What is inflammation?
Inflammation is a defensive response by our body to stimuli such as allergens or injury to the tissue and is how our immune system mounts an effective defence against invading pathogens. However, uncontrolled inflammation is a major contributory factor for disorders such as allergies, cardiovascular problems, metabolic syndrome, cancer and the autoimmune diseases. Not only are these conditions a source of suffering for individuals but can also impose an economic burden on the person as well as society.
Chronic levels of inflammation also accompany the aging processes leading to a range of diseases. Keeping excessive inflammation levels down is therefore an important strategy in maintaining health and longevity.
There are a huge range of drugs and medicines available for controlling or suppressing excessive inflammatory response. Nonsteroid anti-inflammatory drugs (NSAIDs) and immunosuppressants are examples of commonly used approaches to treat excessive inflammatory responses but they often come with unpleasant or even dangerous side effects.
This has led some researchers to search for alternatives in nature and to mine the natural world for compounds and substances that may reduce inflammation without the side effects already known drugs have. For that reason traditional medicines have been the focus of modern research efforts with a number of herbs and extracts used for centuries turning out to have some very interesting properties indeed. It should really be no surprise considering the majority of modern drugs and medicines are all based on compounds originally found in nature.
Rosmarinic acid anti-inflammatory extraordinaire
Polyphenols are well known for their antioxidant properties and many of them also have anti-inflammatory effects too. Rosmarinic acid is a naturally occurring polyphenol and is no exception to this. No surprise then that the herb and its extract has been used in the traditional medicines of various cultures.
An open label trial assessed patients with osteoarthritis and rheumatoid arthritis given an extract containing rosmarinic acid over the course of four weeks (1). The researchers discovered that the hs-CRP (an index showing the presence of inflammation) had been decreased significantly in patients taking the supplement. There was also a decrease in the level of C-reactive protein, another biomarker for the presence of inflammation, in those patients who had elevated levels of CRP prior to the experiment. There were also no serious side effects observed.
Further evidence for the anti-inflammatory potential of rosmarinic acid was shown another study (2). It was shown that rosmarinic acid was able to disturb complement system activation by inhibiting C3b bonding and the dose was very low to do this. C3b is an essential part of the innate immune system and excessive levels of this can result in diseases such as atypical hemolytic uremic syndrome (aHUS), hemolytic disorders, and certain autoimmune disorders. Current standard of care is
treatment with the complement-inhibitory anti-C5 monoclonal antibody, eculizumab or similar. Rosmarinic acid presents a potential alternative approach to achieve similar reduction of C3b to manage these conditions.
Rosmarinic acid has also shown gastroprotective action against gastric ulcers, even more effective than commonly used Omeprazole (3). It is more effective because of its ability to inhibit neutrophil infiltration and it is able to reduce proinflammatory mediators, in particular TNF-a and IL-1 which are both involved in inflammatory responses and can lead to excessive inflammation when levels are too high. This could mean that rosmarinic acid could be a better solution to such conditions.
Rosmarinic acid could also have possible application in aiding wound healing (4). In a study the topical application of extract of rosemary was tested on diabetic mouse models to see if it would influence wound healing. The results indicated that the essential oil of rosemary, a traditional Jordanian medicine, was active in healing diabetic wounds and supports the use of rosmarinic acid for treating wounds.
A further study demonstrated the anti-inflammatory properties of rosmarinic acid in both localized inflammation and systemic inflammation in rats (5). For local inflammation they induced paw edema and for systemic inflammation using liver ischemia-reperfusion and thermal injury models. In the local inflammation model, the researchers discovered that 25 mg/kg of rosmarinic acid or extract of rosemary reduced paw edema by over 60% in just six hours. There was a dose-response effect suggesting that rosmarinic acid is the main active ingredient contributing to the anti-inflammatory effect.
In the liver ischemia-reperfusion model, rosmarinic acid given at 25 mg/kg prior to injury led to a significant reduction of transaminases AST and ALT. Commonly the transaminases alanine transaminase (ALT) and aspartate transaminase (AST), are indicative of liver damage. The researchers also noted that there was also a reduction of systemic lactate dehydrogenase levels. LDH is expressed by body tissues, such as blood cells and heart muscle. It is released during tissue damage, and for this reason it is a common biomarker for tissue injuries and diseases such as heart failure and liver damage.
Finally in the thermal injury tests, rosmarinic acid given at 25 mg/kg five minutes prior to injury significantly reduce multiple organ (liver, kidney, lung) dysfunction biomarkers. It did this by modulating NF-κB and metalloproteinase-9.
The NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) protein complex controls transcription of DNA, cytokine production and cell survival and is also a master regulator of the immune response. As we age NF-κB levels rise systemically leading to excessive immune reactions and chronic inflammation that drives the aging process. Metalloproteinase-9 is involved in a variety of functions including bone development, wound healing, cell migration but also pathological processes, such as arthritis and cancer metastasis.
This study showed that rosmarinic acid has direct and powerful anti-inflammatory properties that could be useful in wound healing and controlling inflammation caused by injuries.
And recently a study investigated the potential anti-inflammatory effects of Rosemary (Rosmarinus officinalis) and rosmarinic acid in a rat model of sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain to confirm the efficacy of rosemary in traditional medicine use.
Two rat test groups were treated with either Rosmarinus officinalis (400 mg/kg) extract or rosmarinic acid (40 mg/kg) after CCI was induced. The researchers examined the anti-inflammatory effects of both preparations by looking at inflammatory biomarkers including cyclooxygenase-2 (COX2), prostaglandin E2 (PGE-2), interleukin 1 beta (IL-1β), matrix metallopeptidase 2 (MMP2), and nitric oxide (NO) production.
The researchers showed that both Rosmarinic acid and extract of Rosmarinus officinalis were able to reduce levels of all the biomarkers noted above. This supports the use of Rosmarinus officinalis as an effective remedy for pain relief and inflammation. It also suggests that extract of Rosmarinus officinalis and rosmarinic acid through modulating inflammation are potential candidates for treating neuropathic pain and other similar neurological disorders associated with inflammation.
Rosmarinic acid shows a great deal of potential for mediating the inflammatory immune response and could be useful for treating injuries, diseases and as a way to keep inflammation down to optimize health.
(1) Lukaczer, D., Darland, G., Tripp, M., Liska, D. A., Lerman, R. H., Schiltz, B., & Bland, J. S. (2005). A Pilot trial evaluating meta050, a proprietary combination of reduced iso‐alpha acids, rosemary extract and oleanolic acid in patients with arthritis and fibromyalgia. Phytotherapy Research, 19(10), 864-869.
(2) Sahu, A., Rawal, N., & Pangburn, M. K. (1999). Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b. Biochemical pharmacology, 57(12), 1439-1446.
(3) Amaral, G. P., de Carvalho, N. R., Barcelos, R. P., Dobrachinski, F., de Lima Portella, R., da Silva, M. H., … & Athayde, M. L. (2013). Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats. Food and Chemical Toxicology, 55, 48-55.
(5) Abu-Al-Basal, M. A. (2010). Healing potential of Rosmarinus officinalis L. on full-thickness excision cutaneous wounds in alloxan-induced-diabetic BALB/c mice. Journal of ethnopharmacology, 131(2), 443-450.
(6) Rocha, J., Eduardo‐Figueira, M., Barateiro, A., Fernandes, A., Brites, D., Bronze, R., … & Fernandes, E. (2015). Anti‐inflammatory Effect of Rosmarinic Acid and an Extract of Rosmarinus officinalis in Rat Models of Local and Systemic Inflammation. Basic & clinical pharmacology & toxicology, 116(5), 398-413.
(7) Rahbardar, M. G., Amin, B., Mehri, S., Mirnajafi-Zadeh, S. J., & Hosseinzadeh, H. (2017). Anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. and rosmarinic acid in a rat model of neuropathic pain. Biomedicine & Pharmacotherapy, 86, 441-449.