Research Highlights from 1990 to 1997

Inhibition by boswellic acids of human leukocyte elastase

Safayhi H, Rall B, Sailer ER, Ammon HP J Pharmacol Exp Ther. 1997 Apr;281(1):460-3

The present study focused on the anti-inflammatory effects of frankincense extracts. The leukotriene formation and human leukocyte elastase (HLE) release were observed to be increased simultaneously by neutrophil stimulation in a variety of inflammation- and hypersensitivity-based human diseases. In the current study, acetyl-11-keto-β-boswellic acid, a direct, non-redox and non-competitive 5-lipoxygenase inhibitor, showed inhibition effects on the activity of HLE (IC50 = 15 microM). Similarly, a substantial HLE inhibition activity was shown by other pentacyclic triterpenes viz., β-boswellic acid, amyrin and ursolic acid, except 18-β-glycyrrhetinic acid. These results suggest that the dual inhibition of 5-lipoxygenase and HLE is unique to boswellic acids. Because, though ursolic acid and amyrin are the pentacyclic triterpenes with HLE inhibitory activity they did not show 5-lipoxygenase inhibition. The blockade of two pro-inflammatory enzymes, 5-lipoxygenase and HLE might be the rationale for the putative antiphlogistic activity of acetyl-11-keto-β-boswellic acid and other boswellic acid derivatives.


Effects of Boswellia serrata gum resin in patients with ulcerative colitis

Gupta I, Parihar A, Malhotra P, Singh GB, Lüdtke R, Safayhi H, Ammon HP Eur J Med Res. 1997 Jan;2(1):37-43

The study investigated the effects of B. serrata gum resin preparation (300 mg three times a day for 6 weeks) in patients with grade II and II ulcerative colitis. The patients treated with B. serrata gum resin preparation had improved stool properties, histopathology and scan microscopy of rectal biopsies, hematological parameters, serum iron, calcium, phosphorus as well as proteins comparable to the control group treated with sulfasalazine (1 g TID).


Acetyl-11-keto-β-boswellic acid (AKBBA): structure requirements for binding and 5-lipoxygenase inhibitory activity

Sailer ER, Subramanian LR, Rall B, Hoernlein RF,
Ammon HP, Safayhi H Br J Pharmacol. 1996 Feb;117(4):615-8

The study had investigated the effects of natural pentacyclic triterpenes and their derivatives on 5-lipoxygenase activity. The results have demonstrated that the pentacyclic triterpene ring is crucial for binding to a highly selective effector site, whereas the functional groups on the ring viz., C11 carbonyl functional group along with C4 hydrophilic group are essential for 5-lipoxygenase inhibitory activity.


Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-β-boswellic acid

Safayhi H, Sailer ER, Ammon HP Mol Pharmacol. 1995 Jun;47(6):1212-6

The study explored the mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-β-boswellic acid (AKBBA). It had reported that the inhibition of 5-lipoxygenase by AKBBA was not due to non-specific lipophilic interactions because the lipophilic four-ring compounds neither inhibited the activity of the 5-lipoxygenase nor antagonized the inhibitory action of AKBBA. The study concluded that AKBBA acts directly on the 5-lipoxygenase enzyme at a certain site for the pentacyclic triterpenes that is different from the arachidonic acid binding site.


Application of papaya latex-induced rat paw inflammation: Model for evaluation of slowly acting antiarthritic drugs

Gupta OP, Sharma N, Chand D J Pharmacol Toxicol Methods. 1994 Apr;31(2):95-8

Drugs such as aspirin, indomethacin, piroxicam, ibuprofen, prednisolone, levamisole, chloroquine, boswellic acids showed anti-inflammatory activity in papaya latex-induced rat paw inflammation model. levamisole, chloroquine, Boswellic acids are known as slowly acting anti-arthritic drugs. The current study had evaluated in detail the sensitivity of this model for clinically effective, slowly acting, anti-arthritic drugs viz. levamisole, chloroquine, penicillamine, aurothioglucose, cyclophosphamide, as well as boswellic acids. the study had concluded suggesting drugs that display significant activity in the papaya latex model would be identified as slowly acting antiarthritic drugs.


Recent progress in the study of anticancer drugs originating from plants and traditional medicines in China

Han R Chin Med Sci J. 1994 Mar;9(1):61-9

This review is about plant-derived drugs that are used in the prevention and treatment of cancer. Anticancer drugs originating from plants and traditional medicines in China are discussed with particular emphasis on taxol, daidzein, acetyl boswellic acid, curcumin, and ginsenoside Rh2.


Highlight on the studies of anticancer drugs derived from plants in China

Han R Stem Cells. 1994 Jan;12(1):53-63

The present study is a review of the anticancer drugs originating from plants in China. Some of the drugs that are explained in this include indirubin, airisquinone, 10-hydroxy camptothecin, ginsenoside Rh2, curcumin, daidzein, acetyl boswellic acid, harringtonine, homoharringtonine, and taxol. The search for new plant-based anticancer drugs will be a fruitful frontier in cancer treatment and chemoprevention.


Mechanism of antiinflammatory actions of curcumine and boswellic acids

Ammon HP, Safayhi H, Mack T, Sabieraj J J Ethnopharmacol. 1993 Mar;38(2-3):113-9

This report had explored in vitro the mechanisms for anti-inflammatory beneficial effects of curcumine from Curcuma longa and the gum resin of Boswellia serrata. Curcumine was found to inhibit 5-lipoxygenase, 12-lipoxygenase and cyclooxygenase activities. Whereas, boswellic acids, the active principles from gum resins of B. serrata inhibited only 5-lipoxygenase. Further, boswellic acids lack the inhibition of peroxidation compared to curcumin. These results suggest that boswellic acids may be specific and nonredox inhibitors of leukotriene synthesis by directly interacting with the 5-lipoxygenase enzyme.


Anti-complementary activity of boswellic acids: an inhibitor of C3-convertase of the classical complement pathway

Kapil A, Moza N Int J Immunopharmacol. 1992 Oct;14(7):1139-43

In this study, Boswellic acids (BA) exhibited anticomplementary activity and showed inhibition of antibody-coated sheep erythrocyteimmunohemodialysis, in vitro at a threshold concentration of 100 micrograms. However, the higher concentrations of BA showed constant inhibitory effects on immunohaemolysis. Further, BA also showed the inhibitory effect on guinea-pig serum upon in vivo administration.


A sensitive and relevant model for evaluating anti-inflammatory activity-papaya latex-induced rat paw inflammation

Gupta OP, Sharma N, Chand D J Pharmacol Toxicol Methods. 1992 Aug;28(1):15-9

The present study reports on a new model employing papaya latex as an inflammagen for testing anti-inflammatory activity. The activity of chloroquine, levamisole, and boswellic acids was significantly more against the papaya latex inflammation model than the carrageenan-induced inflammation model. The inflammation caused by latex may be attributed to both of its hydrolytic enzymes papain and chymopapain. The papaya latex inflammation animal model may prove useful for discovering novel and effective anti-rheumatoid arthritis drugs.


Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase

Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, Ammon HP J Pharmacol Exp Ther. 1992 Jun;261(3):1143-6

The study focused on isomers (α- and β-) of boswellic acids (BAs), 11-keto-β-BA and their acetyl derivatives isolated from Boswellia serrata. Among the BAs, acetyl-11-keto-β-BA induced inhibition of 5-lipoxygenase (5-LO) product formation with an IC50 of 1.5 microM. BAs showed concentration-dependent inhibitory action on 5-LO but lack did not affect cycloxygenase, 12-lipoxygenase, and peroxidation of arachidonic acid. Together, data strongly suggest that BAs are specific, non-reducing type inhibitors of the 5-LO either by direct interaction with 5-LO or by blocking its translocation.


Protection by boswellic acids against galactosamine/endotoxin-induced hepatitis in mice

Safayhi H, Mack T, Ammon HP Biochem Pharmacol. 1991 May 15;41(10):1536-7