Boswellic Acids in Chronic Inflammatory Diseases

Ammon, H. P. T.

doi:10.1055/s-2006-947227

Cited by 256 publications

(185 citation statements)

References 46 publications

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“…Pilot clinical studies indicated some therapeutic efficacy of frankincense, mainly in OA and RA (Ammon, 2006;Sengupta et al, 2008). Clinical studies using 5-LOX inhibitors (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…The pentacyclic triterpenes boswellic acids (BAs; Figure 1) are assumed to be the pharmacological active principles of frankincense extracts, and based on data obtained from experiments using cellular and animal models (Poeckel and Werz, 2006), there is accumulating evidence for anti-inflammatory and anti-tumorigenic effects of BAs. Pilot clinical studies have suggested some efficacy of frankincense preparations in the treatment of osteoarthritis (OA), rheumatoid arthritis (RA), inflammatory bowel diseases, asthma and cancer (see Ammon, 2006;Poeckel and Werz, 2006). Molecular mechanisms responsible for these therapeutics effects have been mainly attributed to the interference of 3-O-acetyl-11-keto-b-BA (AKBA) with signalling pathways including the nuclear factor-kB route (Syrovets et al, 2005), mitogen-activated protein kinase pathway and Ca 2+ signalling (Poeckel et al, 2006a) as well as targeting human leukocyte elastase (HLE) (Safayhi et al, 1997), 5-lipoxygenase (5-LOX) (Safayhi et al, 1992), platelet-type 12-lipoxygenase (12S-LOX) (Poeckel et al, 2006b) and COX-1 .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Siemoneit

Koeberle

Rossi

et al. 2010

British J Pharmacology

109

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BACKGROUND AND PURPOSEFrankincense, the gum resin derived from Boswellia species, showed anti-inflammatory efficacy in animal models and in pilot clinical studies. Boswellic acids (BAs) are assumed to be responsible for these effects but their anti-inflammatory efficacy in vivo and their molecular modes of action are incompletely understood. EXPERIMENTAL APPROACHA protein fishing approach using immobilized BA and surface plasmon resonance (SPR) spectroscopy were used to reveal microsomal prostaglandin E2 synthase-1 (mPGES1) as a BA-interacting protein. Cell-free and cell-based assays were applied to confirm the functional interference of BAs with mPGES1. Carrageenan-induced mouse paw oedema and rat pleurisy models were utilized to demonstrate the efficacy of defined BAs in vivo. KEY RESULTSHuman mPGES1 from A549 cells or in vitro-translated human enzyme selectively bound to BA affinity matrices and SPR spectroscopy confirmed these interactions. BAs reversibly suppressed the transformation of prostaglandin (PG)H2 to PGE2 mediated by mPGES1 (IC50 = 3-10 mM). Also, in intact A549 cells, BAs selectively inhibited PGE2 generation and, in human whole blood, b-BA reduced lipopolysaccharide-induced PGE2 biosynthesis without affecting formation of the COX-derived metabolites 6-keto PGF1a and thromboxane B2. Intraperitoneal or oral administration of b-BA (1 mg·kg -1 ) suppressed rat pleurisy, accompanied by impaired levels of PGE2 and b-BA (1 mg·kg -1 , given i.p.) also reduced mouse paw oedema, both induced by carrageenan. CONCLUSIONS AND IMPLICATIONSSuppression of PGE2 formation by BAs via interference with mPGES1 contribute to the anti-inflammatory effectiveness of BAs and of frankincense, and may constitute a biochemical basis for their anti-inflammatory properties.

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“…Pilot clinical studies indicated some therapeutic efficacy of frankincense, mainly in OA and RA (Ammon, 2006;Sengupta et al, 2008). Clinical studies using 5-LOX inhibitors (i.e.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Siemoneit

Koeberle

Rossi

et al. 2010

British J Pharmacology

109

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“…11 In clinical research, positive effects of boswellic acids in the treatment of inflammatory diseases could be shown. 3,12 There exist clinical trials about the use of boswellic acids in asthma, 13 rheumatoid arthritis, 14 Crohn disease, 15 collagenous colitis, 16 and osteoarthritis of the knee. 17,18 To our knowledge, there exist only first clinical observation results for the treatment of cerebral edema by boswellic acids.…”

Section: Discussionmentioning

confidence: 99%

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

Kirste

Treier

Wehrle

et al. 2011

Cancer

116

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BACKGROUND:Patients irradiated for brain tumors often suffer from cerebral edema and are usually treated with dexamethasone, which has various side effects. To investigate the activity of Boswellia serrata (BS) in radiotherapyrelated edema, we conducted a prospective, randomized, placebo-controlled, double-blind, pilot trial. METHODS: Forty-four patients with primary or secondary malignant cerebral tumors were randomly assigned to radiotherapy plus either BS 4200 mg/day or placebo. The volume of cerebral edema in the T2-weighted magnetic resonance imaging (MRI) sequence was analyzed as a primary endpoint. Secondary endpoints were toxicity, cognitive function, quality of life, and the need for antiedematous (dexamethasone) medication. Blood samples were taken to analyze the serum concentration of boswellic acids (AKBA and KBA). RESULTS: Compared with baseline and if measured immediately after the end of radiotherapy and BS/placebo treatment, a reduction of cerebral edema of >75% was found in 60% of patients receiving BS and in 26% of patients receiving placebo (P ¼ .023). These findings may be based on an additional antitumor effect. There were no severe adverse events in either group. In the BS group, 6 patients reported minor gastrointestinal discomfort. BS did not have a significant impact on quality of life or cognitive function. The dexamethasone dose during radiotherapy in both groups was not statistically different. Boswellic acids could be detected in patients' serum. CONCLUSIONS: BS significantly reduced cerebral edema measured by MRI in the study population. BS could potentially be steroid-sparing for patients receiving brain irradiation. Our findings will need to be further validated in larger studies. Cancer 2011;117:3788-

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“…The pentacyclic triterpenes (PTs) are widely distributed among plants and, due to the complex biosynthesis including cyclization of squalene, only higher plants able to carry out this catalysis contain PTs. Many plants containing PTs, in particular boswellic acids (BAs) from Boswellia serrata, have been used as anti-inflammatory remedies in folk medicine (for review see [152], [153]). …”

Section: Pentacyclic Triterpenesmentioning

confidence: 99%

“…The most-recognized PTs that act on 5-LO are BAs, and many studies addressed the respective molecular interactions (for detailed review see [153], [156]). BAs with an 11-keto moiety, preferably 3-O-acteyl-11-keto-b-BA (AKBA 89, Table 6) are of particular interest, and AKBA 89 is the most efficient derivative with IC 50 values 1.5 ± 15 mM in intact cells [74], [154], [157], [158], [159].…”

Section: Pentacyclic Triterpenesmentioning

confidence: 99%

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

Werz¹

2007

Planta Med

153

135

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The biosynthesis of leukotrienes (LTs) is initiated by the transformation of free arachidonic acid to LTA 4 by 5-lipoxygenase (5-LO). Subsequent enzymatic conversion of LTA 4 yields LTB 4 and the cysteinyl-LTs C 4 , D 4 and E 4 . LTs have prominent functions in pathophysiology and are connected to numerous disorders including bronchial asthma, allergic rhinitis, inflammatory bowel and skin diseases, rheumatoid arthritis, cancer, osteoporosis and cardiovascular diseases. Pharmacological and genetic interruption of the 5-LO pathway or blockade of LT receptors, serving as means for intervention with LTs, may be of therapeutic value for certain related disorders. Natural or plant-derived substances were among the first 5-LO inhibitors identified in the early 1980 s. To date, a huge number of diverse plant-derived compounds have been reported to interfere with 5-LO product synthesis. However, many investigations have addressed the efficacy of a given compound solely in cellular test systems and analysis of direct interference with 5-LO has been neglected. In the first part of this review, the biology and molecular pharmacology of the 5-LO pathway is summarized in order to understand its overall regulation and complexity as well as to comprehend the possible points of attack of compounds that eventually lead to inhibition of 5-LO product formation in intact cells. In the second part, natural compounds that interfere with 5-LO product formation are compiled and grouped into structural classes, and the underlying molecular mechanisms and structureactivity relationships are discussed.

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Boswellic Acids in Chronic Inflammatory Diseases

Cited by 256 publications

References 46 publications

Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

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Boswellic Acids in Chronic Inflammatory Diseases

Cited by 256 publications

References 46 publications

Inhibition of microsomal prostaglandin E2 synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Inhibition of microsomal prostaglandin E2 synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

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Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense