One of the consequences of aging is a reduction in the effectiveness of the immune system.
The decline of the immune system is accompanied by an increase in inflammatory signals which can negatively impact many of the body’s normal functions. When you are young, your body fights infection by producing T-cells which are able to adapt to the infection and fight it off.
As you age or your immune system becomes otherwise compromised, such as in patients with auto-immune conditions or obesity, the body is less able to produce the same types of T-cells. The mechanisms by which the body attempts to compensate for this includes increasing the inflammatory response and releasing a cytokine called interleukin-6 (IL-6).
Higher levels of IL-6 are associated with a greater risk of death and there is evidence that IL-6 is involved in the development of certain chronic inflammatory disorders. Levels are especially high in patients with auto-immune conditions or chronic inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease.
IL-6 is one of the main signaling pathways implicated in aging and chronic morbidity
Levels of IL-6 increase with age and are associated with many of the ‘symptoms’ of aging. “Elevated serum IL-6 is positively associated with markers of physical frailty such as low walking speed, poor muscle strength (94), poor lower extremity performance (95), and anemia” (Marcello et al, 2006). “Levels of circulating IL-6 are elevated in several inflammatory diseases including RA (as mentioned above), systemic juvenile idiopathic arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriasis and Crohn’s disease” (Gabay, 2006).
Drugs have been developed to combat the effects of IL-6. Tocilizumab, an antibody that blocks IL-6 function by binding to the IL-6 receptor, has been approved for the treatment of Rheumatoid Arthritis.
Inhibiting IL-6 with natural substances
The Boswellia serrata plant is native to the dry habitats of India, Northern Africa, and the Middle East. The gummy resin of this tree, also known as frankincense, contains compounds which have been used for their anti-inflammatory and pain relieving effects since the times of ancient Egypt. In ayurvedic medicine, boswellia has been utilized for arthritis, dysentry, ringworm, diarrhea, and pulmonary diseases.
New research into the Boswellia resin has shown that boswellic acids are powerful inhibitors of pro-inflammatory molecules, and may prove to be more effective than NSAIDs.
Boswellic acids are a known 5-LOX inhibitor, and have also been found to be an inhibitor of IL-6 both in vivo and in vitro.
“Frankincense [Boswellia] nutraceuticals significantly inhibited the release of proinflammatory cytokines, such as TNF-α, IL-6, and IL-8 […] Moreover, boswellic and lupeolic acid contents correlated with TNF-α, IL-1β, IL-6, IL-8, and IL-10 inhibition” (Schmiech et al, 2019).
Administration of BS [Boswellia] (200 and 400 mg/kg) also significantly downregulat-ed (p < 0.05) TNF-α,IL-1β,IL-6,NF-κB, and Bax mRNA expression (Pengzong et al, 2019).
Boswellic acid inhibits the production of pro-inflammatory cytokines, including TNF-α, IL-1, IL-2, IL-6, IL-12, and IFN-γ, by suppressing the activation of NF-κB (Gayathri et al., 2007).
It is likely that Boswellia’s IL-6 inhibiting action is due to it’s ability to inhibit 5-LOX. Multiple studies have demonstrated that treatment with various 5-LOX inhibitors results in reduced IL-6 secretion (Pihlaja et al, 2017)(Lin et al, 2014).
Sharma, S., Gupta, S., Khajuria, V., Bhagat, A., Ahmed, Z., & Shah, B. A. (2016). Analogues of boswellic acids as inhibitors of pro-inflammatory cytokines TNF-α and IL-6. Bioorganic & medicinal chemistry letters, 26(2), 695–698. https://doi.org/10.1016/j.bmcl.2015.11.035
Marcello Maggio, Jack M. Guralnik, Dan L. Longo, Luigi Ferrucci. (2006). Interleukin-6 in Aging and Chronic Disease: A Magnificent Pathway, The Journals of Gerontology: Series A, Volume 61, Issue 6, Pages 575–584, https://doi.org/10.1093/gerona/61.6.575
Gabay C. (2006). Interleukin-6 and chronic inflammation. Arthritis research & therapy, 8 Suppl 2(Suppl 2), S3. https://doi.org/10.1186/ar1917
Schmiech, M., Lang, S. J., Ulrich, J., Werner, K., Rashan, L. J., Syrovets, T., & Simmet, T. (2019). Comparative Investigation of Frankincense Nutraceuticals: Correlation of Boswellic and Lupeolic Acid Contents with Cytokine Release Inhibition and Toxicity against Triple-Negative Breast Cancer Cells. Nutrients, 11(10), 2341. https://doi.org/10.3390/nu11102341
Gayathri, B., Manjula, N., Vinaykumar, K. S., Lakshmi, B. S., & Balakrishnan, A. (2007). Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFalpha, IL-1beta, NO and MAP kinases. International immunopharmacology, 7(4), 473–482. https://doi.org/10.1016/j.intimp.2006.12.003
Pihlaja, R., Haaparanta-Solin, M., Rinne, J. (2017). The Anti-Inflammatory Effects of Lipoxygenase and Cyclo-Oxygenase Inhibitors… Frontiers in Neuroscience. https://www.frontiersin.org/article/10.3389/fnins.2017.00299
Lin, H. C., Lin, T. H., Wu, M. Y., Chiu, Y. C., Tang, C. H., Hour, M. J., Liou, H. C., Tu, H. J., Yang, R. S., & Fu, W. M. (2014). 5-Lipoxygenase inhibitors attenuate TNF-α-induced inflammation in human synovial fibroblasts. PloS one, 9(9), e107890. https://doi.org/10.1371/journal.pone.0107890
Pengzong, Z., Yuanmin, L., Xiaoming, X., Shang, D., Wei, X., Zhigang, L., Dongzhou, D., Wenjing, Y., Jianbiao, Y., Yang, X., & Xia, L. (2019). Wound Healing Potential of the Standardized Extract of Boswellia serrata on Experimental Diabetic Foot Ulcer via Inhibition of Inflammatory, Angiogenetic and Apoptotic Markers. Planta medica, 85(8), 657–669. https://doi.org/10.1055/a-0881-3000