Research Highlights
1990 - 1997
on Boswellin 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); 460-463
The present study focused on the frankincense extracts for anti inflammatory effects. While screening for additional effects of boswellic acids they observed that acetyl-11-keto-beta-boswellic acid a direct, non-redox and non-competitive 5 lipooxygenase inhibitor and decreased activity of elastase HLE. The data show the dual inhibition of 5-lipoxygenase and HLE is unique to boswellic acids. The blockade of two proinflammatory enzymes might be the rationale for putative antiphlogistic activity of acetyl-11-keto-beta-boswellic acid.

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

Here in this paper authors investigated on the treatment options for ulcerative colitis. Colitis is a chronic inflammatory disease of colon where leukotrienes play a key role in inflammation. Boswellic acids have been shown to be specific, non-redox, non-competitive inhibitors of 5-lipoxygenase. In grade II and III colitis patients the positive effect of Boswellia serrata was observed.

Böker, D-K and Winking, M. (1997), Dtsch. Ärzteblatt 94, 1197
Majeed, M., Badmaev, V., Gopinathan, S., Rajendran, R., Norton, T., and Braly, J. (1996)
Boswellin® The Anti-inflammatory Phytonutrient Nutriscience Publishers Inc., Piscataway, NJ

Acetyl-11-keto-beta-boswellic acid (AKBA): 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); 615-618
In this study investigators researched into the effect of natural pentacyclic triterpenes and their derivatives on 5-LOX activity. The results demonstrate that pentacyclic triterpene ring is crucial for binding to highly selective effector site, whereas functional groups are essential for 5-LOX inhibitory activity.

CPT-11 in the treatment of colorectal cancer: Clinical efficacy and safety profile.
Rougier, P. and Bugat, R.
Semin Oncol. 1996 23, 34-41.

In this paper authors reviewed on the data obtained on a new promising compound named CPT-11 (irinotecan) which can be used as an anticancer agent. The clinical utility of CPT-11 in advanced colorectal cancer has been documented in more than 400 patients recruited in phase II clinical trials in Europe, Japan and United States. Thirty-two percent of the patients had no evidence of disease progression at 6 months. The principal adverse events of CPT-11 are neutropenia and delayed diarrhea. In conclusion, CPT-11 has shown promising antitumor activity in the treatment of patients with advanced colorectal cancer, including those refractory to 5-fluoro uracil (5-FU)-based regimens, suggesting no cross-resistance to 5-FU.

Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid
Safayhi H, Sailer ER, Ammon HP
Mol Pharmacol 1995 Jun; 47(6); 1212-1216

This study reports on the mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid. The inhibition by acetyl-11-keto-beta-boswellic acid were not due to non-specific lipophilic interactions, because lipophilic four-ring compounds neither inhibited the activity of the 5-lipoxygenase nor antagonized the inhibitory action of acetyl-11-keto-beta-boswellic acid. They conclude that acetyl-11 keto-beta-boswellic acid acts directly on the 5-lipoxygenase enzyme.

Selective inhibitors of 5-lipoxygenase reduce CML blast cell proliferation and induce limited differentiation and apoptosis
Anderson, K.M., Seed, T., Plate, J.M., Jajeh, A., Meng, J., and Harris, J.E
Leukotrine Res. 1995 95, 789-801

Authors in this report focused on the inhibitors of arachidonic acid metabolizing enzyme, 5-lipoxygenase that reduce the rate of proliferation of chronic myelo genous leukemia [CML] blast cells. The inhibitory agents studied were ETYA, A63162 and SC41661A. These reagents induced differentiation of cultured CML cells. U937 cells cultured with ETYA, A63162 or SC41661A for 48 h exhibited apoptosis. MK886, an inhibitor of 5-lipoxygenase with a mechanism of action distinct from oxidation/reduction also inhibited CML and U937 cell proliferation and induced apoptosis.

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); 95-98

In this paper authors used papaya latex-induced rat paw inflammation model for evaluating anti-inflammatory activity. Drugs such as; aspirin, indomethacin, piroxicam, ibuprofen, prednisolone, levamisole, chloroquine, Boswellic acids showed antiinflammatory activity. Present study was undertaken to study in detail the sensitivity of this model for clinically effective, anti arthritic drugs. Thus the slowly acting antiarthritic drugs will be identified as those displaying significant activity in the papaya latex model.

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); 61-69

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

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 focused on the anticancer drugs originating from plants in China. Indirubin from Indigofera tinctoria is useful for the treatment of chronic myelocytic leukemia. Irisquinone from Iris latea pallasii and 10-hydroxy camptothecin from Camptotheca accuminata have exhibited definite activity on rodent tumors. The search for new anticancer drugs will be a fruitful frontier in cancer treatment and chemoprevention.

The role of leukotrienes in inflammation
Henderson, W.R
Ann. Intern. Med 1994 121; 684-697

This report reviews the biochemistry and biological activities of leukotrienes, focusing on their role in the inflammatory diseases such as asthma, psoriasis, arthritis and ulcerative colitis. He summarises the data on drugs that block the receptor mediated actions of leukotrienes. Leukotrienes are biologically active 5-lipoxygenase products of arachidonic acid metabolism that are involved in the mediation of various inflammatory disorders. Of these, leukotriene B4, sulfide peptide leukotrienes C4, D4 and E4 exert their biological actions through ligand-receptor interactions. Thus selective leukotriene inhibitors and receptor antagonists will probably become important group of anti-inflammatory drugs.

Mechanism of antiinflammatory actions of curcumine and boswellic acids
Ammon HP, Safayhi H, Mack T, Sabieraj J
J Ethnopharmacol 1993 Mar; 38(2-3); 113-119

Authors in this report explored on the combination effect of Curcumine from Curcuma longa and the gum resin of Boswellia serrata and explored their beneficial effects. Curcumine inhibited 5-lipoxygenase activity, 12-lipoxygenase and cyclooxygenase activity in human platelets. Boswellic acids inhibited leukotriene synthesis via 5-lipoxygenase, but did not affect the 12-lipoxygenase and cyclooxygenase activities. The data suggest that effect of boswellic acids are specific, non-redox inhibitors of leukotriene synthesis.

Ford Hutchinson AW, Gresser M, and Young, RN
Ann. Rev. Biochem. 1993 63; 383-417

Programmed cell death and the control of cell survival: Lessons from the nervous system
Raff, M.C., Barres, B.A., Burne, J.F., Coles, H.S., Ishizaki, Y., and Jacobson, M.D
Science 1993 262; 695-700

Authors reviewed on the mechanism by which many types of neurons die soon after they form synaptic connections with their target cells. This massive cell death is thought to reflect on the failure of neurons to obtain adequate amounts of specific neurotrophic factors required for their survival. These survival signals seem to act by suppressing an intrinsic cell suicide program.

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); 1139-1143

In this study the authors focused on Boswellic acids (BA), an anti-inflammatory, anti-arthritic agent and found BA to possess anticomplementary activity. Higher concentrations of BA showed constant inhibitory effects on immuno haemolysis. BA also exhibited weak inhibitory effects on individual components of the complement system.

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); 15-19

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 latex as compared to carrageenan model. The inflammation caused by latex may be attributed to both its hydrolytic enzymes papain and chymopapain. The papaya latex model may prove useful for developing effective 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); 1143-1146

Authors in this study focused on Isomers (alpha- and beta-) of boswellic acids (BAs), 11-keto-beta-BA and their acetyl derivatives were isolated from Boswellia serrata. Among the BAs, acetyl-11-keto-beta-BA induced inhibition of 5-lipoxygenase (5-LO) product formation with an IC50 of 1.5 microM. The data strongly suggest that BAs are specific, nonreducing type inhibitors of the 5-LO product formation either interacting directly with the 5-LO or blocking its translocation.

Development of 2,3-dihydro-6-(3-phenoxypropyl)-2-(2-phenylethyl)-5 benzofuranol (L-670,630) as a potent and orally active inhibitor of 5 lipoxygenase
Lau, C.K., Belanger, P.C., Dufresne C., Scheigetz, J., Therien, M., Fitzsimmons, B., Young, R.N., Ford-Hutchinson, A.W., Riendeau, D., Denis, D., Guay, J., Charleson, S., Piechuta, H., McFarlane, C.S., Chiu, S.H.L., Eline, D., Alvaro, R.F., Miwa, G., and Walsh, J.L
J. Med. Chem. 1992 35; 1299-1318

The present study explored on the role of leukotrienes as potent biological mediators of inflammatory disease. They investigated on the synthesis and biological activity of the three series of 2, 3-di hydro-2, 6-disubstituted-5-benzofuranols. Compounds were evaluated for their ability to inhibit the production of leukotriene B4 in human peripheral blood polymorphonuclear leukocytes and result in 5-lipoxygenase inhibition. The series 2, 3-dihydro-6-(3-phenoxy propyl)-2-(2-phenylethyl)-5-benzofuranol was chosen for development.

New phytotherapeutic agent for treatment of arthritis and allied disorders with novel mode of action
Singh, G.B. et al
IV and Int. Congress on Phytotherapy, Munich, Germany, 1992 Abstract SL 74

Protection by boswellic acids against galactosamine/endotoxin-induced hepatitis in mice
Safayhi H, Mack T, Ammon HP
Biochem Pharmacol 1991 May 15; 41(10); 1536-1537

Mechanisms and functions of cell death
Ellis, R.E., Yuan, J.Y., and Horvitz, H.R
Ann. Rev. Cell. Biol. 1991 7, 663-698

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