Boswellia, Indian frankincense (Boswellia serrata)

Boswellia serrata is a tree prevalent in India, the Middle East, and North Africa. The gummy exudate or resin obtained by peeling away the bark is commonly known as frankincense or olibanum. The oldest written document mentioning boswellia as a drug is the papyrus Ebers written around 1500 BC.

Boswellia, Indian frankincense (Boswellia serrata)

Uses

Ayurvedic medicine uses different parts of the boswellia tree for the treatment of asthma, rheumatisms, dysentery, skin ailments, ulcers, blood purification, etc. It was also used as a perfume and in religious celebrations. The oil of boswellia is also known as Indian frankincense. The resin (a sticky substance found in trees and plants) is used to make an extract. Boswellia resin is used in Ayurvedic (traditional Indian) medicine. It is currently marketed as an anti-inflammatory supplement to support and improve joint health and mobility.

Chemistry/Pharmacology

The oleo gum-resins contain 30-60% resin, 5-10% essential oils, which are soluble in organic solvents, and the rest is made up of polysaccharides. Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. The resinous part of Boswellia serrata possesses monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids and four major pentacyclic triterpenic acids i.e. β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid, responsible for inhibition of pro-inflammatory enzymes. Out of these four boswellic acids, acetyl-11-keto-β-boswellic acid is the most potent inhibitor of 5-lipoxygenase, an enzyme responsible for inflammation.

The primary bioactive compound in boswellia is boswellic acid, a 5-lipoxygenase inhibitor with anti-inflammatory and anti-arthritic effects. It also demonstrated cytotoxic and radio-enhancing properties and prevented intestinal tumorigenesis in a murine model. Other animal studies suggest boswellia may improve cognitive impairment and insulin resistance. Essential oil of boswellia has also been shown to have antimicrobial activities.

Clinical Studies

In clinical studies, boswellic acid extracts, a formulation containing boswellia, Terminalia chebula and turmeric, as well as boswellic acid combined with curcumin were all reported useful in patients with osteoarthritis. In addition, a supplement containing boswellia and curcumin added to standard treatments alleviated symptoms of tendinopathy, and a formula containing black sesame extract oil, turmeric, and boswellia reduced acute musculoskeletal pain and was found comparable to acetaminophen. Boswellia may also benefit patients with bronchial asthma, ulcerative colitis, mild irritable bowel syndrome, and osteo-muscular pain.

Preliminary data suggest that boswellia may be effective in reducing cerebral edema in patients with brain tumors following radiotherapy; and in reducing radio-chemotherapy-induced cerebral edema in patients with primary glioblastoma multiforme. A boswellia-based cream was found useful in preventing skin damage due to radiotherapy in breast cancer patients; and a formulation of boswellic acid, betaine, and myo-inositol helped reduce mammary density, a risk factor for breast cancer. In addition, boswellia combined with propolis-derived polyphenols decreased genitourinary pain in men with prostatitis-like symptoms.

Biomechanical Mechanism

Boswellic acid, the major constituent of boswellia, is thought to contribute to most of the herb’s pharmacological activities. In vitro and animal studies show that anti-inflammatory activity occurs via inhibition of 5-lipoxygenase and cyclooxygenase-1. It also inhibits nuclear transcription factor KappaB (NF-KappaB) signaling, markedly decreasing the production of the key proinflammatory cytokine tumor necrosis factor (TNF-alpha). Unlike other non-steroidal anti-inflammatory drugs, however, boswellic acid failed to show analgesic or antipyretic effects.

Research on cytotoxic effects of boswellic acid indicates that it induces p21 expression through a p53-independent pathway and causes apoptosis in glioma and leukemia cell lines. A boswellia extract induced apoptosis in a cervical cancer cell line by inducing endoplasmic reticulum (ER) stress. Other apoptotic mechanisms include early generation of nitric oxide and reactive oxygen species that upregulated time-dependent expression of p53/p21/PUMA, inhibition of microsomal prostaglandin E synthase-1 (mPGES-1), and decreased prostaglandin (PGE2) levels and its downstream targets.

A semisynthetic analog of boswellic acid, 3-alpha-Butyryloxy-beta-boswellic acid, demonstrated significant growth inhibition in Ehrlich Ascitic Tumour (EAT), Ehrlich Ascitic Carcinoma (EAC) and Sarcoma-180 tumor models, via NF-KappaB downregulation and induction of poly (ADP-ribose) polymerase (PARP) cleavage. Acetyl-boswellic acids inhibited topoisomerases by competing with DNA for binding sites. Acetyl-11-keto-beta-boswellic acid (AKBA) inhibited human prostate tumor growth via inhibition of VEGFR2-induced angiogenesis. In vitro, antiplatelet effects of boswellia gum resin extracts are attributed to inhibition of clotting factors Xa and XIa.

Sources/Articles

Bannuru RR, Osani MC, Al-Eid F, Wang C. Efficacy of curcumin and Boswellia for knee osteoarthritis: Systematic review and meta-analysis. Semin Arthritis Rheum. 2018 Dec;48(3):416-429.

Belcaro G, Gizzi G, Pellegrini L, et al. Supplementation with a lecithin-based delivery form of Boswellia serrata extract (Casperome®) controls symptoms of mild irritable bowel syndrome. Eur Rev Med Pharmacol Sci. 2017 May;21(9):2249-2254.

Bhushan S, Malik F, Kumar A, et al. Activation of p53/p21/PUMA alliance and disruption of PI-3/Akt in multimodal targeting of apoptotic signaling cascades in cervical cancer cells by a pentacyclic triterpenediol from Boswellia serrata. Mol Carcinog. 2009 Dec;48(12):1093-108

Camarda L, Dayton T, Di Stefano V, Pitonzo R, Schillaci D. Chemical composition and antimicrobial activity of some oleogum resin essential oils from Boswellia spp. (Burseraceae). Ann Chim. 2007 Sep;97(9):837-44.

Chande N, MacDonald JK, McDonald JW. Interventions for treating microscopic colitis: a Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group systematic review of randomized trials. Am J Gastroenterol. 2009 Jan;104(1):235-41.

Conti S, Vexler A, Edry-Botzer L, et al. Combined acetyl-11-keto-beta-boswellic acid and radiation treatment inhibited glioblastoma tumor cells. PLoS One. 2018;13(7):e0198627.

Dahmen U, Gu YL, Dirsch O, et al. Boswellic acid, a potent antiinflammatory drug, inhibits rejection to the same extent as high dose steroids. Transplant Proc. Feb-Mar 2001;33(1-2):539-541.

Di Pierro F, Simonetti G, Petruzzi A, et al. A novel lecithin-based delivery form of Boswellic acids as complementary treatment of radiochemotherapy-induced cerebral edema in patients with glioblastoma multiforme: a longitudinal pilot experience. J Neurosurg Sci. 2019 Jun;63(3):286-291.

Franceschi F, Togni S, Belcaro G, et al. A novel lecithin based delivery form of Boswellic acids (Casperome®) for the management of osteo-muscular pain: a registry study in young rugby players. Eur Rev Med Pharmacol Sci. 2016 Oct;20(19):4156-4161

Frank MB, Yang Q, Osban J, et al. Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity. BMC Complement Altern Med. 2009 Mar 18;9:6.

Glaser T, Winter S, Groscurth P, et al. Boswellic acids and malignant glioma: induction of apoptosis but no modulation of drug sensitivity. Br J Cancer. May 1999;80(5-6):756-765.

Gomaa AA, Makboul RM, Al-Mokhtar MA, et al. Polyphenol-rich Boswellia serrata gum prevents cognitive impairment and insulin resistance of diabetic rats through inhibition of GSK3beta activity, oxidative stress and pro-inflammatory cytokines. Biomed Pharmacother. Jan 2019;109:281-292.

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. Nov 17 1998;3(11):511-514.

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

Haroyan A, Mukuchyan V, Mkrtchyan N, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018 Jan 9;18(1):7.

Henrotin Y, Dierckxsens Y, Delisse G, Seidel L, Albert A. Curcuminoids and Boswellia serrata extracts combination decreases tendinopathy symptoms: findings from an open-label post-observational study. Curr Med Res Opin. 2020 Dec 21:1-20.

Holtmeier W, Zeuzem S, PreiB, J, et al. Randomized, placebo-controlled, double-blind trial of Boswellia serrata in maintaining remission of Crohn’s disease. Inflamm Bowel Dis. 2011 Feb;17(2):573-82.

Jing Y, Nakajo S, Xia L, et al. Boswellic acid acetate induces differentiation and apoptosis in leukemia cell lines. Leuk Res. Jan 1999;23(1):43-50.

Kafil TS, Nguyen TM, Patton PH, et al. Interventions for treating collagenous colitis. Cochrane Database Syst Rev. Nov 11 2017;11:Cd003575.

Karlapudi V, Prasad Mungara AVV, Sengupta K, Davis BA, Raychaudhuri SP. A Placebo-Controlled Double-Blind Study Demonstrates the Clinical Efficacy of a Novel Herbal Formulation for Relieving Joint Discomfort in Human Subjects with Osteoarthritis of Knee. J Med Food. 2018 May;21(5):511-520.

Kim HR, Kim MS, Kwon DY, et al. Boswellia serrata-induced apoptosis is related with ER stress and calcium release. Genes Nutr. Feb 2008;2(4):371-374.

Kirste S, Treier M, Wehrle SJ, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: A prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer. 2011;117(16):3788-95.

Kokkiripati PK, Bhakshu LM, Marri S, et al. Gum resin of Boswellia serrata inhibited human monocytic (THP-1) cell activation and platelet aggregation. J Ethnopharmacol. 2011 Sep 1;137(1):893-901.

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. Dec 2007;22(12):1445-1451.

Mikhaeil BR, Maatooq GT, Badria FA, Amer MM. Chemistry and immunomodulatory activity of frankincense oil. Z Naturforsch C. 2003 Mar-Apr;58(3-4):230-8.

Pang X, Yi Z, Zhang X, et al. Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Cancer Res. 2009 Jul 15;69(14):5893-900.

Pasta V, Gullo G, Giuliani A, et al. An association of boswellia, betaine and myo-inositol (Eumastos(R)) in the treatment of mammographic breast density: a randomized, double-blind study. Eur Rev Med Pharmacol Sci. Nov 2015;19(22):4419-4426.

Qurishi Y, Hamid A, Sharma PR, et al. NF-κB down-regulation and PARP cleavage by novel 3-α-butyryloxy-β-boswellic acid results in cancer cell specific apoptosis and in vivo tumor regression. Anticancer Agents Med Chem. 2013 Jun;13(5):777-90.

Ranjbarnejad T, Saidijam M, Moradkhani S, Najafi R. Methanolic extract of Boswellia serrata exhibits anti-cancer activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells. Prostaglandins Other Lipid Mediat. 2017 May 24;131:1-8.

Rudrappa GH, Chakravarthi PT, Benny IR. Efficacy of high-dissolution turmeric-sesame formulation for pain relief in adult subjects with acute musculoskeletal pain compared to acetaminophen: A randomized controlled study. Medicine (Baltimore). 2020 Jul 10;99(28):e20373.

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. Mar 2000;66(2):110-113.

Safayhi H, Mack T, Sabieraj J, et al. Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther. Jun 1992;261(3):1143-1146.

Sibona M, Destefanis P, Agnello M, et al. The association of Boswellia resin extract and propolis derived polyphenols can improve quality of life in patients affected by prostatitis-like symptoms. Arch Ital Urol Androl. 2020 Jan 14;91(4):251-255.

Siemoneit U, Hofmann B, Kather N, et al. Identification and functional analysis of cyclooxygenase-1 as a molecular target of boswellic acids. Biochem Pharmacol. 2008 Jan 15;75(2):503-13.

Singh GB, Atal CK. Pharmacology of an extract of salai guggal ex-Boswellia serrata, a new non-steroidal anti-inflammatory agent. Agents Actions. Jun 1986;18(3-4):407-412.

Syrovets T, Buchele B, Gedig E, et al. Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and IIalpha. Mol Pharmacol. Jul 2000;58(1):71-81.

Togni S, Maramaldi G, Bonetta A, Giacomelli L, Di Pierro F. Clinical evaluation of safety and efficacy of Boswellia-based cream for prevention of adjuvant radiotherapy skin damage in mammary carcinoma: a randomized placebo controlled trial. Eur Rev Med Pharmacol Sci. 2015 Apr;19(8):1338-44.

Wang H, Syrovets T, Kess D, et al. Targeting NF-KB with a natural triterpenoid alleviates skin inflammation in a mouse model of psoriasis. J Immunol. Oct 2009;183(7):4755-63.

Wang R, Wang Y, Gao Z, Qu X. The comparative study of acetyl-11-keto-beta-boswellic acid (AKBA) and aspirin in the prevention of intestinal adenomatous polyposis in APC(Min/+) mice. Drug Discov Ther. 2014 Feb;8(1):25-32.

Weber CC, Reising K, Müller WE, et al. Modulation of Pgp function by boswellic acids. Planta Med. 2006 May;72(6):507-13

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

Yu G, Xiang W, Zhang T, Zeng L, Yang K, Li J. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. BMC Complement Med Ther. 2020 Jul 17;20(1):225.