INTRODUCTION:

Unknown in its genesis, rheumatoid arthritis (RA) is typified by inflammatory alterations in the synovial tissue of joints, bone, cartilage, and, less frequently, extra-articular locations. It has become clear in recent years that genetic and epigenetic factors have a role in the development of RA. Rheumatoid arthritis (RA) is a persistent polyarticular inflammatory arthritis that affects not only the small joints of the hands and feet but also the medium and big joints. It is associated with excessive disability, mortality, and morbidity. RA is a complex inflammatory and autoimmune disease with systemic involvement and symptoms¹

The primary aim of anti-inflammatory treatment for Osteoarthritis and Rheumatoid arthritis is to effectively alleviate pain and reduce inflammation while preventing joint degeneration, destruction, and deformities. Traditional approaches to relieve Osteoarthritis symptoms involve the use of non-selective cyclooxygenase II inhibitors, which, unfortunately, are associated with significant adverse effects. As a result, researchers are now investigating safer alternative treatments for osteoarthritis, such the use of several herbal remedies like Zingiber Officinalis (ginger), Boswellia serrata, and Curcuma longa (curcumin) proven ability to reduce inflammation².

Boswellia serrata is an oleogum resin that belongs to the Boswellia genus, within the Burseraceae family. This resin is obtained by making an incision in the trunk of the Boswellia tree. A liquid material gradually seeps out of the semisolid oleogum resin over the course of roughly a month. which is collected in bamboo baskets. As time passes, the residual gum resin undergoes solidification and can be found in various grades Resin makes up around 30–60% of oleogum resin, with essential oils making up the remaining 5–10%. Monoterpenes, diterpenes, and triterpenes are among the active substances found in the resinous portion of oleogum resin. Tetracyclic triterpenic acids, also referred to as Boswellic acids, and pentacyclic triterpenic acids are also present.³

1. Taxonomical characteristics:

Kingdom: Plantae

Phylum: Tracheophyta

Class: Magnoliopsida

Order: Sapindales

Family: Burseraceae

Genus: Boswellia

Species: B. serrata

Division: Spermatophyta

Sub division: Angiospermae

Tribe: Rosopsida

Botanical Name: Boswellia serrata Roxb.⁴

fig.1 : Boswellia serrata plant

Vernacular names:

Unani/Arabic: Kundur

Arabic: Luban

English: Indian frankincense

Hindi: Salai Kundur, Luban

Tamil: Parangisambrani

Telugu: Anduga, Kondagugi, Tamu

Persian: Kundur

Urdu: Kundur

Sanskrit: Kunduru, Ashwamuthri

Kannada: Gugula, Dhupa, Shallaki, Chitta, Adimar, Tallaki, Maddi

Trade name: Guggul, Salai (gum resin)⁵

Physiological Characters:

Color- White to Cream

Odor – Characteristic

Taste – Characteristic

Solubility: insoluble in water, 5mg/ml⁶

2. Morphology of Plant Boswellia serrate:

Boswellia serrata trees typically feature thin, papery bark. Their leaves are deciduous, alternate, and densely clustered at the branch tips. These leaves are imparipinnate, with opposite, usually serrated leaflets. The flowers are small, white, and hermaphrodite, arranged in auxiliary racemes. They have 3-5 petals that can be either free or occasionally fused, and they fall off as the flower matures. The plant typically has numerous stamens, either equal to or twice as many as the petals, often inserted at the base or margin of the disk, occasionally fused at the base. Filament-free staminodes are absent. Anthers are usually versatile, and each ovary contains two (very rarely one) ovules in each cell. The fruits are drupaceous, typically indehiscent, and contain 2-5 pyrenes or have a pseudo capsular dehiscent nature⁷

Fig. no. 2: Boswellia serrata plants parts

2.1 Leaves: These leaves are odd-pinnate and measure approximately 30–45cm in length. They lack stipules and exhibit variable shapes, but they are typically clustered at the ends of branches.⁸

2.2 Leaflets: There are usually 8–15 leaflets, each measuring 2.5–6.3 × 1.2–3.0cm. The leaflets are ovate or ovate-lanceolate in shape, with rounded bases. They are nearly sessile and often have short, serrated edges. Most of the time, they are covered in fine hairs (pubescent).^9,10,11

2.3 Flowers: These are bisexual and relatively small, appearing in white clusters in axillary racemes or panicles located at the tips of branches.

2.4 Calyx: The calyx consists of 5–6 lobes and is small and cup-shaped.

2.5 Petals: Petals are oblong-ovate, measuring approximately 0.5–0.8cm in length, and have a basal disk. They are typically white or pink.

2.6 Fruits: The fruits are cotyledonous, trifed (trifoliate), about 1.25cm long, trigonous, and obovoid in shape.

2.7 Seeds: The heart-shaped seeds are affixed to the fruit's inner angle. They are compressed and pendulous.^12,13

3. Preliminary Phytochemical Analysis:

Phytochemical analysis aims to detect and measure a range of bioactive compounds within Boswellia serrata. These compounds encompass triterpenoids, essential oils, flavonoids, and other constituents. Among these, triterpenoids, specifically the boswellic acids, are recognized as the primary active components responsible for the plant's anti-inflammatory and anti-cancer properties. In order to extract the phytochemicals from the plant material, extraction procedures must be applied in Boswellia serrata analysis.^14,15

Solvent extraction, supercritical fluid extraction, cold extraction, and hot extraction are some of the methods that may be used to isolate these bioactive compounds . These substances are identified and quantified using a variety of analytical techniques once they have been removed. Nuclear magnetic resonance (NMR) spectroscopy, high-performance liquid chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS) are some of these techniques.¹⁶

Table no.1 phytochemical screening of Boswellia serrata¹⁷

Sr. No	Phytochemical Name	Name of test	Inference
1.	Carbohydrate.	Molisch's test (General test) To 2-3 ml aqueous extract, add a small quantity of alpha naphthol solution in alcohol, shake, and add conc. H2SO4 from the side of the test tube	Present
2.	Amino Acid.	Test for Ninhydrin (General test) For 10 minutes, bring 3 ml of T.S. and 3 drops of 5% Ninhydrin solution to a boil in water.	Present
3.	Protein	Test Biuret (General test) Add 4% NaOH and a small quantity of 1% CuSO4 solution to 3 ml of T.S.	Present
4.	Lipid	Extract dropout on filter paper drought comes then lipids are present.	Absent
5.	Starch.	Test solution for iodine: Combine 3 millilitres with a small quantity of diluted iodine solution. The blue hue first appears, vanishes when it boils, and then returns when it cools	Absent
6.	Alkaloids	Wagner's test 2-3 ml filtrate with a small quantity of Wagner's reagent gives reddish brown ppt.	Present
7.	Flavonoids	Test Shinoda Add 0.5 g of magnesium turnings, a small quantity of concentrated hydrochloric acid, and 5 ml of 95% ethanol butyl alcohol to dry powder or extract. Orange, pink, red, and purple hues are seen.	Present
8.	Tannins	5% FeCl3 solution	Present
9.	Saponins	Shake the sample for 15 seconds after adding water.	Present
10.	Glycosides	Legal's test (Cardenoloid Test) Add one millilitre each of sodium nitroprusside and pyridine to an alcoholic or aqueous extract.	Present

4. Chemical Constituents:

The resinous component of Boswellia serrata has a range of chemical compounds along with four major pentacyclic triterpene acids: β-boswellic acid, acetyl boswellic acid, 11-keto-β-boswellic acid, and 3-acetyl-11-keto-β-boswellic acid.¹⁸

4.1Mechanisms of action

Boswellic acids (BAs) exhibit activity against various targets. They specifically affect 5-lipoxygenase (5-LO), topoisomerases, angiogenesis processes, and cytochrome P450 enzymes. Additionally, their effect on MAPK (mitogen-activated protein kinase), particularly p38, varies depending on the type of cell they influence. BAs can either stimulate or inhibit MAPK, contingent on the specific cellular context.

Moreover, it contributes to the suppression of 5-LO, Leukocyte Elastase, Topoisomerase, and C2 Convertase.¹²

5. Pharmacological Effects:

5.1 Anti-inflammatory and anti-Arthritis:

Boswellia serrata is renowned for its anti-inflammatory properties, and numerous studies have been undertaken to assess its effectiveness in this regard. Each of these studies consistently provides robust evidence supporting the plant's anti-inflammatory potential. For example, in a clinical trial by Kimmatkar et al.(13), The anti-arthritic effects of Boswellia serrata extract (BSE) were investigated in thirty patients with osteoarthritis of the knee. After the extract was administered, the results showed a decrease in knee joint swelling and related discomfort. After the course of therapy, several more favourable results were also observed.¹³⁰

5.2Anticancer or Antitumor:

One of the strongest naturally occurring anti-cancer compounds comes from boswellia. Using methanol, the gum resin exudates of Boswellin (BE) serrata were extracted; the gums included triterpenoids., including b-Boswellic acid and its equivalents .The primary components of boswellin, b-BA and its derivatives, have been shown by Huang et al.¹⁴ to possess anticarcinogenic, antitumor, and antihyperlipidemic properties. According to numerous studies, Boswellia contains pentacyclic triterpenes, which are among the most promising anticancer medications.

5.3 Anti-oxidant:

According to research conducted by Sharma et al.¹⁵, Boswellia serrata is used to make an aqueous extract that has antioxidant qualities. This extract has demonstrated effective scavenging activity against a variety of radicals, including superoxide, nitric oxide, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and hydroxide radicals. The extract showed that at 500 mg/mL, it might reduce as much as possible.¹⁵

Moreover, Boswellia serrata's antioxidant capacity was also documented by Afsar et al. (16).In the DPPH experiment, the plant's methanolic extract demonstrated potent reducing actions. Furthermore, the extract's ability to scavenge radicals became increasingly apparent as its concentration rose.¹⁶

5.4 Anti-Asthmatic:

Boswellia is a well-known and versatile medication with a long history of usage, particularly in relation to respiratory disorders . It has been utilised in the form of steam inhalations, baths, and massages to treat a range of conditions, including cough, catarrh, bronchitis, and asthma. The higher terpenoids found in frankincense, known as BAs, play a pivotal role in inhibiting leukotriene biosynthesis. Consequently, they contribute to the reduction and prevention of inflammation in numerous chronic inflammatory diseases, including asthma. The alcohol extract of Salai guggul (AESG) has been shown in several trials to provide anti-asthmatic effects in people with a protracted history of asthma. This effect is attributed to the stimulation of MAPK, mobilization of intracellular Ca2+, and the inhibition of leukotriene biosynthesis¹⁷

5.5 Anti-Bacterial:

Salmonella typhimurium, Salmonella typhi, Proteus vulgaris, Enterobacter aerogenes, Staphylococcus aureus, Klebsiella pneumonia, and Salmonella typhimurium are some of the bacterial strains that Bhatuda et al. (18) evaluated for antibacterial properties of Boswellia serrata. The results of their experiment showed that the plant's methanolic extract had strong antibacterial activity.^18,19,20

5.6 Analgesic and Psychopharmacological:

In many conventional medical systems, frankincense is used to relieve arthritic and muscle pain. Bishnoi et al.¹⁹ utilised the tail flick and acetic acid-induced writhing procedures to investigate the analgesic efficacy of AKBA at different dose levels in mice. In writhing caused by acetic, they saw a dose-dependent increase in the antinociceptive action of AKBA, however in the tail flick approach, 100 mg and 200 mg of AKBA responded similarly Demonstrated superior performance than nimesulide, the positive control .Menon and Kar reported that B. serrata demonstrated significant sedative and analgesic effects.²¹Additionally, following Boswellia administration, they noted a marked decrease in spontaneous motor activity.

Fig.No.3 : Pharmacological effects of Boswellia serrata

6. Boswellia serrata in Herbal Medicines:

Herbal medicine sales and distribution are significantly rising in the worldwide phytomedicine market, in addition to the enforcement of control and regulatory measures.^22,23 Standardisation, quality control, and supervision of the manufacturing of herbal medicines are major problems that impact both developed and developing countries globally.^24,25

Boswellia serrata Roxb a member of the Burseraceae family, is among the notable medicinal plants. Extensive literature research underscores its potential as a promising plant. Commonly referred to as gum resin, it possesses significant medicinal applications. In Sanskrit, it is also known as 'Gajabhakshya,' alluding to its use as a dietary herb by elephants." Boswellia serrata holds significant importance in Ayurveda, where it is recognized by various names, including Shallaki, Susravaa, Gajabhakshyaa, Salai, and Gumkunduru.²⁶ This herb is essential to the treatment of many illnesses in Ayurvedic medicine.It is particularly effective in pacifying the Kapha and Pitta doshas within the body, and it is primarily employed to address diseases associated with these doshas. The anti-inflammatory and anti-arthritic qualities of Boswellia serrata have been mentioned in ancient Ayurvedic writings including the Sushruta Samhita and Charaksamhita.²⁷

Indigenous communities maintain a profound connection with their natural environment, possessing in-depth knowledge of the diverse plant resources in their surroundings. They leverage these natural resources creatively to extract maximum benefits. For instance, Many traditional cultures use the herb Boswellia serrata, which is well-known for its medicinal qualities, to cure a variety of illnesses. Some tribes in Sonaghati, Uttar Pradesh, use a bark decoction of Boswellia serrata to treat stomach ache.

Moreover, a concoction of Leea crispa root and Boswellia serrata bark is a popular remedy for snakebite. Wounds can also be treated using an ointment consisting of gum Boswellia serrata, according to reports.²⁸

The plant's dried resin acts as a natural mosquito and germ repellant in Chinnar Wildlife Sanctuary.²⁹ Andrographis paniculata, Boswellia serrata leaves, and goat urine are used in formulations to treat edoema in Cuddapah District, Andhra Pradesh. In²⁹. A blend of Caesalpinia crista fruit and seeds and Boswellia serrata resin is historically used in Dharapuram Taluk, Tamil Nadu, to cure hydrocoele.³⁰

Boswellia serrata resin is used to treat rheumatic and joint discomfort in Sonbhadra, Uttar Pradesh. The resin is utilised not only as a hair tonic but also as a wound cure³¹. In Southern Rajasthan, gum resin is used to cure impotence in men.³² Boswellia serrata bark, resin, and leaves are used to treat colds, diarrhoea, dysentery, and wounds in Sonebhadra District, Uttar Pradesh.³³ In Eastern Uttar Pradesh, the plant is recognised for its blood-purifying, antipyretic, antidiabetic, anti-leukoderma, and anti-rheumatoid arthritis properties.³⁴ It's a headache treatment as well.³⁵

Furthermore, a mixture of gum resin and long pepper in mustard oil functions as a hair tonic to encourage the growth of new hair.³⁶

PHARMACOLOGY OF BOSWELLIA SERRATA AGAINST ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES:

The primary constituent of Boswellia serrata is boswellic acid, which has potent pharmacological effects in the treatment of inflammatory ailments, such as rheumatoid arthritis, asthma, persistent bronchitis and persistent inflammatory bowel disorders (such as Crohn's disease and ulcerative colitis). β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid (KBA), and acetyl-11-keto-β-boswellic acid are the four primary pentacyclic triterpenic acids present in the resinous portion of Boswellia serrata. .The pro-inflammatory enzymes are inhibited by these substances.³⁷

According to studies, the main physiologically active ingredient in the plant is 3-O-acetyl-11-keto-beta-boswellic acid (AKBA). It prevents 5-lipoxygenase from acting, which is an enzyme involved in the chain of events that causes inflammation.³⁸

Rats with adjuvant arthritis caused by carrageen-induced paw edoema are used to assess anti-inflammatory and anti-arthritic properties. When given orally (p.o.), DAESG therapy reduced the amount of carrageen in rat hind paw oedema by 39.75% and 65-73%. ranges of 50-200mg per kg-1 and 50-100mg per kg for interaperitoneal (i.p.) administration, in contrast to the 47% inhibition seen with phenylbutazone (50mg/kg-1 p.o.)³⁹ Rats that had had their adrenal glands removed also showed a strong anti-inflammatory impact. In the research on anti-arthritis, salai guggal demonstrated 34% and 49% suppression of paw swelling with 50 and 100mg per kg (p.o.) dosages in rats with mycobacterial adjuvant-induced polyarthritis. correspondingly in relation to the controls. Phenyl butazone showed 26% and 60% inhibition at 50 and 100mg per kg (p.o.), respectively.⁴⁰

Both KBA and AKBA have long retention periods, but they also have low GIT absorption since they are highly lipophilic drugs. Following the injection, human plasma had traces of both AKBA and KBA, according to preliminary pharmacokinetic investigations. Even though no metabolites of AKBA could be found, studies conducted in vitro and in vivo demonstrated that the metabolic profiles of KBA in rat liver and plasma were comparable. This indicates that further administration step implementation is needed to increase AKBA's bioavailability.⁴¹ According to another study, accumulation inside the enterocytes, CYP3A4-mediated intestinal metabolism, saturable kinetics, and gastrointestinal instability were the primary permeability-related obstacles to KBA's oral bioavailability.⁴²

BOSWELLIC ACID IMPLICATED IN DIFFERENT PHASES OF HUMAN CLINICAL TRIALS:

Studies conducted in preclinical and clinical settings have demonstrated the extraordinary potential of BA against a variety of chronic illnesses, as was previously indicated. In a double-blind, placebo-controlled human trial, participants discovered that an oral version of boswellin helped those with osteoarthritis feel less achy and less inflammatory.⁴³ It included AKBA and BBA. Additionally, individuals with osteoarthritis reported better physical performance and less pain after taking a new BSE called 5-Loxin, which contained 30% AKBA. Reduced levels of pro-inflammatory modulators and cartilage enzymatic degradation may have been the cause of this improvement due to the BSE's safe and efficient management of inflammatory responses.⁴⁴

Additionally, individuals with osteoarthritis responded favourably to a comparative, randomised, double-blind, placebo-controlled research that looked at the safety and effectiveness of curcumin in conjunction with BA.⁴⁵ BA and methylsulfonylmethane (MSM) together also showed promising results in the treatment of knee arthritis.⁴⁶ However, Notarnicola et al. showed that in instances with gonarthrosis, this combination had no impact⁴⁷, Further research revealed that utilising the lecithin-based delivery form of B. serrata, referred to as Casperome®, resulted in a noteworthy and safe decrease in the indications and symptoms experienced by irritable bowel syndrome sufferers.⁴⁸ A double-blind, placebo-controlled research found that patients with bronchial asthma had significant improvement after consuming BSE with high concentrations of BAs. symptoms such as attack volume, dyspnea, and rhonchi; increases in FEV subset1, FVC, and PEFR; and a reduction in the eosinophilic.⁴⁹

In addition, a prospective, randomised, placebo-controlled, double-blind pilot study showed that BSE treatment dramatically reduced cerebral edoema in individuals who had received radiation therapy for brain tumours.⁵⁰ Additionally, a clinical research carried out by Gerhardt and colleagues to contrast the
H15 While taking into account a benefit-risk analysis, a BSE that combines mesalazine with efficacy and safety for treating active Crohn's disease was determined to have a better impact.⁵¹

Furthermore, a novel BA formulation including lecithin, a B. serrata resin extract, and Bosexil(®), INCI (International Nomenclature of Cosmetic Ingredients), was demonstrated to be a viable therapy choice for psoriasis and erythematous eczema sufferers.⁵²Additionally, a well-tolerated and secure treatment method for photoaged skin was demonstrated by the topical administration of a cream containing 0.5% BA.⁵³ Consequently, these trials clearly show that BA is effective, safe, and well-tolerated. indicates that there is a good chance that it can be used to treat a number of chronic human illnesses.⁵⁴

Potential side effects of Boswellia serrata⁵⁵

Frankincense, or Boswellia, is harmless and has not been proven to cause any serious negative effects. The minimal side effects that are possible include^56-63

1. Nausea

2. Abdominal pain

3. Heartburn

4. Itching

The toxicity of boswellia resin is quite low. The US Food and Drug Administration (USFDA) has approved its usage as a food additive and it is listed among safe compounds. In dietary levels, it's even safe throughout pregnancy and breastfeeding; but, the safety of therapeutic dosages (found in supplements) hasn't been studied. Consult your physician before to using supplements.^64-69

In rats, a repeated dose oral toxicity study (90 days) of Boswellia serrata revealed that the herb was generally safe at doses between 500 and 1,000 mg/kg. No detrimental effects on health were noted. Boswellia resin and AKBA demonstrated moderate to low skin toxicity in a standard toxicology study.^70,71

CONCLUSION:

Boswellia serrata is a plant of Indian origin named sallaki in Ayurveda Boswellia serrata has found mention in numerous Ayurvedic texts, attesting to its historical significance. There are several uses for the gum resin that comes from Boswellia serrata, including both medicinal and non-medical ones . The present review article provides a comprehensive exploration of every facet of this plant, including its, phytochemistry, pharmacological actions utilization in traditional medicinal systems, and its therapeutic importance. Pharmacological properties of this Boswellia serrata plant include anti-inflammatory and anti-arthritis, anticancer or antitumor, Antioxidant, antibacterial, anti-asthmatic, and analgesic properties. Furthermore, it is crucial to address the issue of rapid overexploitation of this species. Urgent measures are required to establish preventive management practices to protect Boswellia serrata. To keep this species from going extinct, it is essential to guarantee its sustainable supply.

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Received on 10.05.2024 Modified on 21.06.2024

Research J. Science and Tech. 2024; 16(3):255-264.

DOI: 10.52711/2349-2988.2024.00036