A-Boswellic acid

The survival of a-boswellic acid, p-boswellic acid and their O-acetates, which have been isolated only from frankincense, has been demonstrated in archaeological samples [99,107,113]. These compounds are considered as very useful specific chemical markers for the identification of frankincense in resinous archaeological materials. 

Figure 8.3 Mass spectra of (a) a boswellic acid, (b) (3 boswellic acid and (c,d) their O acetates in the form ofTMS derivatives... 

Boswellic acids are constituents of incense (olibanum) from Boswellia serrata and B. carterii (Burseraceae) a-boswellic acid incorporates the 12-oleanene core structure (section 6.3.3), while 12-ursene is the parent hydrocarbon of p-boswellic acid and ketoboswellic acid. Various derivatives of boswellic acids are reported to have antiinflammatory properties and therefore are suggested to be potential cortisone substitutes. 

Contains 3-1% volatile oil 60-70% resins composed mainly of 3-acetyl-P-boswellic acid and a-boswellic acid about 20% gum made up of galactose, arabinose, and 4-0-methylglucuronic acid 5-8% bassorin and bitter substances (jiangsu list and horhammer). ... 

E.-R. Sailer, S. Schweizer, S. E. Boden, H. P. T. Ammon, H. Safayhi, Characterization of an acetyl-11-keto-a-boswellic acid and arachidonate-binding regulatory site of 5-lipoxygenase using photoaffinity labeling, Eur.. Biochem. 1998. 256,364-368. 

The GC-MS data (Figure 16.11) of the violet zone of B. carterii revealed that the unchanged diterpenes (verticillatriene, cembrene A, and cembrene C) and the nortriterpenes with carbohydrate structure originated from the pyrolyzed triterpenes (Figure 16.12) of the a- and (3-boswellic acids, named 24-norursa-3,12-diene (compound 7), 24-norursa-3,9(ll),12-triene (compound 8), 24-noroleana-3,12-diene (compound 9), and 24-noroleana-3,9(ll),12-triene (compound 10). 

Frankincense, also known as olibanum, is obtained from trees belonging to the genus Boswellia (Burseraceae family). It is one of the best-known ancient plant resins. The ancient Egyptians were the first to use it as incense in embalming practices and in the preparation of medicines, cosmetics and perfumes, and today it is still used therapeutically. It contains pentacyclic triterpenoids belonging to oleanane, ursane or lupane type molecules and in particular of a- and p-boswellic acids, and their O-acetates [104 111], 11 -Oxo-p-boswellic acid and its acetyl derivative, identified in several Boswellia species, are also diagnostic for frankincense [112]. 

Bose-Einstein condensation, 17 352 Bosons, 17 352 Boswellic acids, 24 557 Botox (Clostridium botulinum toxin type A), 2 816 Bottle centrifuge operation, 5 528-529 theory of performance, 5 507-508 Bottle polymerizatioi, 20 376 Bottles... 

Several examples of bioassay-guided isolation are given in the literature. Recio et al [47] used a topical irritant agent to track the activity during the isolation of the anti-inflammatory triterpenes from Diospyros leucomelas, whereas Cuellar et al. [48] employed a combined system of in vivo and in vitro experiments, consisting of the inhibition of an enzyme activity Fig. (1) . Other authors prefer in vitro models. Ammon and Safayhi [49] used the inhibition of leukotriene formation in rat peritoneal neutrophils to isolate the boswellic acids of gum resin exudate of Boswellia serrata, whereas Takaishi et al. [42] studied the inhibition of interleukin-1 secretion, and Jain et al. [50] studied the in vitro inhibition of phospholipase A2 activity. The main results of these studies are summarised in the pharmacological activity section of this chapter. 

In washed human platelets, NDGA inhibited the formation of 12-LOX products as well as the COX product 12-hydroxyheptadecatrienoic acid (12-HHT), with an IC50 of 5 pM, while boswellic acids (mixture of a- and P-isomers) at concentrations up to 400 pM exerted no effect. In addition, in a cell-free system, the non-enzymatic peroxidation of AA by iron (II)-ascorbate was not affected by boswellic acid at concentrations up to 400 pM, whereas NDGA abolished the peroxidation of AA in this test at a concentration of 10 pM. These results suggest that the activity of boswellic acids is selective in the 5-LOX pathway, and the mechanism of inhibition is different from that of the classic antioxidant 5-LOX inhibitors (NDGA, caffeic acid, quercetin) [96]. 

The structural requirements of boswellic acid type 5-LOX inhibitors for selective bindings to the effector site and for enzyme inhibitory activity have recently been reported by Sailer et al [97]. Saponification of AKBA yielded 11-keto-P-boswellic acid with a free 3a-OH function. This deacetylation slightly diminished the 5-LOX inhibitory potency in intact cells and in a cell free system. A minor decrease in 5-LOX inhibitory activity was found to be caused by a reduction of the carboxyl function of 11-keto-P-boswellic acid to a primary alcohol function. This yielded an 11-keto diol-triterpene, which was still able to inhibit 5-LOX activity. 

The boswellic acid derivative, AKBA, decreases the activity of HLE in vitro in a concentration-dependent manner, with an IC50 value of 15 iM. This result has been compared with those obtained with ursolic acid, amyrin and 18p-glycyrrhetinic acid, the last of which showed no inhibitory activity on HLE at concentrations up to 20 pM [105]. Data analyses indicate different mechanisms for the inhibitory actions of the pentacyclic triterpenes AKBA and ursolic acid inhibition is noncompetitive in the case of AKBA but competitive with ursolic acid. These results are in line with the hypothesis that pentacyclic triterpenes interact with the extended substrate-binding domain in HLE that can bind a variety of hydrophobic ligands [104]. Depending on the substrate length, HLE inhibition can be competitive (ursolic acid) or non-competitive (AKBA). 

In summary, HLE inhibition has been established for different compounds, but a dual HLE/5-LOX inhibitory property is characteristic of the pentacyclic triterpenes from the boswellic acid series. Although alternative mechanisms of action may contribute to the anti-inflammatory action of pentacyclic triterpenes, these compounds can serve as parent compounds for a new class of HLE inhibitors. 

Some of the best known anti-inflammatory triterpenoids have been shown to have inhibitory activity on the complement cascade. A mixture of the aforementioned boswellic acids reduced in a dose-dependent manner the classic pathway activity by as much as 77%, and C3-convertase by 72% [118]. Oleanolic acid showed 85% and 71% inhibition, respectively, in the same tests, at a single dose of 100 jxg/ml [119], and P-glycyrrhetinic acid inhibited the classic human pathway with an IC50 of 35 xM. The component affected was C2. The a form of glycyrrhetinic acid was fairly inactive [120]. None of these three triterpenoids appreciably inhibited the alternative complement pathway. 

Brill E, Haimematm F, Zapp J, Bruening G, Jauch J, Bernhardt R (2014) A new cytochrome P450 system from Bacillus megaterium DSM319 for the hydroxylation of 11-keto-heto-boswellic acid (kba). Appl Microbiol Biotechnol 98 1703 1717... 

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