An Efficient Method for the Large‐Scale Preparation of 3‐<i>O</i>‐Acetyl‐11‐oxo‐β‐boswellic Acid and Other Boswellic Acids

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.

show abstract

“…BAs were prepared as previously described (Jauch and Bergmann, 2003). All BAs and synthetic derivatives were at least 95% pure.…”

Section: Methodsmentioning

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

108

View full text Add to dashboard Cite

show abstract

“…This parallel previous findings for the reduction of the carbonyl group in the triterpene glycyrrhetinic acid 15,16 . The synthesis of 1 and 2 by hydrogenolysis of 3 or 4 seems more convenient than the previously reported reduction of 3 using powdered lithium in HMPA/tert-butanol 14,17 . Deacetylation of 2 or 4 afforded 1 or 3 in almost quantitative yield; acetylation of 1 or 3 furnished 2 and 4, respectively.…”

Section: Resultsmentioning

confidence: 88%

“…It was the merit of J. Jauch et al 14 to provide an easy access toAKBA (4); thereby the resin is extracted, and the crude extract is oxidized and acetylated. This sequence transformed all boswellic acids finally into AKBA (4).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and cytotoxic screening of beta-boswellic acid derivatives

et al. 2017

View full text Add to dashboard Cite

Beta-boswellic acids are triterpenoids being generic to the plants of genus boswellia. Although they were shown to exhibit different biological activities, the cytotoxic potential of b-boswellic acid derivatives remained by and large unexploited. To expand the potential of these compounds we developed simple procedures for the interconversion of the most important b-boswellic acids 1-4 and prepared several other derivatives 5-48. These compounds were screened for their cytotoxic activity in sulforhodamine B assays employing several human tumor cell lines and nonmalignant mouse fibroblasts. One of these compounds, a difluoromethylester of 3-O-acetyl-11-keto-beta-boswellic acid 23, was cytotoxic for human breast adenocarcinoma cells MCF-7 (EC50 = 6.5 mM) while being significantly less cytotoxic for the mouse fibroblasts.

show abstract

“…BAs were prepared as described previously (22). ␣-Amyrin was from Extrasynthèse; Boswellia serrata gum extract PS0201Bo was standardized to at least 1% KBA and 1% AKBA (quantified by reversed phase HPLC) and was provided by Pharmasan; EAH-Sepharose 4B, GE Healthcare Bio-Sciences; Abs against catG, BIOMOL; human catG, human tryptase, human chymase, human chymotrypsin, elastase inhibitor IV (N-(2-(4-(2,2-dimethylpropionyloxy)phenylsulfonylamino)benzoyl)aminoacetic acid) and 2-[3-{methyl[1-(2-naphthoyl)piperidin-4-yl]amino}carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid (JNJ-10311795), Calbiochem; human proteinase-3, Elastin Products; matrigel, BD Biosciences; trypsin (sequencing grade), Roche; all other fine chemicals were obtained by SigmaAldrich, unless stated otherwise.…”

Section: Methodsmentioning

confidence: 99%

Identification of Human Cathepsin G As a Functional Target of Boswellic Acids from the Anti-Inflammatory Remedy Frankincense

Tausch

Henkel

Siemoneit

et al. 2009

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Frankincense preparations, used in folk medicine to cure inflammatory diseases, showed anti-inflammatory effectiveness in animal models and clinical trials. Boswellic acids (BAs) constitute major pharmacological principles of frankincense, but their targets and the underlying molecular modes of action are still unclear. Using a BA-affinity Sepharose matrix, a 26-kDa protein was selectively precipitated from human neutrophils and identified as the lysosomal protease cathepsin G (catG) by mass spectrometry (MALDI-TOF) and by immunological analysis. In rigid automated molecular docking experiments BAs tightly bound to the active center of catG, occupying the same part of the binding site as the synthetic catG inhibitor JNJ-10311795 (2-[3-{methyl[1-(2-naphthoyl)piperidin-4-yl]amino}carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid). BAs potently suppressed the proteolytic activity of catG (IC50 of ∼600 nM) in a competitive and reversible manner. Related serine proteases were significantly less sensitive against BAs (leukocyte elastase, chymotrypsin, proteinase-3) or not affected (tryptase, chymase). BAs inhibited chemoinvasion but not chemotaxis of challenged neutrophils, and they suppressed Ca2+ mobilization in human platelets induced by isolated catG or by catG released from activated neutrophils. Finally, oral administration of defined frankincense extracts significantly reduced catG activities in human blood ex vivo vs placebo. In conclusion, we show that catG is a functional and pharmacologically relevant target of BAs, and interference with catG could explain some of the anti-inflammatory properties of frankincense.

show abstract

An Efficient Method for the Large‐Scale Preparation of 3‐O‐Acetyl‐11‐oxo‐β‐boswellic Acid and Other Boswellic Acids

Cited by 53 publications

References 18 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

Synthesis and cytotoxic screening of beta-boswellic acid derivatives

Identification of Human Cathepsin G As a Functional Target of Boswellic Acids from the Anti-Inflammatory Remedy Frankincense

Contact Info

Product

Resources

About

An Efficient Method for the Large‐Scale Preparation of 3‐O‐Acetyl‐11‐oxo‐β‐boswellic Acid and Other Boswellic Acids

Cited by 53 publications

References 18 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

Synthesis and cytotoxic screening of beta-boswellic acid derivatives

Identification of Human Cathepsin G As a Functional Target of Boswellic Acids from the Anti-Inflammatory Remedy Frankincense

Contact Info

Product

Resources

About

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