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Study To Determine If Emu Oil
Showed Anti-Inflammatory,
Anti-Arthritic Activity In Laboratory Animals
Dr. Peter Ghosh
Royal North Shore Hospital, Sydney, Australia
Dr. Michael Whitehouse
University of Adelaide, Australia
1988
Summary:
Reported results from their experiments indicated that "the most potent formulation was achieved when methyl salicylate (wintergreen oil), isopropanol and menthol were combined with emu oil "Apparently, a synergistic effect was occurring between the emu oil and the methyl salicylate, for the anti-inflammatory activity of the combination was greater than the sum of either component when used alone (with isopropanol)."
Complete text:
Experimental Study to Determine the Anti-arthritic Activity of a New Emu Oil Formulation (EEMP) By Peter Ghosh, Ph D, F.R A.C.1., F.R.S.C, and Michael Whitehouse, D. Phil
BACKGROUND
While topically applied Emu Oil (EO) when combined with a suitable transdermal transporter had been demonstrated to show antiinflammatory activity in various rat models of inflammatory arthritis, its formulation with other antiinflammatory agents had not been investigated in any detail.
Our previous studies had shown that EO when combined with methyl ethyl, or isopropyl salicylate (MS) in the ratio (4.1 v/v) was more active than EO alone. However, the same EO preparation, when diluted (4.1 v/v) with isopropanol exhibited similar activity suggesting that the salicylates were only acting as transdermal transporters rather than contributing antiinflammatory activity. Subsequent studies indicated that cineole or eucalyptus oil when used at these same dilutions with EO were more effective than MS or isopropanol. Eucalyptus oil was therefore employed in our initial EO formulations.
Since isopropanol was known to be a well tolerated antiseptic rubefacient and MS had been incorporated into a number of efficacious OTC preparations by others, it was decided to evaluate a combination of these two compounds with EO in our study of arthritic rats. A small amount of menthol (2%) was also incorporated into the formulation as an antipruritic to overcome the potential skin irritant properties of MS.
METHODS
The classical polyarthritis rat model was used for the study. Male DA rats were injected subdermally in the base of the tail with M. tuberculosis/squaleneadjuvant on day one. Drug preparations and controls were applied to a shaved area on the dorsal skin 10, 11, 12, and 13 days later when the arthritis was well established. In these experiments EO and menthol were also tested when administered orally. The tail, rear and front paw swelling and weight of animals were determined daily for up to 17 days post-disease initiation. During the days 14-17 no drugs were applied and the change in paw swelling was used as an index of "rebound of disease" after cessation of drug treatment. The colour and tone of the skin where drugs were applied was also monitored as an index of irritancy. Six rats were used in each group and the mean increase in swelling were determined.
RESULTS
As evident in the Table(table is not included here) in animals in which no drugs were applied, considerable swelling of both rear and front paws was observed. The magnitude of this effect declined in the 14-17 day period.
The EMMP formulation at 3. O ml/kg almost abolished this paw swelling, however on terminating application (days 14-17) the inflammation (swelling) rebounded. A control formulation, OMMP using olive oil in place of EO in the formulation was inactive confirming that MS and menthol were not effective without EO in this severe arthritis model. Furthermore, some skin irritancy was evidenced in using the OMMP formulation. EO-cineole was less active than EMMP and EO given orally was inactive.
CONCLUSION
The EMMP formulation appears from the present experiments to be more potent than when EO was formulated with cineole. This combination was used previously. Since MS, when combined with olive oil - menthol and isopropanol was inactive, it would appear that synergisms of the EO and MS antiinflammatory activities was achieved in the EMMP formulation. The mechanisms responsible for this apparent synergism has yet to be determined.
ANTI-RHEUMATIC ACTIVITY OF EMU OIL
Although Emu Oil and fat have been used for the treatment of arthritis and rheumatism by the Aboriginal people for thousands of years, it was not until white settlement that it's therapeutic effects were first documented. Early explorers and bushmen extolled the merits of Emu oil as an embrocation for relief of a number of ailments, including rheumatism, lumbago, and joint stiffness. However, controlled laboratory based-scientific studies had never been undertaken to support these anecdotal claims. In 1988, there was a conjoint research project which was initiated between Dr. Michael Whitehouse, Department of Pathology, University of Adelaide, South Australia, and Associate Professor Peter Ghosh, Royal North Shore Hospital, Sydney, New South Wales, to determine if Emu oil showed antiinflammatory antiarthritic activity in laboratory animals. Both Dr. Whitehouse and Associate professor Ghosh had been engaged in arthritis research for over 25 years and have published extensively on the evaluation and development of new antiarthritic drugs.
The classical method of assessing whether a compound had antiarthritic and/or antiinflammatory activity is by means of the rat polyarthritis model. The arthritis in this model is induced by injecting dead bacteria in a dispersant into the base of the rat tails. Over the next few weeks the tails and paws swell due to the inflammation caused by the reaction of white cells to the dead bacteria. Drugs under examination can be administered to the rat, orally, topically or by injection to determine if they can reduce the joint swelling which would indicate that they exhibited antiinflammatory activity.
When Emu oil alone was rubbed onto the shaved backs of the arthritic rats, the antiinflammatory response was not that strong. It was reasoned by the researchers that the low activity could be due to the thickness of the oil which was hindering its penetration through the rat�s skin. This explanation was vindicated by subsequent experiments in which the Emu oil was "thinned out" by solvents, such as isopropanol or ethyl acetate. When such mixtures were applied topically to the rats, almost complete remission of swelling was achieved with several days of application. After testing a wide variety of different thinners of the oil, it was discovered that the combination with Eucalyptus oil afforded a good antiinflammatory formulation in the rat arthritis model. However, the most potent formulation was achieved when methyl salicylate(oil of wintergreen), isopropanol, and menthol(from oil of peppermint) were combined with emu oil. The experimental studies showed that a synergistic effect was occurring between the Emu oil and methyl salicylate, for the antiinflammatory activity of the combination was greater than the sum of either component when used alone (with isopropanol). This new formulation is currently being evaluated under controlled clinical trial conditions in arthritic patients in Perth, however, the results of open studies are so far encouraging.
The pharmacological researchers have now joined forces with analytical chemists (Dr. Michael Dawson and Aethol Turner) at the University of Technology, Sydney, in order to identify the compounds in Emu oil which could be responsible for its remarkable biological properties. Research to-date, has established that the structures of the active principles are complex, but the team is optimistic that they can come up with the answer before the end of 1993.
Peter Ghosh, Ph.D., F.R.A.C.I., F.R.S.C. Raymond Purves Research Laboratories Royal North Shore Hospital of Sydney, Australia Michael Whitehouse, D.Phil. (Oxon) Department of Pathology University of Adelaide, Australia PETER GHOSH - CURRICULUM VITAE - SYNOPSIS Qualifications: B. Sc. (Hons), Kings College, University of London ( 196 l ) Ph.D., University of East Angila, UK ( l 966) F.R.A.C.I. (Australia) (1975) F.R.S.C. (UK) (1989) Academic Appointments: Director of above Director (Acting), Bone and Joint Foundation, Research Foundation, University of Sydney Associate Professor, Department of Surgery, University of Sydney Main Honorary Executive Positions 1991: Member, Medical Research Council, RNSH Deputy Director, Science Council, RNSH Board Member, SpineCare Foundation Member, Medical and Scientific Advisory Committee, SpineCare Foundation Member, Scientific Advisory Comrnittee, Osteogenesis Imperfecta Society of NSW
Faculty of Medicine Large Equipment Advisory Comrnittee, University of Sydney Executive Comrnittee, OrthopaedicResearch Society of Australia and NewZealand Advisory Committee, Osteoarthritis Research Society (Paris)
Scientific Assessor/Reviewer for Grants and Journals:
National Health and Medical Research Council, Australian Research Grants Cornmittee, Medical Research Council of New Zealand, Australian Orthopaedic Association, Australian Rheumatism Association, UtahFoundation (USA), Arthritis Society (Canada), US-Israel Binational Science Foundation, Veteran Affairs, Journal of Rheumatology, Rheumatology International, Australian Journal of Biological Sciences, Agents and Actions, Seminars in Arthritis and Rheumatism.
International Pharmaceutical Company Consultantships (1990/91): Roussel UCLAF, Paris, France Luitbold-Werk Munich, FRG Fidia SPA, Abano Terme, Italy Seikagaku Corporation, Tokyo, Japan Pharmacdia AB, Uppsala, Sweden Greenwich Pharmaceuticals, USA Society Membership/Positions:
Orthopaedic Research Society (US) (elected full-member,1978); New York Academy of Science (elected full-member,1982); Australian Orthopacdic Association (affiliate member 1988); Australian Rheumatism Association (associate member, 1975); Royal Society of Chemistry (associate 1963, and fellow member, 1989); Royal Australian Chemical Institute (fellow 1975); AustralianBiochemical Society (member 1972); Connective Tissue Society ANZ (Treasurer,1978-83), President, (1983-85); Australian Society of Medical Research (member 1971); Australian Society of Experimental Pathology (member, 1973); Orthopaedic Research Society of Australia - New Zealand (executive member); Osteoarthritis Research Society (executive member).
Invitations to Speak/Chair at National/lnternational Scientific Meetings = 49 Publications: (a) 169 (Books, Reviews, Editorials, Monographs, Journal articles) (b) 268 Abstracts of Scientific Meetings Teaching: PostgraduateResearch Students Supervised (1970-91)M.Sc. = 5; Ph.D. = 14;M.D. = 2 ExternalPhD./M.Sc. Thesisexamined(1970-90)= 10 Rheumatology Registrant Training Program (Lecturer/Advisor) Guest Lecturer, University of Technology, Sydney (Gore Hill)
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