Essential oils are aromatic compounds produced naturally by plants. James Cook University scientists recently discovered a technique to apply natural plant extracts such as tea tree oil as a coating for medical devices. This process could prevent millions of infections every year. Professor Mohan Jacob, Head of Electrical and Electronics Engineering at JCU, and his team found that an increasing number of unplanned surgeries are being performed to fight infections mostly caused by bacterial activity on medical devices and a subsequent ‘biofilm’ forming on them. “Just in the U.S., about 17 million new biofilm-related infections are reported annually, leading to approximately 550,000 fatalities each year,” Jacob said. “It’s thought about 80 percent of worldwide surgery-associated infections may relate to biofilm formation.”
The team converted plant-based products – known as Plant Secondary Metabolites (PSMs) – into polymer coatings for medical devices, including implants. “They’re derived from such things as essential oils and herb extracts and they have relatively powerful, broad-spectrum antibacterial activities. PSMs are a low-cost, renewable resource available in commercial quantities, with limited toxicity, and potentially different mechanisms for fighting bacteria than synthetic antibiotics,” Jacob said. The group’s research also tackled the persistent problem of how to convert the plant extracts from a liquid to a solid state as a coating for medical devices without a significant loss of effectiveness.
Dr. Katia Bazaka is an Adjunct Senior Research Fellow and team member. “We used plasma-enhanced techniques within a reactor containing the essential oil vapors,” added team member Dr. Katia Bazaka, Adjunct Senior Research Fellow. “When the vapors are exposed to a glow discharge, they are transformed and settle on the surface of an implant as a solid biologically-active coating. These have shown good antibacterial properties. The main advantage of this approach is that we are not using other chemicals, such as solvents, during the fabrication process. As such, there is no threat of potentially harmful chemicals being retained in the coating or them damaging the surface of the material onto which the coating is applied. It also makes the fabrication process more environmentally friendly.”
Tea Tree Oil
The group is currently the global pioneers in the development of plant-derived polymer thin films – publishing over 70 research articles and six Ph.D. theses in the field. Professor Ian Atkinson, Director of JCU’s eResearch unit and a collaborator on the project, said the work had recently been extended to target marine organisms, to prevent the growth of biofilms on aquatic sensors and their subsequent failure. “Another attractive feature of these coatings is their optical transparency, which may be quite important if you are using them to coat contact lenses or optical windows in aquatic sensors,” he said.
Professor Jacob and his Ph.D. students are now collaborating with Dr. Peter Mulvey and Associate Professor Jeff Warner at the JCU-based Australian Institute of Tropical Health and Medicine to study the activity of different types of bacteria on the plant-based coatings. Even though synthetic antibiotics have been the best weapon for eradicating microbial infections since the arrival of penicillin, the overuse of these medications is gradually rendering them ineffective. Scientists think that if new strategies are not developed soon, medical treatments could retreat to the era where slight injuries and common infections develop into serious medical problems.
Most plants produce organic molecules as antimicrobial agents to combat harmful microorganisms. In the past few decades, progress in the synthesis of nanoscale materials, in particular plasma-assisted fabrication, has provided the means to retain the antimicrobial activities of plant secondary metabolites within bioactive coatings. Though the JCU team investigated many natural precursors, their main focus was on the Australian-based essential oil, tea tree oil and its components. As part of a Ph.D. project, Dr. Katia Bazaka developed antibacterial coatings from terpene-4-ol, which is a major component of tea tree oil.
Coconut Oil Benefits
Scientists from the University of Bonn, the German Center for Neurodegenerative Diseases and the German Cancer Research Center investigated such peroxisomal diseases on fruit flies. They were able to prove that a coconut oil diet significantly increases the vitality and lifespan of the flies. The results were presented in the journal PLOS Biology.
If the peroxisomes are damaged or absent, a toxic accumulation of very-long-chain fatty acids occurs. While science has so far primarily focused on these very-long-chain fatty acids as the cause of the disease, a research team around Dr. Margret Bülow at the LIMES Institute at the University of Bonn investigated the importance of medium-chain fatty acids. “These fatty acids are much more frequent than the very long-chain ones,” says Bülow. “Their importance has been underestimated so far.”
The research team used fruit flies as a classical model organism. The flies lacked a gene that encodes an important building block for the peroxisomes, which prevented the detoxification factories from working properly. The disease resembled peroxisome dysfunction in humans: Brain cells in the flies had died, so they could neither fly nor crawl. “What was striking about these animals was that they showed a medium-chain fatty deficiency,” reports lead author Dr. Julia Sellin. “It is precisely these fatty acids that serve as fuel for energy production in the cell power plants – the mitochondria.” It was therefore reasonable to assume that additional feeding with the deficient fatty acids could compensate for the damage.
A 1992 film drama told the true story of Lorenzo Odone, a seriously ill boy suffering from a peroxisomal disorder – a rare hereditary disease also known as adrenoleukodystrophy/ALD, which resulted in damage to the nervous system. The parents’ desperate search for treatment was turned into a film titled Lorenzo’s Oil, which made the disease well known. The disease arises from the dysfunction of so-called “peroxisomes.” These are tiny bubbles surrounded by a membrane that are mainly responsible for detoxifying the cells. In addition to harmful hydrogen peroxide, very-long-chain fatty acids in particular are also metabolized there.
Fruit Fly Findings
The scientists put some of the flies with the missing gene on a diet of coconut oil, which is rich in medium-chain fatty acids. A control group was fed conventionally. It was found that only about 20 percent of the fruit flies larvae raised on standard food developed further into adult specimens. Most of these died within 24 hours, while the normal life expectancy is around 40 to 50 days. In contrast, about 55 percent of the larvae fed with coconut oil produced adult fruit flies that survived for several weeks. “With the diet, the fruit flies suffering from the peroxisome disorder are able to survive, which is not possible on a conventional diet,” says Dr. Christian Wingen, the second lead author.
The damaged fly larvae showed symptoms of hunger stress. In the search for the causes, the team of researchers discovered lipase 3 – an enzyme that mobilizes fatty acids from the storage fat as fuel when there is a lack of food. Lipase 3 was upregulated to provide more energy. However, in peroxisome diseases the mitochondria are affected, which is why the fatty acids could not be completely processed and accumulated to a toxic amount. “This is probably the cause of death of the flies,” Bülow added. Another important role is played by “ceramide synthase Schlank,” which was discovered several years earlier at the LIMES Institute. If the synthase is outside the cell nucleus, lipase 3 is upregulated, which leads to the described damage. The coconut oil diet however dampened the increased activity of lipase 3, thereby reducing cell damage. A team of researchers led by Dr. Reinhard Bauer was recently able to show that Schlank is involved in the regulation of lipase 3.
Can the fruit fly findings be transferred to humans? The researchers also investigated human cell lines derived from patients with peroxisomal biogenesis disease. These too showed that without a coconut oil diet, the mitochondria swell and free fatty acids accumulate in toxic concentrations. “We were able to transfer some aspects that we observed on flies to human cells,” Bülow said. “This is an important indication for a possible therapy approach in humans, but there is still a lot of research to be done.”
Copaiba Oil Benefits
Sales of the essential oil copaiba are increasing, at least in part, because more than 54 million Americans suffer from some form of arthritis and 23.7 million are limited in their usual activity primarily due to pain. The conventional way to treat arthritis is using nonsteroidal, anti-inflammatory drugs (NSAIDs) as well as cyclo-oxygenase-2 inhibitors (COXIBs), which are not without adverse effects like gastrointestinal bleeding, heart attacks and stroke. For arthritis sufferers, copaiba may turn out to be a silver bullet or perhaps snake oil. The side effects of NSAIDs and COXIBs as well as warnings from the U.S. Food and Drug Administration on their risks of gastrointestinal side effects and bleeding as well as cardiovascular disease all suggest the need to test novel therapies with potential clinical benefits and fewer side effects than the available traditional medicines.
One such possible remedy is Copaifera reticulate or copaiba. The totality of evidence concerning the potential of copaiba to treat inflammatory arthritis is limited to basic research and uncontrolled clinical observations in humans. Researchers from Florida Atlantic University caution that randomized trials are necessary to discern whether the treatment is effective or that copaiba turns out to be yet another beautiful hypothesis slain by ugly facts. They present the incomplete totality of evidence and challenges in treating arthritis in their commentary published in the journal Integrative Medicine. “Copaiba is an essential oil that is used topically with little or no side effects, but there is insufficient evidence to judge whether it reduces pain and inflammation in patients with arthritis,” said Charles H. Hennekens, M.D., Dr.P.H., and senior author of the paper. “In case reports, individuals with joint pain and inflammation who used copaiba reported favorable results, however, this hypothesis is promising but as of yet unproven.”
Copaiba is a stimulant oleoresin obtained from the trunk of several pinnate-leaved South American leguminous trees found in the Amazon. Its medicinal usage dates back to the 16th century when natives of Brazil used it as folk medicine. Today, Brazil produces approximately 95 percent of this oil-resin, exporting more than 500 tons each year. “Basic research has suggested mechanisms of benefit of this essential oil in treating inflammatory arthritis,” says Hennekens. “Nonetheless, the only published data on copaiba on humans includes one case series and one small randomized trial of another inflammatory condition and not arthritis.”
The researchers conclude that the totality of the currently available evidence for copaiba essential oil is wholly insufficient to judge either its benefits or risks for the relief of pain and inflammation in arthritis. They emphasize that despite the absence of reliable evidence from large-scale randomized clinical trials, sales of copaiba continue to increase, presenting clinical and public health challenges. “To complete the totality of evidence, copaiba should be first tested in a randomized trial against a placebo in patients with inflammatory arthritis,” said Hennekens. “If such a trial shows a net benefit, then the next step would be direct randomized comparisons against NSAIDs and COXIBs.”
Orange Essential Oil Benefits
About eight percent of people will develop post-traumatic stress disorder at some point in their lives, according to the U.S. Department of Veterans Affairs, yet treatments for this debilitating condition remain limited. In a recent study, mice exposed to orange essential oil after a stressful situation showed improvements in markers of stress and fear, suggesting essential oil may offer a nonpharmaceutical option to help alleviate PTSD.
“Relative to pharmaceuticals, essential oils are much more economical and do not have adverse side effects,” says Cassandra Moshfegh, research assistant in Paul Marvar’s laboratory at the George Washington University. “The orange essential plant oil showed a significant effect on the behavioral response in our study mice. This is promising because it shows that passively inhaling this essential oil could potentially assuage PTSD symptoms in humans.” Orange essential oil is typically extracted from the peel of the orange fruit. People use essential oils for therapeutic purposes by diffusing them into the air, applying them to the skin or ingesting them in foods or beverages.
The researchers tested the effects of orange essential oil using Pavlovian Fear conditioning, a behavioral mouse model used to study the formation, storage and expression of fear memories as a model for PTSD. Mice were exposed to the orange essential oil by passive inhalation 40 minutes before and after fear conditioning. Typically mice freeze in fear when they hear a certain audial tone later, a response that diminishes gradually over time.
Twelve mice received the tone by itself, 12 mice received water and fear conditioning, and 12 mice received an orange essential oil and fear conditioning. Mice exposed to orange essential oil by passive inhalation showed a significant reduction in freezing behavior and stopped freezing earlier than the water-exposed, fear-conditioned mice. They also showed significant differences in the types of immune cells present after fear conditioning. The immune system contributes to the inflammation associated with chronic stress and fear, so immune cells are a marker of the biochemical pathways involved in PTSD.
Preliminary results point to differences in the gene expression in the brain between the mice that were exposed to essential oil and those that were not, hinting at a potential mechanism to explain the behavioral results. Moshfegh said further studies would be needed to understand the specific effects of orange essential oil in the brain and nervous system and shed light on how these effects might help to reduce fear and stress in people with PTSD