Boswellia serrata

An Overall Assessment of In Vitro, Preclinical, Pharmacokinetic and Clinical Data

Abstract

Non-steroidal anti-inflammatory drug (NSAID) intake is associated with high prevalence of gastrointestinal or cardiovascular adverse effects. All efforts to develop NSAIDs that spare the gastrointestinal tract and the cardiovasculature are still far from achieving a breakthrough. In the last two decades, preparations of the gum resin of Boswellia serrata (a traditional ayurvedic medicine) and of other Boswellia species have experienced increasing popularity in Western countries. Animal studies and pilot clinical trials support the potential of B. serrata gum resin extract (BSE) for the treatment of a variety of inflammatory diseases like inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and asthma. Moreover, in 2002 the European Medicines Agency classified BSE as an ‘orphan drug’ for the treatment of peritumoral brain oedema. Compared to NSAIDs, it is expected that the administration of BSE is associated with better tolerability, which needs to be confirmed in further clinical trials.

Until recently, the pharmacological effects of BSE were mainly attributed to suppression of leukotriene formation via inhibition of 5-lipoxygenase (5-LO) by two boswellic acids, 11-keto-β-boswellic acid (KBA) and acetyl-11-keto-β-boswellic acid (AKBA). These two boswellic acids have also been chosen in the monograph of Indian frankincense in European Pharmacopoiea 6.0 as markers to ensure the quality of the air-dried gum resin exudate of B. serrata. Furthermore, several dietary supplements advertise the enriched content of KBA and AKBA. However, boswellic acids failed to inhibit leukotriene formation in human whole blood, and pharmacokinetic data revealed very low concentrations of AKBA and KBA in plasma, being far below the effective concentrations for bioactivity in vitro. Moreover, permeability studies suggest poor absorption of AKBA following oral administration. In view of these results, the previously assumed mode of action — that is, 5-LO inhibition — is questionable. On the other hand, 100-fold higher plasma concentrations have been determined for β-boswellic acid, which inhibits microsomal prostaglandin E synthase-1 and the serine protease cathepsin G. Thus, these two enzymes might be reasonable molecular targets related to the anti-inflammatory properties of BSE. In view of the results of clinical trials and the experimental data from in vitro studies of BSE, and the available pharmacokinetic and metabolic data on boswellic acids, this review presents different perspectives and gives a differentiated insight into the possible mechanisms of action of BSE in humans. It underlines BSE as a promising alternative to NSAIDs, which warrants investigation in further pharmacological studies and clinical trials.

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References

  1. 1.

    Jones R, Rubin G, Berenbaum F, et al. Gastrointestinal and cardiovascular risks of nonsteroidal anti-inflammatory drugs. Am J Med 2008; 121: 464–74

    PubMed  CAS  Article  Google Scholar 

  2. 2.

    Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med 1998; 105: 31S–8S

    PubMed  CAS  Article  Google Scholar 

  3. 3.

    Delco F, Michetti P, Beglinger C, et al. Health care resource utilization and costs of NSAID-induced gastrointestinal toxicity: a population based study in Switzerland. Digestion 2004; 69: 10–9

    PubMed  Article  Google Scholar 

  4. 4.

    Silverstein F, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. The CLASS Study: a randomized controlled trial. JAMA 2000; 284: 1247–55

    PubMed  CAS  Article  Google Scholar 

  5. 5.

    Farooq M, Haq I, Qureshi AS. Cardiovascular risks of COX inhibition: current perspectives. Expert Opin Pharmacother 2008; 9: 1311–9

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case control study. Lancet 2005; 365: 475–81

    PubMed  CAS  Google Scholar 

  7. 7.

    Abdel-Tawab M, Zettl H, Schubert-Zsilavecz M. Nonsteroidal anti-inflammatory drugs: a critical review on current concepts applied to reduce gastrointestinal toxicity. Curr Med Chem 2009; 16(16): 2042–63

    PubMed  CAS  Article  Google Scholar 

  8. 8.

    Poeckel D, Werz O. Boswellic acids: biological actions and molecular targets. Curr Med Chem 2006; 13: 3359–69

    PubMed  CAS  Article  Google Scholar 

  9. 9.

    Winking M, Sarikaya S, Rahmanian A, et al. Boswellic acids inhibit glioma growth: a new treatment option?. J Neurooncol 2000; 46(2): 97–103

    PubMed  CAS  Article  Google Scholar 

  10. 10.

    Basch E, Boon H, Davies-Heerema T, et al. Boswellia: an evidence-based systematic review by the natural standard research collaboration. J Herb Pharmacother 2004; 4(3): 63–83

    Article  Google Scholar 

  11. 11.

    Safayhi H, Mack T, Sabieraj J, et al. Boswellic acids: novel, specific nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther 1992; 261: 1143–6

    PubMed  CAS  Google Scholar 

  12. 12.

    Siemoneit U, Pergola C, Jazzar B, et al. On the interference of boswellic acids with 5-lipoxygenase: mechanistic studies in vitro and pharmacological relevance. Eur J Pharmacol 2009; 606(1-3): 246–54

    PubMed  CAS  Article  Google Scholar 

  13. 13.

    Buechele B, Simmet T. Analysis of 12 different petnacyclic triterpneic acids from frankincense in human plasma by high performance liquid chromatography and photdiode array detection. J Chromatogr B 2003; 795: 355–62

    Article  CAS  Google Scholar 

  14. 14.

    Kreck C, Saller R. Indischer Weihrauch und seine Zubereitungen einschließlich H15 als traditionelles und modernes Therapeutikum. Internist Prax 1998; 38: 857–72

    Google Scholar 

  15. 15.

    Ennet D, Poetsch F, Gröditsch D. Indischer Weihrauch. Dtsch Apoth Ztg 2000; 140: 105–13

    Google Scholar 

  16. 16.

    Gupta I, Parihar A, Malhotra P, et al. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res 1997; 2(1): 37–43

    PubMed  CAS  Google Scholar 

  17. 17.

    Krieglstein CF, Anthoni C, Rijcken EJM, et al. Acetyl-11-keto-β-boswellic acid, a constituent of herbal medicine from Boswellia serrata resin, attenuates experimental ileitis. Int J Colorectal Dis 2001; 16: 88–95

    PubMed  CAS  Article  Google Scholar 

  18. 18.

    Sterk V, Buechele B, Simmet T. Effect of food intake on the bioavailability of boswellic acids from herbal preparation in healthy volunteers. Planta Med 2004; 70: 1155–60

    PubMed  CAS  Article  Google Scholar 

  19. 19.

    Gupta I, Gupta V, Parihar A, et al. Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Eur J Med Res 1998; 3(11): 511–4

    PubMed  CAS  Google Scholar 

  20. 20.

    Ganzera M, Khan IA. A reversed high performance liquid chromatography method for the analysis of boswellic acids in Boswellia serrata. Planta Med 2001; 67: 778–80

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    Tawab MA, Kaunzinger A, Bahr U, et al. Development of a high-performance liquid chromatographic method for the determination of 11-keto-beta-boswellic acid in human plasma. J Chromatogr B Biomed Sci 2001; 761(2): 221–7

    CAS  Article  Google Scholar 

  22. 22.

    Sharma S, Thawani V, Hingorani L, et al. Pharmacokinetic study of 11-keto-β-boswellic acid. Phytomedicine 2004; 11: 255–60

    PubMed  CAS  Article  Google Scholar 

  23. 23.

    Tausch L, Henkel A, Siemoneit U, et al. Identification of human cathepsin G as a functional target of boswellic acids from the anti-inflammatory remedy frankincense. J Immunol 2009; 183: 3433–42

    PubMed  CAS  Article  Google Scholar 

  24. 24.

    Ammon HPT. Boswellic acids in chronic inflammatory diseases. Planta Med 2006; 72(12): 1100–16

    PubMed  CAS  Article  Google Scholar 

  25. 25.

    Krüger P, Daneshfar R, Eckert GP, et al. Metabolism of boswellic acids in vitro and in vivo. Drug Metab Dispos 2008; 36(6): 1135–42

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Reising K, Meins J, Bastian B, et al. Determination of boswellic acids in brain and plasma by high-performance liquid chromatography/tandem mass spectrometry. Anal Chem 2005; 77(20): 6640–5

    PubMed  CAS  Article  Google Scholar 

  27. 27.

    Krüger P, Kanzer J, Hummel J, et al. Permeation of Boswellia extract in the Caco-2 model and possible interactions of its constituents KBA and AKBA with OATP1B3 and MRP2. Eur J Pharm Sci 2009; 36(2-3): 275–84

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Gerhardt H, Seifert F, Buvari P, et al. Therapie des aktiven Morbus Crohn mit Boswellia serrata Extrakt H15. Z Gastroenterol 2001; 39: 11–7

    PubMed  CAS  Article  Google Scholar 

  29. 29.

    Gupta I, Parihar A, Malhotra P, et al. Effects of gum resin of Boswellia serrata on patients with chronic colitis. Planta Med 2001; 67(5): 391–5

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Madisch A, Miehlke S, Eichele O, et al. Boswellia serrata extract for the treatment of collagenous colitis: a double-blind, randomized, placebo-controlled, multicenter trial. Int J Colorectal Dis 2007; 22: 1445–51

    PubMed  Article  Google Scholar 

  31. 31.

    Anthoni C, Laukoetter MG, Rijcken E, et al. Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis. Am J Physiol Gastrointest Liver Physiol 2006; 290: G1131–7

    PubMed  CAS  Article  Google Scholar 

  32. 32.

    Kiela PR, Midura AJ, Kuscuoglu N, et al. Effects of Boswellia serrata in mouse models of chemically induced colitis. Am J Physiol Gastrointest Liver Physiol 2005; 288: G798–808

    PubMed  CAS  Article  Google Scholar 

  33. 33.

    Yamada T, Deitch E, Specian RD, et al. Mechanisms of acute and chronic intestinal inflammation induced by indomethacin. Inflammation 1993; 17: 641–62

    PubMed  CAS  Article  Google Scholar 

  34. 34.

    Syrovets T, Büchele B, Krauss C, et al. Acetyl-boswellic acids inhibit lipo-polysaccharide-mediated TNF-α induction in monocytes by direct interaction with IκB kinases. J Immunol 2005; 174: 498–506

    PubMed  CAS  Google Scholar 

  35. 35.

    Roy S, Khanna S, Shah H, et al. Human genome screen to identify the genetic basis of the anti-inflammatory effects of Boswellia in microvascula en-dothelial cells. DNA Cell Biol 2005; 24: 244–55

    PubMed  CAS  Article  Google Scholar 

  36. 36.

    Chevrier MR, Ryan AE, Lee DY, et al. Boswellia carterii extract inhibits Th1 cytokines and promotes Th2 cytokines in vitro. Clin Diagn Lab Immunol 2005; 12: 575–80

    PubMed  CAS  Google Scholar 

  37. 37.

    Moussaieff A, Shein NA, Tsenter J, et al. Incensole acetate: a novel neuro-protective agent isolated from Boswellia carterii. J Cereb Blood Flow Metab 2008; 28:1341–52

    PubMed  CAS  Article  Google Scholar 

  38. 38.

    Khajuria A, Gupta A, Suden P, et al. Imunomodulatory activity of biopo-lymeric fraction BOS 2000 from Boswellia serrata. Phytother Res 2008; 22(3): 340–8

    PubMed  CAS  Article  Google Scholar 

  39. 39.

    Khajuria A, Gupta A, Malik F, et al. A new vaccine adjuvant (BOS 2000) a potent enhancer mixed Th1/Th2 immune responses in mice immunized with HbsAg. Vaccine 2007; 25(23): 4586–94

    PubMed  CAS  Article  Google Scholar 

  40. 40.

    Harizi H, Corcuff J-B, Gualde N. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol Med 2008; 14(10): 461–9

    PubMed  CAS  Article  Google Scholar 

  41. 41.

    Ammon HP, Mack T, Singh GB, et al. Inhibition of leukotriene B4 formation in rat peritoneal neutrophils by an ethanolic extract of the gum resin exudate of Boswellia serrata. Planta Med 1991; 57: 203–7

    PubMed  CAS  Article  Google Scholar 

  42. 42.

    Sailer ER, Schweizer S, Boden SE, et al. Acetyl-11-keto-beta-boswelic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity. Brit J Pharmacol 1996; 117: 615–8

    CAS  Article  Google Scholar 

  43. 43.

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

    PubMed  CAS  Google Scholar 

  44. 44.

    Werz O, Schneider N, Brungs M, et al. A test system for leukotriene synthesis inhibitors based on the in-vitro differentiation of the human leukemic cell lines HL-60 and Mono Mac 6. Naunyn Schmied Arch Pharmacol 1997; 356(4): 441–5

    CAS  Article  Google Scholar 

  45. 45.

    Werz O, Szellas D, Henseler M, et al. Nonredox 5-lipoxygenase inhibitors require glutathione peroxidase for efficient inhibition of 5-lipoxygenase activity. Mol Pharmacol 1998; 54: 445–50

    PubMed  CAS  Google Scholar 

  46. 46.

    Werz O, Steinhilber D. Therapeutic options for 5-lipoxygenase inhibitors. Pharmacol Ther 2006; 112(3): 701–8

    PubMed  CAS  Article  Google Scholar 

  47. 47.

    Altmann A, Fischer L, Schubert-Zsilavecz M, et al. Boswellic acids activate p42 (MAPK) and p38 (MAPK) and stimulate Ca (2+) mobilization. Biochem Biophy Res Commun 2002; 290: 185–90

    CAS  Article  Google Scholar 

  48. 48.

    Altmann A, Poeckel D, Fischer L, et al. Coupling of boswellic acid-induced Ca2+ mobilisation and MAPK activation of lipid metabolism and peroxide formation in human leucocytes. Br J Pharmacol 2004; 141: 223–32

    PubMed  CAS  Article  Google Scholar 

  49. 49.

    Safayhi H, Boden SE, Schweizer S, et al. Concentration-dependent potentiating and inhibitory effects of Boswellia extracts on 5-lipoxygenase product formation in stimulated PMNL. Planta Med 2000; 66: 110–3

    PubMed  CAS  Article  Google Scholar 

  50. 50.

    Poeckel D, Tausch L, Kather N, et al. Boswellic acids stimulate arachidonic acid release and 12-lipoxygenase activity in human platelets independent of Ca2+ and differentially interact with platelet-type 12-lipoxygenase. Mol Pharmacol 2006; 70: 1071–8

    PubMed  CAS  Article  Google Scholar 

  51. 51.

    Boden SE, Schweizer S, Bertsche T, et al. Stimulation of leukotriene synthesis in intact polymorphnuclear cells by the 5-lipoxygenase 3-oxotirucallic acid. Mol Pharmacol 2001; 60: 267–73

    PubMed  CAS  Google Scholar 

  52. 52.

    Kim JH, Tagari P, Griffiths AM, et al. Levels of peptidoleukotrienes E4 are elevated in active Crohn’s disease. J Pediatr Gastroenterol Nutr 1995; 20:403–7

    PubMed  CAS  Article  Google Scholar 

  53. 53.

    Ikehata A, Hiwatashi N, Kinouchi Y, et al. Altered leukotriene B4 metabolism in colonic mucosa with inflammatory bowel disease. Scand J Gastroenterol 1995; 30: 44–9

    PubMed  CAS  Article  Google Scholar 

  54. 54.

    Murthy S, Murthy NS, Coppola D, et al. The efficacy of BAY y 1015 in dextran sulphate model of mouse colitis. Inflamm Res 1997; 46: 224–33

    PubMed  CAS  Article  Google Scholar 

  55. 55.

    Zingarelli B, Squadrito F, Graziani P, et al. Effects of zileuton, a new 5-lipoxygenase inhibitor, in experimentally induced colitis in rats. Agents Actions 1993; 39: 150–6

    PubMed  CAS  Article  Google Scholar 

  56. 56.

    Laursen LS, Naesdal J, Bukhave K, et al. Selective 5-lipoxygenase inhibition in ulcerative colitis. Lancet 1990; 335: 683–5

    PubMed  CAS  Article  Google Scholar 

  57. 57.

    Hillingso J, Kjeldsen J, Laursen LS, et al. Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis. Clin Pharmacol Ther 1995; 57: 335–41

    PubMed  CAS  Article  Google Scholar 

  58. 58.

    Zaher H, Khan AA, Palandra J, et al. Breast cancer resistance protein (Bcrp/abcg2) is a major determinant of sulfasalzine absorption and elimination in mouse. Mol Pharm 2006; 3(1): 55–61

    PubMed  CAS  Article  Google Scholar 

  59. 59.

    Steinhilber D. 5-Lipoxygenase: a target for antiinflammatory drugs revisited. Curr Med Chem 1999; 6: 71–85

    PubMed  CAS  Google Scholar 

  60. 60.

    Christman JW, Lancaster LH, Blackwell TS. Nuclear factor NFκB: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med 1998; 24: 1131–8

    PubMed  CAS  Article  Google Scholar 

  61. 61.

    Schreiber S, Nikolaus S, Hampe J. Activation of nuclear factor KB in inflammatory bowel disease. Gut 1998; 42: 477–84

    PubMed  CAS  Article  Google Scholar 

  62. 62.

    Gan H-T, Chen Y-Q, Ouyang Q. Sulfasalzine inhibits activation of nuclear factor-kB in patients with ulcerative colitis. J Gastroenterol Hepat 2005; 20: 1016–24

    CAS  Article  Google Scholar 

  63. 63.

    Rijcken E, KriegeIstein CF, Anthoni C, et al. ICAM-1 and VCAM-1 anti-sense oligonucleotides attenuate in vivo leucocyte adherence and inflammation in rat inflammatory bowel disease. Gut 2002; 51: 529–35

    PubMed  CAS  Article  Google Scholar 

  64. 64.

    Hammato N, Meamura K, Hirate M, et al. Inhibition of dextran sulphate sodium (DSS)-induced colitis in mice by intracolonically administered antibodies against adhesion molecules (endothelial leucocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1)). Clin Exp Immunol 1999; 117: 462–8

    Article  Google Scholar 

  65. 65.

    van Deventer SJ, Tami JA, Wedel MK. A randomised controlled double blind, escalating dose study of alicaforsen enema in active ulcerative colitis. Gut 2004; 53: 1646–51

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Ramakers JD, Mensink RP, Schaart G, et al. Arachidnoic acid but not eicosapentaenoic acid (EPA) and oleic acid activates NF-KB and elevates ICAM-1 expression in Caco-2 cells. Lipids 2007; 42: 687–98

    PubMed  CAS  Article  Google Scholar 

  67. 67.

    Saklatavala J. Glucocorticoids: do we know how they work?. Arthritis Res 2002; 4: 146–50

    Article  Google Scholar 

  68. 68.

    Dabek M, Ferrier L, Roka R, et al. Luminal cathepsin G and protease-acti-vated receptor 4: a duet involved in alterations of the colonic epithelial barrier in ulcerative colitis. Am J Pathol 2009; 175(1): 207–14

    PubMed  CAS  Article  Google Scholar 

  69. 69.

    Kuwana T, Saot Y, Saka M, et al. Anti-cathepsin G antibodies in the sera of patients with ulcerative colitis. J Gastroenterol 2000; 35(9): 682–9

    PubMed  CAS  Article  Google Scholar 

  70. 70.

    Ooi CJ, Lim BL, Cheong WK, et al. Antineutrophil cytoplasmic antibodies (ANCAs) in patients with inflammatory bowel disease show no correlation with proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G and lysozyme: a Singapore study. Ann Acad Med Singapore 2000; 29(6): 704–7

    PubMed  CAS  Google Scholar 

  71. 71.

    Sander O, Herborn G, Rau R. Is H15 (resin extract of Boswellia serrata, “incense”) a useful supplement to established drug therapy of chronic polyarthritis? Results of a double-blind pilot study. Z Rheumatol 1998; 57(1): 11–6

    PubMed  CAS  Article  Google Scholar 

  72. 72.

    Kimmatkar N, Thawani V, Hingorani L, et al. Efficacy and tolerability of Boswellia serrata extract in the treatment of osteoarthritis of knee: a randomized double blind placebo controlled trial. Phytomedicine 2003; 10: 3–7

    PubMed  CAS  Article  Google Scholar 

  73. 73.

    Sontakke S, Thawani V, Pimpalkhute P, et al. Open, randomized, controlled clinical trial of Boswellia serrata extract as compared to valdecoxib in osteoarthritis of knee. Indian J Pharmacol 2007; 39: 27–9

    Article  Google Scholar 

  74. 74.

    Sengupta K, Alluri KV, Satish AR, et al. A double-blind, randomized, placebo-controlled study of the efficacy and safety of 5-Loxin® for treatment of osteoarthritis of the knee. Arthritis Res Ther 2008; 10(4): R85

    PubMed  Article  CAS  Google Scholar 

  75. 75.

    Etzel R. Special extract of Boswellia serrata (H15) in the treatment of rheumatoid arthritis. Phytomed 1996; 3: 91–4

    CAS  Article  Google Scholar 

  76. 76.

    Chopra A, Lavin P, Patwardhan B, et al. Randomized double blind trial of an ayurvedic plant derived formulation for the treatment of rheumatoid arthritis. J Rheumatol 2000; 27(6): 1365–72

    PubMed  CAS  Google Scholar 

  77. 77.

    Kulkarni RR, Patki PS, Jog VP, et al. Efficacy of an ayurvedic formulation in rheumatoid arthritis: a double-blind, placebo-controlled, cross-over study. Indian J Pharm 1992; 24: 98–101

    Google Scholar 

  78. 78.

    Singh GB, Singh S, Bani S. Anti-inflammatory actions of boswellic acids. Phytomed 1996; 3(1): 81–5

    CAS  Article  Google Scholar 

  79. 79.

    Singh GB, Atal CK. Pharmacology of an extract of salai guggal ex-Boswellia serrata, a new non-steroidal anti-inflammatory agent. Agents Actions 1986; 18:407–12

    PubMed  CAS  Article  Google Scholar 

  80. 80.

    Fan AY, Lao L, Zhang RX, et al. Effects of an acetone extract of Boswellia carterii Birdw.(Burseraceae) gum resin on rats with persistent inflammation. J Altern Complement Med 2005; 11: 323–31

    PubMed  Article  Google Scholar 

  81. 81.

    Fan AY, Lao L, Zhang RX, et al. Effects of an acetone extract of Boswellia carterii Birdw.(Burseraceae) gum resin on adjuvant-induced arthritis in Lewis rats. J Ethnopharmacol 2005; 101(1-3): 104–9

    PubMed  CAS  Article  Google Scholar 

  82. 82.

    Gupta OO, Sharma N, Chand D. A sensitive and relevant model for evaluating anti-inflammatory activity-papaya latex-induced rat paw inflammation. J Pharmacol Toxicol Meth 1992; 28(1): 15–9

    CAS  Article  Google Scholar 

  83. 83.

    Gupta OO, Sharma N, Chand D. Application of papaya latex-induced rat paw inflammation: model for evaluation of slowly acting antiarthritic drugs. J Pharmacol Toxicol Meth 1994; 31(2): 95–8

    CAS  Article  Google Scholar 

  84. 84.

    Banno N, Akihisa T, Yasukawa K, et al. Anti-inflammatory activities of the triterpene acids from the resin of Boswellia carteri. J Ethnopharmacol 2006; 107(2): 249–53

    PubMed  CAS  Article  Google Scholar 

  85. 85.

    Sharma ML, Khajuria A, Kaul A, et al. Effect of salai guggal ex-Boswellia serrata on cellular and hunoral immune responses and leukocate migration. Agents Action 1988; 24: 161–4

    CAS  Article  Google Scholar 

  86. 86.

    Sharma ML, Bani S, Singh GB. Anti-arthritic activity of boswellic acids in bovine serum albumin (BSA)-induced arthritis. Int J Immunopharmacol 1989; 11(6): 647–52

    PubMed  CAS  Article  Google Scholar 

  87. 87.

    Wildfeuer A, Neu IS, Safayhi H, et al. Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis. Arzneimittelforschung 1998; 48: 668–74

    PubMed  CAS  Google Scholar 

  88. 88.

    Reichling J, Schmökel H, Fitzi J, et al. Dietary support with Boswellia resin in canine inflammatory joint and spinal disease. Schweiz Arch Tierheilkd 2004; 146: 71–9

    PubMed  CAS  Article  Google Scholar 

  89. 89.

    Duwieja M, Zeitlin IJ, Waterman PG, et al. Anti-inflammatory activity of resins from some species of the plant family Burseraceae. Planta Med 1993; 59: 12–6

    Article  Google Scholar 

  90. 90.

    Siemoneit U, Hofmann B, Kather N, et al. Identification and functional analysis of cyclooxygenase-1 as a molecular target of boswellic acids. Bio-chem Pharmacol 2008; 75: 503–13

    CAS  Article  Google Scholar 

  91. 91.

    Fleming I. Epoxyeicosatrienoic acids, cell signalling and angiogenesis. Prostaglandins Other Lipid Mediat 2007; 82: 60–7

    PubMed  CAS  Article  Google Scholar 

  92. 92.

    Frank A, Unger M. Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolizing cytochrome P450 enzymes using liquid chromatography mass-spectrometry after automated on-line extraction. J Chromatogr A 2006; 1112(1-2): 255–62

    PubMed  CAS  Article  Google Scholar 

  93. 93.

    Safayhi H, Rall B, Sailer ER, et al. Inhibition by boswellic acids of human leukocyte elastase. J Pharmacol Exp Ther 1997; 281: 460–3

    PubMed  CAS  Google Scholar 

  94. 94.

    Szekanecz Z, Koch AE. Macrophages and their products in rheumatoid arthritis. Curr Opin Rheumatol 2007; 19(3): 289–95

    PubMed  Article  Google Scholar 

  95. 95.

    Mijata J, Tani K, Sato K, et al. Cathepsin G: the significance in rheumatoid arthritis as a monocyte chemoattractant. Rheumatol Int 2007; 27(4): 375–82

    Article  CAS  Google Scholar 

  96. 96.

    Peters-Golden M, Henderson Jr WR. Leukotrienes. N Engl J Med 2007; 357(18): 1841–54

    PubMed  CAS  Article  Google Scholar 

  97. 97.

    Ammon HPT. Salai guggal — Boswellia serrata: from a herbal medicine to a non-redox inhibitor of leukotriene biosynthesis. Eur J Med Res 1996; 1: 369–70

    PubMed  CAS  Google Scholar 

  98. 98.

    Fahmi H. mPGES-1 as a novel target for arthritis. Curr Opin Rheumatol 2004; 16(5): 623–7

    PubMed  CAS  Article  Google Scholar 

  99. 99.

    Sampey AV, Monrad S, Crofford LJ. Microsomal prostaglandin E synthasel: the inducible synthase for prostaglandin E2. Arthritis Res Ther 2005; 7(3): 114–7

    PubMed  CAS  Article  Google Scholar 

  100. 100.

    Kojima F, Kato S, Kawai S. Prostaglandin E synthase in the pathophysiology of arthritis. Fundam Clin Pharmacol 2005; 19(3): 255–61

    PubMed  CAS  Article  Google Scholar 

  101. 101.

    Siemoneit U, Koeberle A, Rossi A, et al. Inhibition of micosomal prostaglandin E2 synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense. Br J Pharmacol 2011 Jan;162(1): 147–62

    PubMed  CAS  Article  Google Scholar 

  102. 102.

    Portonova JP, Zhang Y, Anderson GD, et al. Selective neutralization of prostaglandin E2 blocks inflammation, hyperalgesia, and interleukin 6 production in vivo. J Exp Med 1996; 184: 883–91

    Article  Google Scholar 

  103. 103.

    Pungle P, Banavalikar M, Suthar A, et al. Immunomodulatory activity of boswellic acids of Boswellia serrata Roxb. Indian J Exp Biol 2003; 41:1460–2

    PubMed  CAS  Google Scholar 

  104. 104.

    Wenzel SE. Arachidonic acid metabolites: mediators of inflammation in asthma. Pharmacother 1997; 17(1 Pt 2): 3S–12S

    CAS  Google Scholar 

  105. 105.

    Vancheri C, Mastruzzo C, Sortino MA, et al. The lung as a privileged site for the beneficial actions of PGE2. Trends Immunol 2004; 25(1): 40–6

    PubMed  CAS  Article  Google Scholar 

  106. 106.

    Böker DJ, Winking M. Die Rolle von Boswellia serrata in der Therapie maligner Gliome. Deutsches Ärzteblatt 1997; 94: B958–60

    Google Scholar 

  107. 107.

    Janssen G, Bude U, Breu H, et al. Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors. Klin Pädiatr 2000; 212: 189–95

    PubMed  CAS  Article  Google Scholar 

  108. 108.

    Streffer JR, Bitzer M, Schabet M, et al. Response of radiochemotherapy-associated cerebral edema to a phytotherapeutic agent, H15. Neurology 2001; 56(9): 1219–21

    PubMed  CAS  Article  Google Scholar 

  109. 109.

    Badie B, Schartner JM, Hagar AR, et al. Microglia cyclooxygenase-2 activity in experimental gliomas: possible role in cerebral edema formation. Clin Can Res 2003; 9: 872–7

    CAS  Google Scholar 

  110. 110.

    Ernst E. Frankincense: systematic review. BMJ 2008; 337: a2813

    PubMed  CAS  Article  Google Scholar 

  111. 111.

    Singh S, Khajuria A, Taneja SC, et al. The gastric ulcer protective effect of boswellic acids, a leukotriene inhibitor from Boswellia serrata, in rats. Phytomedicine 2008 Jun; 15(6-7): 408–15

    PubMed  CAS  Article  Google Scholar 

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Acknowledgements

No source of funding was used in the preparation of this review. The authors have no conflicts of interest that are relevant to the content of this review.

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Correspondence to Dr Mona Abdel-Tawab.

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Abdel-Tawab, M., Werz, O. & Schubert-Zsilavecz, M. Boswellia serrata. Clin Pharmacokinet 50, 349–369 (2011). https://doi.org/10.2165/11586800-000000000-00000

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Keywords

  • Inflammatory Bowel Disease
  • PGE2
  • Mesalazine
  • LTB4
  • Human Microvascular Endothelial Cell