeckia orientalis L.). These plants are used by Chinese physicians to treat arthritis and rheumatoid arthritis (Duke & Ayensu, 1985).
We have optimized the separation and purification processes and are currently analyzing the plant extract fractions by various analytical instrumental techniques. The purification is accomplished by high-performance liquid chromatography (HPLC) which is used to separate a complex mixture into individual pure compounds. Once this is done (which is by no means a small feat), each individual chemical constituent can be identified by various spectroscopic techniques.
A very powerful technique that we have been using is gas chromatography-mass spectrometry (GC-MS). This technique separates components of a mixture where they appear as individual peaks on a chromatogram (shown below). The position is unique for a given chemical compound and the height of each peak is proportional to the amount of substance present. The chromatogram is from the plant Siegesbeckia orientalis L. with over thirty compounds represented in the mass spectrum. Each peak corresponds to a fragment-ion produced when a compound is bombarded with excess energy and produces what is called a fragmentation pattern. The numbers at the top of each peak correspond to unique fragment ions produced by this process. The identification of a compound is obtained from its overall mass spectral fragmentation pattern. Some of the individual compounds have been identified from their mass spectrum. We are currently working on the isolation of the individual compounds and will characterize these by GC-MS and nuclear magnetic resonance (NMR) spectroscopy.1
A crucial area of this research is the testing of these compounds for effectiveness in treating arthritis. This is not easy because of the limitations imposed on using animal or human subjects in biological assays. Recently, we have identified assays using animal cell lines instead of live animal models. We plan to expand our research efforts to include other Chinese, native American, and Indian medicinal plants.2
The activity of NSAIDS arises from inhibition of the enzymes cyclooxygenase 1 and 2 (COX-1 and COX-2) or the lipoxygenase enzymes (LOX). The COX enzymes are responsible for the formation of prostaglandins while the LOX enzymes initiates the leukotriene cascade from arachidonic acid.
COX-2 is induced by inflammatory stimuli such as cytokines (a protein) during the inflammatory process and is found mostly in cells that respond to inflammatory signaling molecules (Raguenes-Nicol, et al.,1999). It is believed that the gastrointestinal disturbances associated with NSAIDS result from inhibition of COX-1. Drug development has been directed toward finding drugs that are much more selective against the COX-2 enzyme (Miller, 1999). The lipoxygenase (LOX) enzymes are also implicated as an inflammatory component in disease states such as arthritis, asthma, allergy, and various skin diseases (Maycock, Pong, Evans, & Miller, 1989; Batt, 1992). Another important molecule recently associated with the inflammatory process is nitric oxide (NO) via an inducible form of the nitric oxide synthase (iNOS) enzyme. We are currently preparing biological assays that will test the principle compounds isolated from TCMs for toxicity and biological activity against the COX-2, LOX, and iNOS enzymes leading to the inflammatory and arthritic process.
REFERENCES
Batt, D.G. (1992). 5-Lipoxygenase inhibitors and their anti-inflammatory activities. Progress in Medicinal Chemistry, 29, 2-63.
Blumenthal, M. (1996). (Preface). In S. Foster, Herbs for your health (pp.vi-vii). CO: Interweave Press.
Duke, J. A., & Ayensu, E.S. (1985). Medicinal plants of China (Vol 2). Algonac, MI: Reference Publications.
Foster, S. (1997, February/March). No title. The Herb Companion, 69.
Konig, W., Brom, J., Schonfeld, W., Knoller, J., & Stuning, M. (1987). Effect of tenoxicam and indometacin on the release of histamine prostaglandin E2 and leukotrienes from various cells. Arzeimittel Forschung/Drug Research, 37 (1), 296-299.
Lewis, W.H., & Lewis, M.P.F. (1977). Medical botany. New York: Wiley.
Maycock, A.L.,Pong,S.,Evans,J.F., & Miller, D.K. (1989). In J. Rokach (Ed.), Leukotrienes and lipoxygenases (pp. 143-208). Lusanne, Switzerland:Elsevier Press.
Medicinal Herbs Online. (No date). Arthritis/Rheumatism, [Online]. Available: http://www.e gregore.com/herb/Arthritis Rheumatism.htm [2000, March 6].
Miller, D.R.(1999). Treatment options for rheumatoid arthritis. Drug Topics, 143(9), 53-62.
Raguenes-Nicol,C., Russo—Marie,F., Domage, G., Diab, N., Solito, E., Dray, F., Garcia-Mace, J.L., & Streichenberger, G. (1999). Anti-inflammatory mechanism of alminoprofen: Action on the phospholipid metabolism pathway. Biochemical Pharmacology, 57, 422-443, 1999.
Way,E.L., Liu,Y.Q.,& Chen, C.F. (1996). Perspective and overview of Chinese traditional medicine and contemporary pharmacology. Progress in Drug Research, 47, 131-164.
NOTES
1. Yamaguch, K. (1999, November 23). Enhancing the chemistry curriculum, teaching and research capabilities by the implementation of Fourier transform nuclear magnetic resonance (NPR) spectroscopy. Grant proposal., New Jersey City University, Jersey City, NJ, submitted to U.S. Department of Defense.
2. Yamaguchi, K. & Pannaman, L. (2000, January 9). Screening Chinese herbs for anti-rheumatic compounds. Grant proposal, New Jersey City University, Jersey City, NJ, submitted to U.S. Department of Health and Human Services (DHHS-PHS, AREA).
