Modulation of the immune system by Boswellia serrata extracts and boswellic acids

Abstract 

Extracts from the gum resin of Boswellia serrata and some of is constituents including boswellic acids affect the immune system in different ways. Among the various boswellic acids 11-keto-β-boswellic acid (KBA) and acetyl-11-keto-β-boswellic acid have been observed to be active. However, also other boswellic acids may exhibit actions in the immune system.

In the humoral defence system a mixture of boswellic acis at higher doses reduced primary antibody titres; on the other hand lower doses enhanced secondary antibody titres following treatment with sheep erythrocytes.

In the cellular defence boswellic acides appear to increase lymphocyte proliferation whereas higher concentrations are even inhibitory. Moreover, BAs increase phagocytosis of macrophages.

BAs affect the cellular defence system by interaction with production/release of cytokines. Thus, BAs inhibit activation of NFκB which is a product of neutrophile granulocytes. Consequently a down regulation of TNF-α and decrease of IL-1, IL-2, IL-4, IL-6 and IFN-γ, which are proinflammatory cytokines by BEs and BAs has been reported.

Suppressions of the classic way of the complement system was found to be due to inhibition of the conversion of C3 into C3a and C3b. However, which of these pharmacological actions contribute to the therapeutic effects and which is finally the best dosage of a standardized extract needs further examination. And it is also a question whether or not a single BA will have the same therapeutic effect as a standardized extract.

Among the mediators of inflammatory reaction, mast cell stabilisation has been described by a BE. Inhibition of prostaglandin synthesis appears to play only a minor role as far as the anti-inflammatory effect is concerned.

On the other hand the inhibitory action of BAs on 5-LO leading to a decreased production of leukotrienes has received high attention by the scientific community since a variety of chronic inflammatory diseases is associatied with increased leukotriene activity.

At the end of the cascade of events in the cellular immune system as far as it directs to various tissues of the body – i.e. autoimmune diseases – formation of oxygen radicals and proteases (for example elastase) play an important destructive role. Here, BEs as well as BAs have been found to be inhibitory.

From the pharmacological properties of BEs and BAs it is not surprising that positive effects of BEs in some chronic inflammatory diseases including rheumatoid arthritis, bronchial asthma, osteoarthritis, ulcerative colitis and Crohn's disease have been reported.

Abbreviations: BS, Boswellia serrata, BE, Boswellic extract, BA, Boswellic acid, PFC, plaque-forming cell, LPS, lipopolysaccharides, PHA, phytohaemagglutinin, ConA, concanavalin A, NFκB, neutrophil factor κB, AKBA, acetyl-11-keto-β-boswellic acid, KBA, 11-keto-β-boswellic acid, TNF-α, tumor necrosis factor α, IL (1-12), interleukines 1-12, INF-γ, interferon-γ, PBMC_s, peripheral blood monocuclear cells, NK-cells, natural killer cells, C₃, complement 3, H₁-receptor, histamin 1-receptor, H₂-receptor, histamin 2-receptor, COX, cyclooxigenase, IKK, IκBαkinases, 5-HETE, 5-hydroxyeicosatetraenoic acid, 5-LO, 5-lipoxigenase, 12-HHT, 12-hydroxyheptadecatrienoic acid, fMLP, n-formyl-methionyl-leucyl-phenyl-alanin, FLAP, 5-lipoxigenase activating protein, HLE, human leucocyte elastase, LTB₄, leukotrien B₄, LTC₄, leukotrien C₄, LTD₄, leukotrien D₄, LTE₄, leukotrien E₄, NADPH, nicotinamid-adenin-dinucleotid-phosphat-hydrogen, PGF_1α, prostaglandin F 1α, PMA, phorbol 12-myristate 13 acetate, PMN, polymorphnuclear neutrophils, SOD, superoxiddismutase, TH1, T-helper cells

Keywords: Boswellia serrata extracts, Boswellic acids, Immune system