Taxonomical Investigation, Chemical Composition, Traditional Use in Medicine, and Pharmacological Activities of Boswellia sacra Flueck

Aromatic oleo-gum-resin secreted from B. sacra, reputed as frankincense, is widely used in traditional medicine to treat Alzheimer's disease, gastric disorders, hepatic disorders, etc. Frankincense is also used in the cosmetic, perfume, and beverage and food industries. Frankincense is a rich resource for bioactive compounds, especially boswellic acids and derivatives. Although several reports have described frankincense's constituents and pharmacological activities, there is no comprehensive study that covers the valuable information on this species. Therefore, the current review will focus on the phytochemistry, traditional uses, and pharmacological activities of B. sacra.


Introduction
Boswellia sacra Flueck is a perennial plant belonging to the family Burseraceae. Aromatic oleo-gum-resin extracted from B. sacra, known as frankincense or olibanum (Figure 1), is used as a home remedy, especially in Middle East countries [1]. Frankincense is harvested by making shallow incisions into the tree trunk [2]. Frankincense is used in many industries such as cosmetic, pharmaceutical, beverage, food, detergents, and perfume industries [3,4]. e oleo-gum resin of B. sacra has many uses for the human body, including analgesic, hepatoprotective, anticoagulant, antioxidant, tumor-suppressive, anti-inflammatory, cardioprotective, Alzheimer's disease, gastric, hepatic, and skin disorders [5,6]. B. sacra is an important source of bioactive compounds, including terpenoids which have a wide range of biological activities [6]. e most important compounds found in resin from Boswellia sacra are boswellic acids and their derivatives, which are responsible for a number of medicinal properties belonging to the plant.
Accordingly, this review introduces B. sacra as a valuable herbal source in different industries such as pharmacy and food. [7,8]. Species of the genus, known as frankincense trees (olibanum), produce a resin gum traditionally harvested by making incisions on the trunks of the trees; as the resin is exposed, it darkens and hardens before being removed from the incision [9]. Among the species of the genus, only B. serrata Roxb. and B. sacra Flueck have economic importance. e taxonomy of Boswellia (five species) except B. papyrifera (Del.) Hochst. in northern Somalia and southern Arabia has been revised. erefore, the two extreme populations of Boswellia spp. vary in habitat, indumentum and shape of leaflets, number of inflorescence branches, and shape of fruits. ere are also populations showing the intermediate characteristics of the extremes in Somalia and the Arabian Peninsula. Based on flower and fruit features, B. sacra is closely related to B. papyrifera. e genus has been reduced to two species, including B. sacra Flueck and B. frereana Birdwood. Based on morphological data, B. carterii Birdwood has been synonymized with B. sacra [10]. However, recent chemical analysis has shown that these are distinct species [11]. To confirm this data, further taxonomical research is required. B. sacra is typified as follows: Boswellia sacra Flueckiger, Lehrbuch der Pharmakognosie des Pflanzenreiches [12]. B. sacra is a tree with a distinct trunk that grows to a height of 1.5-8 m. e stems branch from the base, having pale yellowish-brown bark. e young stems can be either hairy or smooth. Resin is copious on the bark. It is milky when first exposed, then pale yellowish when dried. Leaves are densely crowded, arranged as alternates and imparipinnate with 13-19 leaflets. e inflorescence is either raceme or panicle. e flowers emerge synchronously with leaves. Pedicel length is 2-8 mm, covered with sparse hairs or smooth. Calyx is cup-shaped; the color is reddish-brown and reaches between 2 and 2.5 mm in length. Petals are white and elliptic, and the dimension is 4-5 × 2-2.5 mm. Stamens are numerous, approximately 10. e filament texture is smooth; the length is 2.5-3 mm. e anthers are oblong and white. e texture can be hairy or smooth. e length is 0.8-1.4 mm. e flowers are yellowish to orange. e pistil is furrowed, smooth, and 2.5-3 mm in length. e fruit is pyriform, reddish-brown, and has 3-4 locules. e dimension is 8-12 × 3.5-9 mm. Pyrenes are trigonous and often surrounded by a persistent wing. e dimension is 3.5-5.5 × 2-4.5 mm.
Carter first collected this species from Arabia [13]. He incorrectly named the species as B. thulifera and B. serrate. Flueckiger [14] identified it as B. papyrifera and later correctly identified it as a new species "B. sacra" in 1867 [10].
B. sacra is mainly a saxicolous species. e cushion or disklike swelling base of the trunk adheres the plant to the rock faces. is plays an important role in stabilizing the plant, especially in very steep terrain. is species is distributed in Somalia, most parts of the Horn of Africa, and up to the Arabian Peninsula [15]. e plant growing in control and wild habitats is shown in Figure 2.

Traditional Medicine
e resin of frankincense is commonly used to treat bronchial and urinary infections. It is used as a rejuvenating medicine and treats menstrual pain, mouth problems, wounds, sores, ulcers, carbuncles, hemorrhoids, inflammation, and throat problems in some Asian countries. It is also known that frankincense oil has carminative, digestive, and diuretic properties.
is gum resin's water extract, known as "Moh-Lubban," is traditionally used to treat coughs and stomach problems [1].
In Oman, B. sacra gum extracts have long been used in various folk medicines for strengthening and stimulating the digestion process, dental infections, and for the treatment of colds, cough, muscle pain, fever, and asthma, as well as different types of cancer [16,17]. In Arabian folk medicine, the gum resin is reputed to improve memory [18].

Boswellic Acids and
Derivatives. e primary active components from the extract of B. sacra are boswellic acids (BAs). As shown in Figure 7, BAs are a group of oleanane or ursane pentacyclic triterpenoids with carboxylic acid at C-4 and are divided into two groups, β-BAs (ursane-type) and α-BAs (oleanane-type). eir potency against inflammation, arthritis, ulcerative colitis, chronic colitis, asthma, and hepatitis is well documented. ey also have exhibited antimicrobial, antidiabetic, antiviral, and antipruritic activity. One of the important uses of BAs in medicine is as an anti-inflammatory. Boswellic acids suppress leukotriene biosynthesis in neutrophilic granulocytes by nonredox, noncompetitive inhibition of 5-lipoxygenase [32,[35][36][37]. e pharmacological effects of B. sacra extract are commonly explained by the presence of boswellic acids [36]. Also, the anticancer activity of BAs is remarkable. In this regard, they have activity against cancers including bladder, brain, cervical, colon, colorectal, liver, leukemia, lung, melanoma, meningioma, multiple myeloma, neuroblastoma, ovarian, pancreatic, and prostate [38].

Standardization
e used part of the plant is an oleo gum resin that is easily found in herbal stores. For standardization of the oleo gum resin, boswellic acids and their derivatives have been accounted as standard markers [1].

B. sacra Products
ere are B. sacra essential oils as liquid form, for example in 10 ml bottles (Figure 9).

Anticancer Activity.
e essential oil of B. sacra has been found to induce breast cancer cell-specific cytotoxicity. B. sacra essential oil can suppress tumor aggressiveness in drug-resistant and cultured metastasized human breast cancer cells. B. sacra showed proapoptotic, antiproliferative, and anti-invasive properties in human breast cancer cell lines [39]. Essential oil from B. sacra suppresses viability and induces apoptosis in human pancreatic cancer cell lines. Frankincense essential oil activates the caspase-dependent apoptotic pathway, Akt and Erk1/2 signaling molecules and suppresses the levels of cyclin D1 (an important cell cycle regulator) expression in human pancreatic cancer cells.

Evidence-Based Complementary and Alternative Medicine
Essential oil of B. sacra gum resin has been suggested as a useful alternative therapeutic agent for patients with pancreatic adenocarcinoma, the major type of aggressive pancreatic cancer [40]. Besides, another study proposed that the essential oil was potent against colon cancer cells such as CD133+ and CD133-Colo-320 cells, and it was also considered that essential oil obtained from B. sacra led to a reduction of β-catenin signaling molecules which have a vital role in cancer cell proliferation [41]. In a case report study, oral administration of B. sacra gum resin was reported to be effective in urothelial cell carcinoma [42].

Analgesic Effects.
e analgesic effects of crude extracts and fractions of Omani frankincense obtained from B. sacra were studied in two mouse models of pain. Administration of the extract, essential oils, and subfractions from the resin of B. sacra in acetic acid-induced writhing and formalin tests demonstrated the antinociceptive properties of B. sacra as a traditional medicinal plant [16].

Hepatoprotective Effects.
Biological evaluations of cembrane-type diterpenes isolated from B. sacra showed that some of these compounds exhibited obvious hepatoprotective effects against paracetamol-induced HepG2 cell damage [26]. Administration of the water extract of oleo-gum-resin of B. sacra in rats demonstrated that this plant possesses hepatoprotective activity against carbon tetrachloride-induced acute and chronic hepatic damage [43].

Antimicrobial Effects.
Essential oils from B. sacra have been traditionally used to treat microbial and fungal infections. In vitro study of monoterpenoids of B. sacra essential oil showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Propionibacterium acnes. Frankincense essential oils also exhibited a significant antifungal effect against Candida albicans and Malassezia furfur [2]. e inhibitory effect of different concentrations of B. sacra resin, leaf extract, and essential oil has been evaluated on the growth and production of aflatoxins by Aspergillus flavus and Aspergillus parasiticus.
is study revealed that the resin powder and essential oil of B. sacra markedly reduce aflatoxin production. erefore, the resin powder and essential oil of B. sacra can be recommended as safe natural food preservatives to increase the shelf life of food and feed products with reference to their antimicrobial and aflatoxin inhibitory activities [44]. In another study, it was found that B. sacra oleoresin extract has a promising antibacterial and antibiofilm activity against Porphyromonas gingivalis [45]. Moreover, the potential of B. sacra extract was evaluated against a number of human gastrointestinal bacterial pathogens and autoimmune disease-stimulating bacteria in combination with conventional antibiotics. In this regard, the obtained results confirmed that the combination of conventional antibiotics with B. sacra extracts exhibited extremely higher activity than that of the individual components alone [46]. Recently, a research study revealed that B. sacra essential oil exhibited promising antifungal activity against some fungi species which lead to strawberry rot such as Botrytis cinerea, Aspergillus niger, and Rhizopus stolonifera [47].

Antioxidant Effects.
It has been shown that the essential oil of B. sacra gum resin has a strong antioxidant effect in the DPPH radical scavenging method. However, its antioxidant activity is lower as compared to the antioxidant property of ascorbic acid [48]. e effect of B. sacra oleo gum resin extract has been studied against testicular toxicity in rats. e extract of this plant decreased the gene expression of HSP70 (heat shock protein-70), GSTPi (glutathione-s-transferase-Pi), and IGFBP3 (insulin-like growth factor binding protein-3) in the testes. e result of this study suggests that the antioxidant effect of B. sacra may protect the testes against several toxicants through the inhibition of free radicals [1]. Moreover, recent evidence indicated that incorporation of B. sacra essential oil into nanoparticles enhanced the efficacy of some pharmacological properties such as antioxidant activity [49].

Anti-Alzheimer Effect.
e genus Boswellia has been suggested to cure or prevent neurodegenerative disorders through anti-inflammatory, antioxidative, antiamyloidogenic, and antiapoptotic effects [50]. Evaluating the effect of essential oil obtained from resins of B. sacra showed that frankincense essential oil can significantly inhibit the acetylcholinesterase enzyme (AChE). Inhibition of AChE leads to increased acetylcholine levels in the brain and improves memory in Alzheimer's disease patients. erefore, B. sacra as a medicinal plant may protect against memory loss from Alzheimer's disease [51].

Anti-Inflammatory Effect.
e anti-inflammatory effects of essential oil from B. sacra have been studied on an ovalbumin-induced allergic asthma mouse model. e results of this evaluation showed that inhalation of B. sacra essential oil has a potential therapeutic effect in allergic airway inflammation through increasing 1 cytokine (IFN-c) and decreasing 2 cytokines (IL-4, IL-5, and IL-13) levels [52]. 7.8. Antiseizure Effect. More recently, Wolfender and coworkers reported a comprehensive study on the antiseizure activity of resin of B. sacra. Results of this study demonstrated that among all isolated terpenoids, β-boswellic acid which belongs to triterpenoid derivatives was the most active and resulted in a 90% reduction of pentylenetetrazole (PTZ)induced seizures at 100 μg/mL [53]. e pharmacological activity of B. sacra gum resin and its phytochemicals is summarized in Table 1.

Future Perspectives
It is strongly believed that detailed information on the phytochemical and biological activities of B. sacra, as presented in this review, provides certain evidence for the use of  Further studies should be focused on the mechanisms behind the anti-inflammatory and memory improvement activities and those biological activities that have been reported traditionally.

Conclusion
is present work was designed to show that B. sacra is a valuable medicinal plant and an interesting subject to researchers. Many studies have indicated that B. sacra is a rich source of terpenoid compounds, especially triterpenoids, responsible for a wide range of biological activities. Although different studies have investigated these, there is no data on the clinical effectiveness of B. sacra. e findings of this review study on B. sacra suggested that clinical trial studies should be undertaken to explore the anti-inflammatory activity and memory improvement effects. B. sacra has a long and brilliant history in traditional medicine, and that is why clinical trial studies are strongly recommended for its drug development.

Conflicts of Interest
e authors declare that they have no conflicts of interest.