Anti-Inflammatory and Antiviral

## **Chapter 9**

## Medicinal Plants as Sources for Drugs and Vaccines

*Siham A. Salim*

## **Abstract**

In general, vaccines are important biological factors that stimulate human immunity to resist various diseases or their pathogens that invade him. The vaccine includes protein material of the pathogen itself, which is either killed or weakened form, or is made from corresponding artificial protein subunits to help human's immune system for recognizing antigens. However, it has been observed that there are some side effects appeared from using of traditional vaccines, which made trending toward finding alternative solutions is an important goal. In recent years, with the progress in medicinal sciences, genetics and plant biotechnology, the concept of edible vaccines has emerged by biotechnologists in an attempt to use edible plants in the production of alternative vaccines for commercial vaccines that are useful in treating diseases that affect humans without needing for injection or refrigerated storage, which is done through genetically engineering plants to carry antigens through several methods, like bacterial vectors, shot gun or microinjection through plant tissue culture techniques to produce vaccine-bearing plants like banana, maize, potato, rice, tobacco, tomato, legumes and others which makes these plants have two tasks, their suitability for food and to stimulate the body's immune response against many pathogens at once.

**Keywords:** medicinal plants, immunization, natural drugs, edible vaccines, transgenic plants, vaccination

## **1. Introduction**

Vaccination is a simple, safe, and effective way to protect people from harmful diseases before they are exposed to them via induction of the body's natural defenses to build resistance to specific diseases, as well as strengthen the immune system. Vaccines train the immune system to make antibodies (proteins that the immune system naturally produces to fight disease), just as it does when exposed to a disease, as it recognizes an invading pathogenic organism, such as a virus, bacteria, or others, and fights it. However, because vaccines contain only dead or weakened forms of germs such as viruses or bacteria, they do not cause disease and do not expose the human body to the risk of complications, so most vaccines are given by injection, while others are given orally or sprayed into the nose to treat many diseases such as hepatitis B, measles, tuberculosis, tetanus, diarrhea, diphtheria, etc. [1].

Our immune systems have the ability to remember. Once exposed to one or several doses of a vaccine, we usually remain protected from the disease for years, decades, or even for life. This makes vaccines so effective, as they aim first to protect us from the disease before resorting to treatment after infection [2]. Although traditional vaccination is the safe method used around the world to confront the risk of diseases when exposed to them, it faces some limitations, represented by the cost of production, storage, distribution and the lack of sufficient scientific research on it. Therefore, scientists and researchers have turned to finding safe therapeutic alternatives under the progress made in various biotechnologies and genetic engineering, which made it possible to produce genetically modified plants, which prompted researchers to introduce antipathogenic genes into these plants in order to produce plants that are eaten and carry the anti-gene at the same time, which in turn are easy to transport, distribute and store so that they are available to humans when administered as edible vaccines [1, 3].

The concept of edible vaccines, plant-based edible vaccines, or plant-based vaccination appeared in the twentieth century. This is called a GreenVax (a concept developed in the 1990s, which means the consumption of edible tissues of transgenic plants), which refers to food, typically plants, that produce proteins, vitamins, or other nourishments that act as a vaccine against a certain disease. Once the plant, fruit, or plant-derived product is ingested orally, it stimulates the immune system. Specifically, it stimulates both the mucosal and humoral immune systems [4–6]. Edible vaccines offer many benefits over traditional vaccines due to their lower manufacturing cost and lack of negative side effects. However, there are limitations as edible vaccines are still new and developing. Further research will need to be done before they are ready for widespread human consumption.

The plant-based vaccine method works by isolating a specific antigen protein, which triggers a human immune response from the target virus. A protein gene is transferred to the bacteria, which is then used to "infect" plant cells. The plants then begin producing the exact protein that will be used for the vaccine [7]. The possibility of introducing a set of genes of human pathogens (whether viruses or bacteria) into plant cells, thus re-cultivating the plant again so that it can produce biological primary vaccines containing pathogen genes, and by feeding the tissues of these plants to humans or animals, an immune response to vaccines is elicited. The new process will only take 4–6 weeks. Depending on this, if the project succeeds, it will be one of the largest and most powerful vaccine facilities in the world. However, the development and widespread use of new vaccines to improve health conditions at the global level face many challenges. The cost of the new vaccine must be low, the vaccine must be administered orally without injection, and it must remain stable in high temperatures. It should also contain a combination of vaccines to prevent diseases prevalent in developing countries [8, 9].

## **2. Why the plant-based edible drugs and vaccines are important?**

Different drugs and vaccines were used in all countries of the world, as they caused a clear decrease in the death rates among humans, which are caused by various microbial infections with a large percentage, whereas in some cases vaccination leads to death of the vaccinated person [8]. The use of plants that are eaten to act as edible vaccines is an effective, safe alternative to traditional vaccines in controlling various types of diseases and illnesses [3, 10]. To obtain an edible vaccine, the required gene that encodes that active compound as a vaccine is selected and inserted into the desired plant, where this plant manufactures the proteins encoded for this vaccine to perform a systemic immune function that gives the required immunity to the body of the organism when the plant is eaten [11, 12].

#### *Medicinal Plants as Sources for Drugs and Vaccines DOI: http://dx.doi.org/10.5772/intechopen.113766*

Regardless of the way that edible vaccines are consumed, they all share an important common goal of immunizing the human body against different pathogens or before they multiply in quantities that are sufficient to cause disease and the appearance of disease symptoms in the patient. It is well known that the traditional methods of immunization against diseases are done by exposing the person's immune system to killed or very weakened bacteria or viruses [13]. Therefore, when the immune system becomes sensitive to any foreign organism in the vaccine, it will act as if the body is under attack and mobilize all of its forces to eradicate and destroy the attacker after targeting the antibody gene, which the immune system distinguishes as foreign proteins that have entered the body. In fact, there is a rapid suppression of the response, but it leaves behind a guard or a watchdog in the memory of the cells that remain fully prepared when the pathogen enters the body in the future, so some vaccines and serums provide the body with lifelong protection, and the other section fades after time, such as the cholera vaccine and the tetanus vaccine, which requires periodic immunization. It is noted that traditional vaccines have few risks, the most important of which is that the organisms with which the body was vaccinated may live and multiply inside the body, causing diseases that were supposed to be eliminated. From this aspect, most vaccine manufacturers today prefer another type of vaccine called subunit preparations, which consist mainly of antigenic proteins that have been discovered from the genes of the pathogens. Thus, there will be no possible chance for infection to occur in the future. Despite the importance of this modern industry of subunit vaccines, they are criticized for their high production costs due to their manufacture from bacterial cultures or animal cells, as well as their high purity and need for freezing.

The edible vaccines, which are the focus of our discussion, are similar to the subunit preparation in terms of being genetically engineered to ensure that they contain the antigen and do not contain the organism that causes the disease, and both are safe to use. Before starting the production of edible vaccines, scientists raised a number of questions, including whether plants that will be genetically modified to contain the antigen able to produce effective copies of the intended protein. Will the antigen transferred to edible plants be destroyed when consumed by humans or animals? Will the gene decompose in the stomach before it performs its role compared to subunit preparations that are given as injections to avoid their damage? Will the antigen that was produced alert the human or animal immune system, and will the immune system's response be sufficient to the extent of protecting humans or animals from infection with the disease against which they have been vaccinated? Besides that, researchers must know whether the edible vaccine appears in the mucosal immune system because many pathogens enter the body via the mouth, nose, reproductive organs, and others [14–16].

It is noted that when the response of the mucosal immune system is effective, molecules known as secretory antibodies are generated, which are released into the vacuoles of the orifices to resist the attack of pathogenic organisms that they find. An effective interaction may occur that activates the immune system in the body cells and thus kills the attacking pathogen. As it is known, vaccines injected into muscles avoid the mucous membranes, so the immune response to these membranes is weak, while edible vaccines come into contact with the internal walls of the digestive system, so it is assumed that they activate both the response of the mucous membranes and the systemic immunity in the body. It is assumed that this dual effect provides protection against dangerous microorganisms, especially those that cause diarrheal diseases, which prompted researchers to prioritize their research in combating

diarrhea causes first, then other pathogens, especially Norwalk Rotavirus [17, 18], against the *Escherichia coli* bacteria [19] that secrete internal toxins causing what is known as traveler's diarrhea, which leads to the death of nearly three million children annually in third world countries, and *Vibrio cholerae* (the bacteria that cause cholera) [20].

In fact, ideas began to circulate among many researchers from different countries of the world since 1995. For example, a gene encoding a protein was isolated from the virus that causes hepatitis B virus (causing liver damage and liver cancer) and transferred to the tobacco plant, which stimulated this plant to protein manufacturing. After injecting the antigen into the mice, it led to the activation of the components of the immune system of the mice to the same extent as what happens when they are infected with the hepatitis virus [21].

## **3. Methods of preparing the edible vaccine**

Several methods exist for genetically modifying plants to obtain edible vaccines, such as gen gun, vector system (bacteria), chimeric viruses, and electroporation (**Figure 1**).

The most important method adopted in the production of an edible vaccine is the vector carrier method, which depends on the *Agrobacterium tumefaciens* bacteria as an intermediate vector in the transfer of the genetic material (antigen proteins) from a virus or other bacteria to the target plant, which is embodied in the immune response of the organism after consuming calculated amounts of the antigen-bearing plant. This process is performed using plant tissue culture technology [22, 23]. It is also

**Figure 1.** *Schematic representation of various methods for developing an edible plant vaccine.*

## *Medicinal Plants as Sources for Drugs and Vaccines DOI: http://dx.doi.org/10.5772/intechopen.113766*

possible to insert the desired DNA into the plant genome by direct methods in plant genetic engineering. Perhaps it is easier to use the bombardment method by means of an gene gun after shooting it in the cultures of plant embryonic cell suspensions, because they are specialized into embryos, and it is easy to grow into a complete plant carrying the desired gene.

Regardless of how the plant is modified, the desired DNA randomly pairs with the plant's genome, producing different levels of antigen expression that differ from one plant to another. Thus, it is preferable to modify 50–100 plants at the same time, and each plant is considered a separate line, and through this number, the line (plant) that is more expressive of the antigen with less negative effects on the body is elected. The method of producing the edible vaccine using *A. tumefaciens* as an intermediate vector can be summarized in the following steps:

1.Vegetable leaves (leaves from the potato plant, for example, as shown in (**Figure 2**) are separated in good health condition, sterilized superficially, and cut into explants. When the cutting areas of the explant's edges increase, there is a greater chance of infecting them with bacteria carrying the required gene, and thus, the success of the genetic transformation process.

#### **Figure 2.**

*Schematic showing the method of potatoes-edible vaccine production using* Agrobacterium tumefaciens *as intermediate vector through plant tissue culture technique.*


Some of transgenic plants were invested to be consumed as edible vaccines, as shown in **Table 1**.

With the progress made in medical, agricultural, and pharmaceutical sciences, companies from different countries of the world produced vaccines from potatoes, tomatoes, lettuce, spinach, white clover, and Arabidopsis, where these plants were used as hosts for the production of vaccines [30, 31]. There has also been


**Table 1.**

*Some pharmaceutical substances that were derived from plants to treat some human diseases.*

*Medicinal Plants as Sources for Drugs and Vaccines DOI: http://dx.doi.org/10.5772/intechopen.113766*

progress in the use of plant species that are not edible plants but are medicinal plants and easy to handle in the laboratories for this purpose, such as Aloe vera plant [32], Neem plant [33], and *Chlamydomonas reinhardtii* green algae [34]. In general, each plant has its advantages and disadvantages if it is used as an edible vaccine.

## **4. Advantages of edible plant vaccines**

The most important advantages of plants that make them candidates for the production of edible vaccines:


## **5. Disadvantages of edible plant vaccines**




*Medicinal Plants as Sources for Drugs and Vaccines DOI: http://dx.doi.org/10.5772/intechopen.113766*

#### **Table 2.**

*Merits and demerits of plant species used as edible vaccines.*

4.Plants are living organisms that change in terms of growth and response to different environmental conditions, so there may not be a guaranteed continuity here for the production of a required edible vaccine.

## **6. Most important plant species used as edible vaccines**

As a result of the successes achieved from the expression of genes introduced into plants or their parts that are eaten, many plants that have been genetically modified have been produced and tested. **Table 2** shows the most important of these plants, their merits and demerits.

## **7. Conclusion**

It is clear from the above that for many decades, traditional vaccines were the important factors in stimulating the human immune system to resist many diseases that affect him or to become immune to any vectors of diseases, whether viruses or bacteria. However, on the other side, the manufacture of these vaccines required a lot of effort, research, and the high cost of production, storage, and distribution around the world, as well as the occurrence of some side complications for these vaccines.

This led many researchers in the past two decades to find alternative solutions by creating the idea of edible vaccines and heading toward achieving this through the production of edible plant vaccines, which include edible plant parts from fruits, seeds, or plant products to be on hand for consumption by people as food. On the one hand, to stimulate human immunity to resist diseases or pathogens by genetically modifying these plants to contain antigens that fight diseases, in addition to making them easy to cultivate, store, and distribute worldwide as plant products. However, the limitations on this issue are that the concept is new and is not widely accepted at present in developing countries, and the opposition to transgenic plants by injecting them with special genes to make them edible vaccines. This needs to be conducted in many studies in the future.

## **Author details**

Siham A. Salim Department of Biology, College of Education, Al-Iraqia University, Baghdad, Iraq

\*Address all correspondence to: dr.sihamabdalrazzaq22@yahoo.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Medicinal Plants as Sources for Drugs and Vaccines DOI: http://dx.doi.org/10.5772/intechopen.113766*

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## **Chapter 10**

## *Boswellia* Carries Hope for Patients with Inflammatory Bowel Disease (IBD)

*Sally Elnawasany*

## **Abstract**

*Boswellia serrata* is an ancient and valuable herb that was widely used throughout the centuries. *Boswellia* trees grow in India, Northern Africa, and the Middle East from which Frankincense or olibanum resin is taken. The beneficial effects of *Boswellia* and its active ingredients (Boswellic acids) were thoroughly investigated in many diseases. Where the non-redox and 5-lipoxygenase inhibitory actions were reported. Inflammatory bowel disease (IBD) mainly ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory disorders of the gastrointestinal system. Although the cause is still unclear, the immune system is claimed to have the upper hand in the pathogenesis of IBD. Several studies have demonstrated the ameliorating effect of Boswellic acids on the severity of IBD and the potential role of *Boswellia* in the induction or maintenance of remission. The aim of this chapter is to explore the the possible effect of *Boswellia* in IBD management as a complementary and alternative strategy.

**Keywords:** *Boswellia*, complementary and alternative medicine, inflammatory bowel disease, ulcerative colitis, Crohn's disease

## **1. Introduction**

Inflammatory bowel disease (IBD) is a chronic inflammatory state classified mainly into ulcerative colitis (UC) and Crohn's disease (CD). IBD is associated with abdominal pain, diarrhea and rectal bleeding [1]. The choice of treatment for IBD varies according to the type and severity. A variety of medications such as aminosalicylates, corticosteroids, immunosuppressive and biologic drugs are involved [2]. Despite their crucial therapeutic role, some medications carry the risk of infection and cancer [3]. In addition, these drugs are taken throughout life, which leads to patient incompliance and hence treatment failure [4]. These obstacles in treatment insist on the search for other treatments, safe and effective as alternative and complementary modalities.

## **2. Pathogenesis of IBD**

The exact mechanism of IBD is not completely clear [5]. The interaction between genetic factors, changes in intestinal flora homeostasis, environmental variabilities, and intestinal hyperimmune response results in chronic intestinal inflammation [6]. Multiple inflammatory mediators are involved in IBD pathogenesis including leukotrienes, cytokines, chemokines, and prostaglandins. Alteration in reactive oxygen and nitrogen species production adds to the pathogenesis [7]. Based on this, attenuation of hyper-stimulated immune response is the target of IBD therapy. Where the treatment passes in 2 ways, the first is to induce remission and the second is to maintain the remission and to ameliorate intestinal chronic inflammation [8]. In normal conditions, there is a balance among many cells in intestinal lamina propria such as macrophages mast cells, neutrophils, dendritic cells (DCs), eosinophils, natural killer (NK), NKT cells, T and B cells. This provides intestinal protection and tolerance. As a response to bacterial infection, the innate immunity cells (macrophages and dendritic cells) upregulate chemokines and cytokines and act as Antigen-presenting cells (APCs) where they feature the microorganism's molecular patterns via toll-like receptors (TLR) [9, 10]. Dendritic cells generate native T cell differentiation in mesenteric lymph nodes [11]. With subsequent generation of T helper (Th) subtypes according to the cytokines produced by APCs [12–15]. Besides proinflammatory cytokines induction, neutrophils stimulate oxidative reactions in the intestinal mucosa [16]. In IBD activity, there is over-expression of many chemokines including macrophage inflammatory proteins (MIP), and Interleukin-8 (IL-8). Under the control of these chemokines, leukocytes are recruited to the inflamed intestine with subsequent oxidative stress [17]. Recruitment of granulocytes and lymphocytes is mediated by adhesion molecules in IBD, such as the intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule- (VCAM-) 1, P and E-selectins [18]. In addition, T-cell differentiation and regulation are mediated by cytokines. Th1 differentiation is controlled by IL-12, IL-18, and IL-23 while TNF-α, IL-1β, and IL-6, magnify the immune response by releasing more chemokines and attracting more inflammatory cells [19]. On the other hand, the under-production of IL-10 and Transforming growth factor beta (TGF-β), which are inflammatory attenuating cytokines, contributes to IBD pathogenesis [20, 21].

## **3. Complementary and alternative (CAM) treatment of IBD**

There is a growing worldwide interest in complementary and alternative remedies in IBD treatment [22, 23]. The use of CAM is common for IBD children and adult patients [24, 25]. CAM is found to be commonly used among young, females, at a high educational level or with medication adverse effects [26, 27]. Patients who received massive corticosteroid therapy [28] or suffering from extraintestinal manifestations [24] are more inclined to CAM remedies, as well. Many alternative modalities have been tried in IBD patients including herbs, probiotics, acupuncture and hypnotherapy [8]. Phytochemicals are popularly utilized because of their safety and effectiveness on IBD patients [4, 29]. The variable active herbal ingredients which act on multiple inflammatory pathways and mediators support this preference [25]. *Aloe vera*, *Artemisia absinthium*, *Boswellia serrata* and *Curcuma longa* were widely studied for their effect on IBD [30].

## **4.** *Boswellia serrata*

#### **4.1 Structure of** *Boswellia serrata*

*Boswellia serrata* oleo-gum resin, Indian frankincense was widely used for centuries in traditional medicine. Antioxidant and anti-inflammatory actions have been

### Boswellia *Carries Hope for Patients with Inflammatory Bowel Disease (IBD) DOI: http://dx.doi.org/10.5772/intechopen.112244*

extensively investigated in several studies on different diseases like colitis, bronchial asthma, arthritis and malignancies [31–35]. *Boswellia serrata* resin is composed of monoterpenes, diterpenes, triterpenes, pentacyclic triterpenic acids (boswellic acids) and tetracyclic triterpenic acids [36–39]. Boswellic acids (BA) compose up 30% of the resin of *Boswellia serrata*. They are organic acids, formed of a pentacyclic triterpene, a carboxyl group and at least one other functional group [40]. Among boswellic acids*,* 11-keto-β-boswellic acid (KBA) and acetyl-11-keto-β-boswellic acid (AKBA) are the most active [41].

## **4.2 Pharmacological activities of** *Boswellia serrata*

## *4.2.1 Anti-inflammatory action*

*Boswellia* has variable pharmacological activities, anti-inflammatory properties were widely investigated in many studies. Acetyl-boswellic acids block leukotriene production through the downregulation of enzyme 5-lipoxygenase (5-LOX) mediated by a non-redox reaction [42, 43]. In a double-blind placebo control clinical study alcohol extract was given in a 300 mg thrice daily dose for 6 weeks. 70% of asthmatic patients gained clinical improvement [44]. Similarly, gradual control of asthma, regarding the frequency of attacks, pulmonary function tests improvement, and lowering levels of leukotrienes were obtained by another study [45]. In addition, *Boswellia* ameliorated the inflammation in arthritis [46–48]. Anti-anaphylactic and mast cell stabilizing effects were also reported where *Boswellia* suppressed mast cell degranulation [49]. Moreover, boswellic acids were found to possess anti-complement activity [50]. Roy et al. studied the genetic basis of anti-inflammatory effect of BA. Tumor necrosis factor alpha (TNFa) is one of the most crucial mediators of inflammation. TNF alpha induces inflammation by multiple mechanisms, one of them is by upregulation of the expression of adhesion molecules such as microvascular cellular adhesive molecul-1, VCAM-1 in a system of TNF alpha-induced gene expression in human microvascular endothelial cells (HMEC). Of 522 genes that were induced by TNFa 113 genes were highly sensitive to BE treatment both in vivo and in vitro. The function of these genes is linked to inflammation, and cell adhesion [51].

### *4.2.2 Anti-microbial action*

*Boswellia* oils showed anti-microbial activity against five organisms. Minimum inhibition concentration ranged from 4 to 16 mg/ml against *Staphylococcus aureus*, 1.5–8.3 mg/ml against *Bacillus cereus*, 4.0–12.0 mg/ml against *Escherichia coli*, 2.0– 12.8 mg/ml against *Proteus vulgaris* and 5.3–12.0 mg/ml against *Candida albicans* [52]. This effect may help in controlling intestinal infection in IBD management.

### *4.2.3 Anti-tumor action*

Boswellic acids induced apoptosis through the upregulation of caspase-8 in colon cancer HT-29 cells [53]. In another study, *Boswellia* extract altered DNA methylation in colon cancer cells [54]. 4-Amino analogues prepared from β-boswellic acid and 11-keto-β-boswellic acid showed an apoptotic activity mediated by DNA fragmentation [55]. There are multiple pathways by which *Boswellia* exerts its anti-tumor action such as suppression of topoisomerases I and II [56]. It was also revealed that acetyl keto beta boswellic acid (AKBA) inhibits phosphorylation of ERK pathways and

consequently, impairs signal transduction and tumorigenesis [57]. Oxidative stress and nitric oxide production were mediated by *Boswellia* with subsequent apoptosis in human leukemia HL-60 cells [58]. This anti-tumor potential of *Boswellia* protects against colorectal cancer which is a common sequala of IBD [59].

#### *4.2.4 Hepato-protective action*

In the models of liver injury, hexane extract of oleo-gum-resin of *Boswellia* in lower doses (87.5 mg/kg p.o.) reduced marker enzymes and prevented the increase in liver weight with histological evidence of hepatoprotection while a mild effect was obtained by higher dose (175 mg/kg p.o.) [60].

### *4.2.5 Anti-lipidemic action*

The aqueous extract of *Boswellia carterii* with other herbs improved the lipid profile of alloxan-induced diabetic rats [61]. *Boswellia* showed therapeutic potential for metabolic syndrome. Where *Boswellia* succeeded in lowering the lipid profile by decreasing the level of TNF-α, IL-1β and increasing the adiponectin level. This action is based on its antioxidant activity [62].

#### *4.2.6 Hypoglycemic action*

Herbal formulation containing *B. serrata* oleo-gum-resin induced a significant anti-diabetic activity on non-insulin-dependent diabetes mellitus [63]. Furthermore, a significant reduction in blood glucose levels and HbA1c was observed when *Boswellia serrata* was introduced for 17 days to diabetic rats in another study [64].

Based on the mentioned pharmacological actions, *Boswellia* can help in IBD in many ways, 5-lipoxygenase (5-LO) suppression, downregulation of Tumor necrosis factor alpha (TNF-α) and interleukins, P-selectin-mediated recruitment of inflammatory cells, decreasing reactive oxygen species (ROS), and by modulation intestinal motility [65–68].

#### **4.3 Preclinical studies of** *Boswellia* **in IBD**

In vitro study demonstrated the role of *Boswellia* in the suppression of leukotriene synthesis through interfering with 5-lipoxygenase pathway [69]. The anti-inflammatory effects of boswellic acids extended to inhibit the nuclear transcription factor kappa B (NF-κB) activation, this factor expresses and potentiates the proinflammatory cytokines including TNFα, IL-1β, and IL-6 [70, 71]. This effect was confirmed in an in vitro experimental model of intestinal inflammation where pretreatment of Caco-2 cells monolayers by *Boswellia serrata* oleo-gum extract (BSE) and AKBA abolished nuclear factor kappa B (NF-κB) activation, protected against cellular changes and inhibited reactive oxygen species (ROS) [72]. Furthermore, the anti-inflammatory and antioxidant properties of *Boswellia serrata* were explored in acetic acid (AA) induced UC rat model. Daily administration of 34.2mg/kg of *Boswellia serrata* extract pre- and post-induction of colitis significantly improved tissue lesions, decreased lipid peroxidation and nitric oxide [73]. A semisynthetic form of acetyl-11-ketoβ-boswellic acid ameliorated the disease activity and histology in dextran sodium sulfate (DSS) induced murine colitis. This action was mediated by attenuation of adherent leukocytes and platelets into inflamed tissue by blocking P-selectin

Boswellia *Carries Hope for Patients with Inflammatory Bowel Disease (IBD) DOI: http://dx.doi.org/10.5772/intechopen.112244*

stimulation [66]. In an in vitro model of intestinal inflammation, the anti-inflammatory action of *Boswellia serrata* and *C. longa* were tested. *Boswellia serrata* at 1 μg/mL protected the intestinal epithelium with a 25% reduction of ROS generation [74]. The immunosuppressive potential of *Boswellia carteri* gum resin extract was illuminated in an in vitro study, where the extract attenuated human primary T lymphocyte proliferation in a concentration-dependent manner via nuclear factor of activated T-cells (NFAT) dependent mechanism [75]. Metabolism of sphingomyelin induces lipid signals that impact cell proliferation, and inflammation. 3-acetyl-11-keto-β-boswellic acids (AKBA) attenuated the expression of sphingomyelinase in intestinal cells. This provides other anti-inflammatory mechanism of *Boswellia* [76]. A new herbal formulation that includes Punica granatum L, *Boswellia* serrata, and Curcuma longa L extracts, inhibited TNF-alfa-induced release of IL-8, IL-6 and Monocyte chemoattractant protein-1 (MCP-1) in Caco-2 cells [77]. Although many studies support the anti-inflammatory action of *Boswellia*, on the contrary, Kiela et al. claimed that *Boswellia* showed no effect on improving colitis in dextran sulfate sodium (DSS)- or trinitrobenzene sulfonic acid- (TNBS-) induced experimental models [78]. Antifibrotic effect of *Boswellia* was declared when oral *Boswellia* in combination with significantly improved the inflammation of trinitrobenzene sulphonic acid (TNBS) induced chronic colitis. There was an improvement in the histological features of colonic fibrosis. Together with a significant reduction in the expression of alphasmooth muscle actin (α-SMA), collagen I–III, connective tissue growth factor (CTGF) and transforming growth factor-beta1 (TGF-β1) [79].

## **4.4 Clinical studies of** *Boswellia* **in IBD**

*Boswellia serrata* in a dose of 350 mg thrice daily for 6 weeks achieved remission in 82% of treated UC patients compared to 75% of patients who were treated with sulfasalazine (1 g thrice daily). Inflammatory parameters were better in *Boswellia* treated group as well [80]. Another trial was conducted on 30 patients with chronic colitis for 6 weeks. Of 20 patients who received daily 900 mg *Boswellia serrata,* improvement of inflammatory parameters and remission were noticed in (18 and 14 patients, respectively) while after treatment of 10 patients with 3 gm sulfasalazine daily 6 participants showed improvement in inflammatory parameters and remission was achieved in 4 patients [81]. *Boswellia* tolerability and ability to maintain remission were demonstrated in a 52-week multicenter double-blind, placebo-controlled, randomized Germain study. 82 CD patients were randomly divided, 42 patients received daily *Boswellia* in 400 mg capsules and 40 patients received a placebo. There was no difference in both groups in parameters of inflammation or disease activity or maintaining remission and *Boswellia* was well tolerated [82]. Another 4-week trial was conducted on UC patients who were in remission. *Boswellia serrata* extract (BSE) was introduced orally, in a novel delivery form to 22 patients compared to 21 patients with no treatment. Improvement in clinical parameters, a decrease in medication needs and a lowering in fecal calprotectin levels were observed in *Boswellia* treated group [83]. The effect of *Boswellia* was tried in patients with collagenous colitis as well, where 400 mg oral BSE was given thrice daily for six weeks compared to a placebo. The remission rate was higher in BSE-treated patients but without any changes in histology or quality of life [34]. We conducted a 6-week clinical trial on 60 patients with active ulcerative colitis to investigate the effect of *Boswellia* extract on disease activity. 20 patients received Mesalamine 3, 20 patients received *Boswellia* extract in the form of oral tablets in a dose of 2 gm/day, and 20 patients were given *Boswellia*

extract plus Mesalamine in the mentioned doses. Clinical and laboratory improvement was noticed in the three groups without a significant difference. There were no recorded side effects of *Boswellia* during the 6 weeks of the study [84].

## **5. Conclusion**

Based on preclinical and clinical studies, the anti-inflammatory, immune modulation, and anti-cancer activities of *Boswellia* as well as its safety and tolerability recommend its therapeutic use in IBD patients.

## **Acknowledgements**

I thank God Almighty for his countless blessings, including *Boswellia*, and I thank my patients for their patience and trust. I extend my gratitude to Professor Dr. Farid Badria for his continuous support.

## **Conflict of interest**

I confirm that there are no conflicts of interest.

## **Author details**

Sally Elnawasany1,2

1 Tanta University, Egypt

2 Al-Rayan College, KSA

\*Address all correspondence to: elnawasany\_s@hotmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Boswellia *Carries Hope for Patients with Inflammatory Bowel Disease (IBD) DOI: http://dx.doi.org/10.5772/intechopen.112244*

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## **Chapter 11**
