Introduction

Inflammatory bowel disease (IBD) has a significant economic and health impact on communities worldwide and a considerable effect on patients' quality of life. Presently, IBD is reported to affect 6.8 million people worldwide, and the burden is expected to increase further.¹ IBD symptoms include chronic diarrhea, abdominal pain, rectal bleeding, and alteration in gut motility.² The pathogenic cascade of inflammatory reactions in the gut is enhanced by increasing reactive oxygen species (ROS) and pro-inflammatory mediators such as nitrogen metabolites, eicosanoids, chemokines, and cytokines.³ Traditional anti-inflammatory medicines like 5-aminosalicylic acid (5-ASA) and sulfasalazine; immunosuppressants like azathioprine and corticosteroids; and biological therapy using anti-tumor necrosis factor (TNF) medications are among the current IBD treatments.³ However, despite their superior efficacy, the frequency and severity of side effects, unmanageable dosage regimen and higher cost limit their long-term use. Furthermore, due to the pathologic heterogeneity of IBD, single-target therapy may not be effective. Therefore, establishing an alternative therapy option that addresses multiple therapeutic targets may provide higher efficacy, ease of administration, and fewer side effects. As a result, complementary and alternative medicine (CAM) has emerged as a novel approach for managing gastrointestinal disorders and improving and maintaining gut health.

Several studies have shown that nearly half of individuals with IBD are currently using CAM therapies or have used them in the past.⁴ Among the various complementary therapies available, botanical products have potential relevance because they have a long history of traditional use and are made up of multiple phytoactive agents that can simultaneously target inflammatory response pathways, providing a more comprehensive approach to disease management.³ Boswellia serrata is one such ingredient which is found to be effective in IBD and Irritable bowel syndrome (IBS) and has potential to be used for overall gut health management.

Boswellia serrata – the effective ingredient for IBD, IBS and gut health

The Ayurvedic system of medicine has been using Boswellia serrata for ages. It consists of oleo-gum resin obtained from the incision made on the trunk of the tree Boswellia serrata belonging to the family Burseraceae.⁵ The semi-solid gum exudate consists of gum resin that hardens slowly into an amorphous tear-shaped product with an aroma.⁶

The traditional plant Boswellia serrata is native to India.^7-9 The anti-inflammatory and analgesic properties of Boswellia oleo gum resin have been known since ancient times. It has been used to treat bronchial asthma, osteoarthritis, rheumatoid arthritis, and Crohn’s disease (CD).¹⁰ In addition, pleiotropic properties of Boswellia such as antioxidant, antiulcer, hepatoprotective, wound healing, analgesic, and anticancer activities are also studied for therapy and prevention.^8-11 Several clinical trials on the herb's anti-inflammatory effects have recently been published.¹² However, little progress has been made in investigating Boswellia serrata's therapeutic potential in gastrointestinal disorders such as inflammatory bowel disease (IBD) and ulcerative colitis (UC) and its role in gut health.³

Properties of Boswellia

The resinous part of Boswellia serrata contains monoterpenes (α-thujene); diterpenes, triterpenes, tetracyclic triterpenic acids, pentacyclic triterpenic acids (boswellic acids).¹³ Boswellia extract reportedly reduced the number of reactive oxygen species (ROS) caused by H2O2 by 25%.¹⁴ 3 - acetyl - 11 - keto - beta - boswellic acid (AKBA) is a leukotriene synthesis inhibitor that acts directly on 5-lipoxygenase.⁷ Boswellia serrata also inhibits nitric oxide production, and down regulates pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, and the complement system by inhibiting C3-convertase activity.^15,16 Inhibition of TNF-α and its signaling pathways has been identified as a highly effective method for managing ulcerative colitis.¹⁷ AKBA also inhibits the P-selectin-mediated recruitment of inflammatory cells protecting the intestinal epithelial barrier from inflammatory damage, suggesting it is an effective alternative for managing gut health (Figure 1). ³

Limitations of Boswellia serrata

The pharmacokinetic profile of Boswellia serrata showed low absorption, particularly for the most potent Boswellic acids, 11-keto-beta-boswellic acid (KBA), 3-acetyl - 11- keto -beta-boswellic acid (AKBA) and b-boswellic acid (BBA). Furthermore, it was found that KBA undergoes substantial phase I metabolism which hampers the overall efficacy of the herb. Thus, the efficacy of Boswellia serrata extract can be enhanced by increasing the bioavailability of AKBA and other Boswellic acids.¹⁹ Unfortunately, due to bioavailability issues, the standard Boswellia extract products have been unable to achieve higher efficacy in both in vivo models and clinical studies. In order to overcome this limitation, a novel Boswellia extract, bsRx was developed. The content of AKBA and BBA in commercially available products vary greatly. However, bsRx is standardized in specific ratio of its major actives, viz. AKBA and BBA to consistently provide significant therapeutic benefits. Additionally, bsRx is developed using natural excipients further contributing to the product’s long-term safety.³

Pre-Clinical Study of Boswellia for Management in Gut Health

The anti-inflammatory properties of this novel Boswellia extract, bsRx were studied in dextran sodium sulfate (DSS)-induced IBD mice model for ten days.³

Figure 2. A comparative graph showing the effect of standardized extract of novel Boswellia serrata extract on (a) colon length, (b) disease activity index, and (c) histopathology score at day. 10³

Treatment with bsRx inhibited the adverse impact of DSS on colon length, body weight, and showed a dose-dependent significant decrease in disease activity index (DAI) and significant attenuation of the tissue injury scores attributed to particular ratios of AKBA and BBA in the test product (Figure 2). Thus, bsRx showed enhanced colon length, DAI, and histological scoring index in DSS-induced mouse models of UC, which directly and positively impacted mortality.³

Clinical Trial on the effect of Boswellia serrata on irritable bowel syndrome (IBS)

A randomized, double-blind, placebo-controlled, parallel study evaluated the safety and efficacy of this novel formulation of Boswellia serrata extract 200 mg capsules in subjects having IBS. The primary efficacy endpoint was change from baseline to end of treatment in the IBS symptom severity scale (IBS-SSS). There was a statistically significant difference noted in mean change (reduction) in IBS-SSS from baseline to Week 12 in both treatment groups (p-value <.0001).
The secondary efficacy endpoints were changed from baseline in the gastrointestinal symptoms associated with IBS using the gastrointestinal symptom rating scale

(GSRS-IBS), change in symptoms of reflux and dyspepsia (QoL-RAD), and change in the abdominal pain, IBS quality of life (IBS-QoL) and gut microbiota population. A statistically significant reduction was noted in the mean change in GSRS-IBS, IBS-QoL, and QoL-RAD from baseline to week 12 in Boswellia group as compared to the placebo group. Moreover, a statistically significant improvement was noted in the gut microbiota population (Actinobacteria and Lactobacillales) from baseline to Week 12 in Boswellia group

Safety and toxicity Profile of Boswellia serrata Extract

During the trial, no serious, long-term adverse effects were observed. In addition, Boswellia serrata extract was well tolerated in the trial population.

Key Take-Away Message

• The anti-inflammatory and analgesic properties of Boswellia oleo gum resin have been known since ancient times. It has been used to treat bronchial asthma, osteoarthritis, rheumatoid arthritis, ulcerative colitis, and crohn's disease.⁶
• The therapeutic potential of Boswellia serrata in the gastrointestinal conditions such as IBS and ulcerative colitis, and its role in the management of gut health has been proven.
• Treatment with novel Boswellia serrata extract improved colon length, DAI and histological scoring index in DSS-induced colitis in IBD mice models.
• In the double-blind placebo controlled clinical trial, there was statistically significant improvement observed with novel Boswellia serrata extract 200 mg capsules in subjects with IBS. Novel Boswellia serrata extract 200 mg capsules are safe and well tolerated.
• This novel formulation of Boswellia serrata (200mg dose) provides high bioavailability with a high concentration of major Boswellic acid (AKBA) and a unique ratio of AKBA and BBA.
• With high bioavailability, the novel formulation reaches therapeutic potential with one capsule per day, thus leading to better convenience and compliance for the treatment.

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