DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20214499

Efficacy of standardized novel Boswellia serrata extract in the dextran sodium sulfate-induced colitis model - potential use in gut health management

Shefali Thanawala, Rajat Shah, Prasanna Katnapally, Upendra Bhatnagar

Abstract


Background: Objective of this study was to evaluate anti-inflammatory properties of a novel standardized Boswellia serrata extract–bsRx (developed using natural excipients and designed to have specific ratio of its major actives, viz. AKBA and BBA) in dextran sodium sulfate (DSS)-induced IBD model in BALB/c mice.

Methods: Animals (BALB/c mice) in control (CL) group were administered vehicle; DSS-induced colitis group (DSS group), 2.5 % DSS; and Boswellia serrata group (BS group) received DSS, for inducing colitis, together with a novel standardized extract of Boswellia serrata (41 mg/kg, 4.1 mg/ml solution in distilled water) for 10 days. Reference group (SS group) received DSS with sulfasalazine (30 mg/kg, 3.0 mg/ml suspension in distilled water) for 10 days. Clinical assessment for disease activity index (DAI), histopathological examination and hematological assessments were performed.

Results: Treatment with Boswellia serrata showed significant reduction in the DAI score on day 10 compared to the DSS group (2.49±0.93 versus 3.63±0.55, p≤0.05). Body weight (18.54±2.21 gm versus 17.05±3.53 gm) and colon length (6.8±0.9 cm versus 7.6±0.6 cm, p≤0.05) also improved in the BS group compared to DSS group, respectively. Histological scoring of colitis was lower in the BS group (10.1±1.37). There was no difference in leukotriene levels between groups (p>0.05).

Conclusions: Treatment with novel Boswellia serrata extract improved colon length, DAI and histological scoring index in DSS-induced colitis in IBD mice models. Our results indicate the promising potential of novel Boswellia extract in IBD and gut health management.


Keywords


Colitis, Boswellia serrata, Boswellic acids, IBD, Anti-inflammatory, Gut health, AKBA

Full Text:

PDF

References


Alatab S, Sepanlou SG, Ikuta K, Vahedi H, Bisignano C, Safiri S, et al. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5(1):17-30.

Loddo I, Romano C. Inflammatory bowel disease: genetics, epigenetics, and pathogenesis. Front Immunol. 2015;6:551.

Dragasevic S, Stankovic B, Milosavljevic T, Sokic-Milutinovic A, Lukic S, Alempijevic T, et al. Genetic and environmental factors significant for the presentation and development of inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2017;29(8):909-15.

Leitner GC, Vogelsang H. Pharmacological-and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. World J Gastrointest Pharmacol Ther. 2016;7(1):5-20.

Weizman AV, Ahn E, Thanabalan R, Leung W, Croitoru K, Silverberg MS, et al. Characterisation of complementary and alternative medicine use and its impact on medication adherence in inflammatory bowel disease. Aliment Pharmacol Ther. 2012;35(3):342-9.

Hartmann RM, Fillmann HS, Martins MI, Meurer L, Marroni NP. Boswellia serrata has beneficial anti‐inflammatory and antioxidant properties in a model of experimental colitis. Phytother Res. 2014;28(9):1392-8.

Beghelli D, Isani G, Roncada P, Andreani G, Bistoni O, Bertocchi M, et al. Antioxidant and ex vivo immune system regulatory properties of Boswellia serrata extracts. Oxid Med Cell Longev. 2017;7468064.

Bertocchi M, Isani G, Medici F, Andreani G, Tubon Usca I, Roncada P, et al. Anti-inflammatory activity of Boswellia serrata extracts: an in vitro study on porcine aortic endothelial cells. Oxid Med Cell Longev. 2018;2504305.

Ammon HP. Boswellic acids and their role in chronic inflammatory diseases. Adv Exp Med Biol. 2016;928:291-327.

Suva MA, Kheni DB, Sureja VP. Aflapin®: A novel and selective 5-lipoxygenase inhibitor for arthritis management. Indian J Pain. 2018;32(1):16-23.

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;20(1):225.

Murthy SN, Cooper HS, Shim H, Shah RS, Ibrahim SA, Sedergran DJ. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Dig Dis Sci. 1993;38(9):1722-34.

Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989;96(3):795-803.

Millar AD, Rampton DS, Chander CL, Claxson AW, Blades S, Coumbe A, et al. Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut. 1996;39(3):407-15.

Park YH, Kim N, Shim YK, Choi YJ, Nam RH, Choi YJ, et al. Adequate dextran sodium sulfate-induced colitis model in mice and effective outcome measurement method. J Cancer Prev. 2015;20(4):260-7.

Rajesh B, Fleming A, Ramchandra R, Rajesh S, Shilpesh D. Effect of Tribulus terrestris against inflammatory bowel disease. Int J Vet Sci. 2013;2(4):143-50.

Anthoni C, Laukoetter MG, Rijcken E, Vowinkel T, Mennigen R, Müller S, et al. Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis. Am J Physiol Gastrointest Liver Physiol. 2006;290(6):1131-7.

Riva A, Giacomelli L, Togni S, Franceschi F, Eggenhoffner R, Zuccarini MC, et al. Oral administration of a lecithin-based delivery form of boswellic acids (Casperome®) for the prevention of symptoms of irritable bowel syndrome: a randomized clinical study. Minerva Gastroenterol Dietol. 2019;65(1):30-5.

Notarnicola A, Maccagnano G, Moretti L, Pesce V, Tafuri S, Fiore A, et al. Methylsulfonylmethane and boswellic acids versus glucosamine sulfate in the treatment of knee arthritis: Randomized trial. Int J Immunopathol Pharmacol. 2016;29(1):140-6.

Riva A, Morazzoni P, Artaria C, Allegrini P, Meins J, Savio D, et al. A single-dose, randomized, cross-over, two-way, open-label study for comparing the absorption of boswellic acids and its lecithin formulation. Phytomedicine. 2016;23(12):1375-82.

Governa P, Marchi M, Cocetta V, De Leo B, Saunders PTK, Catanzaro D, et al. Effects of Boswellia Serrata Roxb. and Curcuma longa L. in an in vitro intestinal inflammation model using immune cells and Caco-2. Pharmaceuticals (Basel). 2018;11(4):126.

Gayathri B, Manjula N, Vinaykumar KS, Lakshmi BS, Balakrishnan A. Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO and MAP kinases. Int Immunopharmacol. 2007;7(4):473-82.

Kapil A, Moza N. Anticomplementary activity of boswellic acids—an inhibitor of C3-convertase of the classical complement pathway. Int J Immunopharmacol. 1992;14(7):1139-43.

Song YN, Zheng P. Efficacy and safety of tumor necrosis factor-α blockers for ulcerative colitis: A systematic review and meta-analysis of published randomized controlled trials. J Food Drug Anal. 2015;23(1):1-10.

Sarkate A, Dhaneshwar SS. Investigation of mitigating effect of colon-specific prodrugs of boswellic acid on 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in Wistar rats: Design, kinetics and biological evaluation. World J Gastroenterol. 2017;23(7):1147-62.

Hüsch J, Gerbeth K, Fricker G, Setzer C, Zirkel J, Rebmann H, et al. Effect of phospholipid-based formulations of Boswellia serrata extract on the solubility, permeability, and absorption of the individual boswellic acid constituents present. J Nat Prod. 2012;75(10):1675-82.

Lin YM, Fu Y, Hegde S, Tang Y, Radhakrishnan R, Shi XZ. Microsomal Prostaglandin E Synthase-1 Plays a Critical Role in Long-term Motility Dysfunction after Bowel Obstruction. Sci Rep. 2018;8(1):8831.

Jablaoui A, Kriaa A, Mkaouar H, Akermi N, Soussou S, Wysocka M, et al. Fecal serine protease profiling in inflammatory bowel diseases. Front Cell Infect Microbiol. 2020;10:21.

Latella G, Sferra R, Vetuschi A, Zanninelli G, D'Angelo A, Catitti V, et al. Prevention of colonic fibrosis by Boswellia and Scutellaria extracts in rats with colitis induced by 2, 4, 5‐trinitrobenzene sulphonic acid. Eur J Clin Invest. 2008;38(6):410-20.

Kiela PR, Midura AJ, Kuscuoglu N, Jolad SD, Sólyom AM, Besselsen DG, et al. Effects of Boswellia serrata in mouse models of chemically induced colitis. Am J Physiol Gastrointest Liver Physiol. 2005;288(4):798-808.

Krieglstein CF, Anthoni C, Rijcken EJ, Laukötter M, Spiegel HU, Boden SE, et al. Acetyl-11-keto-β-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis. Int J Colorectal Dis. 2001;16(2):88-95.

Khanna R, Marshall JK. Sulfasalazine and 5-Aminosalicylates for Ulcerative Colitis. In: Baumgart DC, editor. Crohn's Disease and Ulcerative Colitis. 2017;389-97.

Alluri VK, Kundimi S, Sengupta K, Golakoti T, Kilari EK. An Anti-Inflammatory Composition of Boswellia serrata Resin Extracts Alleviates Pain and Protects Cartilage in Monoiodoacetate-Induced Osteoarthritis in Rats. Evid Based Complement Alternat Med. 2020;7381625.

Krüger P, Daneshfar R, Eckert GP, Klein J, Volmer DA, Bahr U, et al. Metabolism of boswellic acids in vitro and in vivo. Drug Metab Dispos. 2008;36(6):1135-42.

Roy NK, Parama D, Banik K, Bordoloi D, Devi AK, Thakur KK, et al. An update on pharmacological potential of boswellic acids against chronic diseases. Int J Mol Sci. 2019;20(17):4101.

Qurishi Y, Hamid A, Zargar MA, Singh SK, Saxena AK. Potential role of natural molecules in health and disease: Importance of boswellic acid. J Med Plant Res. 2010;4(25):2778-86.

Borrelli F, Capasso F, Capasso R, Ascione V, Aviello G, Longo R, et al. Effect of Boswellia serrata on intestinal motility in rodents: inhibition of diarrhoea without constipation. Br J Pharmacol. 2006;148(4):553-60.

Gupta I, Parihar A, Malhotra P, Gupta S, Lüdtke R, Safayhi H, et al. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med. 2001;67(5):391-5.

Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges R. Therapy of active Crohn disease with Boswellia serrata extract H 15. Z Gastroenterol. 2001;39(1):11-7.

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