Nature Did it First
(October 25th, 2013) In the past, clever chemists have used all their skills to develop a drug that effectively treats pain. But Mother Nature had the same idea a long, long time ago. Recently, researchers discovered that a widely prescribed pain killer exists in its natural state in an African tree.
In the modern day, the use of pharmaceutical agents is on an incline. Approximately 1.5 billion people across the world suffer from some form of chronic pain; the value of the global pharmaceutical industry is expected to rise to $ 60 billion (ca. € 45 billion) by 2015. In this climate, previously relied upon herbal remedies are being cast aside as ‘old wives tales’. However, a recent publication suggests that there may be more to these herbal remedies than previously thought.
The African pincushion tree, Nauclea latifolia, has long been used by native healers to treat a number of ailments including pain, fever and digestive problems. Extracts from the plant are also thought to be an effective treatment for parasitic infections. The research of a French-Swiss-Cameroonian collaboration, involving Michel De Waard from the Joseph Fourier University in Grenoble, has delved deep into the therapeutic properties of this plant and identified that extracts from the root bark, commonly used by traditional African healers in medicating the sick, contains none other than the analgesic compound tramadol.
The study began by collecting specimens of N. latifolia root bark and fractionating the chemical compounds within, in the hope of identifying the active compounds responsible for the medicinal properties previously observed. The efficacy of each compound against nociception - the sensation of pain - was examined in mice, and the most effective antinociceptive compound was analysed further. The inhibitory effect of this compound on the pain response was found to be comparable to that of other common pain killers, including morphine and aspirin. To determine the crystal structure of the compound responsible for this effect, X-ray crystallography was required, and revealed that this naturally occurring analgesic was biochemically identical to the man-made drug, tramadol.
Tramadol is a widely-used analgesic compound, which is marketed under more than 55 brand names worldwide. This drug works in a manner similar to that of other opioids, such as morphine and codeine, which bind to the opioid receptor, μ, and block the transmission of the pain message to the brain. The end result is a feeling of euphoria and a decreased perception of pain. In addition, tramadol can also prevent the reuptake of the neurotransmitters serotonin and noradrenaline, allowing these feel-good compounds to remain at the synapse, continuing to transmit signals, for a prolonged period, in a manner similar to that of many anti-depressants. It has been suggested that the dual mechanisms of action of this drug results in a lower number of side-effects experienced by patients. In addition, tramadol has a reduced risk of dependency, and is therefore often preferred over other pain killers such as Vicodin® and morphine, which are highly addictive.
While this is not the first incidence of a synthetic drug being found to be naturally occurring, the authors believe their work to be unique in that this compound, unlike the others, is found at clinically relevant concentrations. The authors identified that natural tramadol accounted for approximately 0.4% of the dried root extract. While this appears to be a rather small amount, the researchers were able to produce 200 mg of tramadol, at a purity of more than 95%, from 20g of dried root extract powder. The normal starting dose for a patient is 25 mg per day, before titrating up to a daily dose of 100 mg for more severe pain. When questioned about the potential uses of these findings, Michel De Waard explained that he does not envisage that natural tramadol is likely to replace the synthetic form any time soon. However, he does believe that large-scale production of this compound, to complement the current pharmaceutical market, is a distinct possibility.
The researchers now plan to investigate other African Nauclea species to determine exactly which contain tramadol. They conclude that this investigation can be used to aid patients in their use of these extracts and propose that the plant may be considered a readily-available and inexpensive form of the drug. Perhaps there is more to some herbal remedies than the placebo effect that some sceptics would have us believe.
Photo: Nauclea latifolia Sm./Stefan Dressler from: Brunken, U., Schmidt, M., Dressler, S., Janssen, T., Thiombiano, A. & Zizka, G. 2008. West African plants - A Photo Guide. www.westafricanplants.senckenberg.de. - Forschungsinstitut Senckenberg, Frankfurt/Main, Germany.