Incense has been literally sacred for millennia. As can now be seen, an ingredient in frankincense resin actually has an almost magical effect: Boswellic acid converts an endogenous protein that normally promotes inflammation into a version with an inhibitory effect. The substance therefore has potential for the development of anti-inflammatory drugs, the scientists say.
The most famous appearance of incense in the New Testament: In addition to gold and myrrh, the three kings gave incense to the baby Jesus. This story shows how precious the resin of the Boswellia trees was at that time. For millennia, frankincense was of medical importance in many different cultures in addition to cult. This was based on effects that have now been scientifically proven and are increasingly becoming the focus of research: “The resin obtained from the frankincense tree contains anti-inflammatory substances that make it suitable, among other things, for the treatment of diseases such as asthma, rheumatoid arthritis or neurodermatitis”, says Oliver Werz from the Friedrich Schiller University in Jena.
On the track of the mechanism of action
Werz and his team have been researching the anti-inflammatory potential of frankincense resin for several years. As they report, the so-called boswellic acid has emerged as the mastermind of this effect. In their current study, they were able to elucidate the interesting mode of action of this substance. As they report, boswellic acid affects the action of a protein that plays a key role in the development of inflammatory processes in the body: 5-lipoxygenase. “It has been known for more than 40 years that this enzyme promotes the formation of leukotrienes, an important group of inflammatory messengers in the human body,” explains Werz.
As part of their study, the scientists initially succeeded in elucidating the structure of 5-lipoxygenase and presenting it in detail using modern computer modeling methods. As they explain, the structural information not only illuminates the enzyme, but also its possible interactions with certain active ingredients. The researchers can now show how inhibitors bind to the enzyme and which molecular complexes are formed. They carried out corresponding analyzes with the synthetic anti-inflammatory agent Zileuton and with natural substances that also have potential as active ingredients. This included the boswellic acid from the frankincense.
Molecular transformative power
As Werz and his colleagues report, she was surprised by the unusual binding behavior of boswellic acid: while zileuton and the other active substances docked directly in the active center of the enzyme and thus inhibited its inflammation-promoting function, a completely different picture emerged with boswellic acid at a point away from the center with the enzyme. As the researchers were able to show, this unusual binding also causes structural changes in the active center, which inhibits enzyme activity. However, this only proved to be part of the principle of action of the frankincense substance.
“The influence of boswellic acid goes well beyond this effect,” says co-author Jana Gerstmeier. “The binding creates a domino effect, which also changes the specificity of the enzyme,” explains the scientist. The analyzes of the molecular complex and its possible effects show that 5-lipoxygenase reverses its function under the influence of boswellic acid: Instead of triggering the formation of inflammatory leukotrienes, 5-lipoxygenase then produces anti-inflammatory substances, the modeling shows. “In simple terms, this means that the frankincense ingredient re-programs the inflammatory enzyme into an inflammation-resolving enzyme,” says Gerstmeier.
As the scientists explain, their findings now have potential for the development of anti-inflammatory drugs that are suitable for the treatment of asthma, rheumatoid arthritis or neurodermatitis. By elucidating the protein structure of 5-lipoxygenase, various potential drugs could now be identified and their effectiveness as an anti-inflammatory drug tested. The researchers now want to further explore the suitability of frankincense boswellic acid as a drug. So the power of the ancient remedy could possibly specifically alleviate inflammatory reactions.
Source: Friedrich Schiller University Jena: Nature Chemical Biology, doi: 10.1038 / s41589-020-0544-7