1. Introduction:

Across centuries, traditional medicine practitioners worldwide have utilized extracts derived from Boswellia trees (Burseraceae family) to address various medical conditions¹. This remarkable genus encompasses approximately 25 distinct species, with several notable members including Boswellia serrata, sacra, carterii, papyrifera, neglecta, rivae, frereana, and ovalifoliolata. In India, the species grows abundantly across the dry, elevated regions of multiple states - from Rajasthan and Gujarat to Maharashtra, Madhya Pradesh, Bihar, and Orissa, extending into sections of the Western Himalayas². The bark of B. serrata yields a valuable oleo-gum-resin through exudation, which, after drying, forms whitish-yellow tears or lumps³. This substance, commonly identified as Indian Frankincense or Salai guggal, or Indian olibanum⁴.

India's traditional healing system, named Ayurvedic medicine, has long employed this gum to treat inflammatory conditions affecting multiple body systems, including the skin, eyes, gums, gastrointestinal tract, and respiratory system - particularly addressing ailments like asthma, bronchitis, and laryngitis. The composition of this oleo-gum-resin combines essential oils (containing mono-, di-, and sesquiterpenes, along with phenolic compounds and serratol, diterpene alcohol), gum (rich in pentose and hexose sugars plus various enzymes), and resin. Notably, all Boswellia species contain boswellic acid, a pentacyclic triterpene acid, as their primary bioactive component⁵.

Extensive research, documented through numerous studies and reviews, demonstrates the therapeutic potential of boswellic acids (BAs) in managing chronic inflammatory conditions. These include ulcerative colitis, rheumatoid arthritis, Crohn's disease, and bronchial asthma⁶. Additionally, research indicates beneficial effects on mental health conditions and brain tumors. Among the various BAs derivatives, two compounds stand out for their potent anti-inflammatory properties: acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-beta-boswellic acid (KBA)⁷. Figure 1 illustrates the different benefits and therapeutic advantages of BA and its derivatives.

Figure 1. Therapeutic benefits of BA and their derivatives.

2. Pharacokinetics properties of Boswellic acids:

The absorption and distribution of KBA (11-Keto β-Boswellic acid) and AKBA (3-O-acetyl-11-keto-β-Boswellic acid) present an interesting pharmacological challenge. These compounds are highly lipophilic, meaning they readily dissolve in fats but poorly in water.

Researchers have developed several innovative approaches to enhance the bioavailability of these compounds. One breakthrough came with the use of lecithin-based delivery systems. Lecithin, a natural phospholipid, acts as a bridge between fat-soluble and water-soluble environments. This delivery method not only improves absorption but also makes the absorption more consistent across different patients⁸.

Researchers compared the bioavailability of Casperome™, a soy lecithin–based formulation of Boswellia serrata extract, with its non-formulated counterpart. Distribution of six boswellic acids, as provided in Figure 2 (KBA, AKBA, βBA, AβBA, αBA, AαBA), was evaluated in plasma and tissues, including brain, muscle, eye, liver, and kidney, using AUC analysis. Casperome™ significantly increased plasma levels after oral administration, with KBA rising to sevenfold and βBA threefold. Brain concentrations of KBA and AKBA increased ~35-fold, while βBA tripled. In less vascularized tissues such as the eye, BA levels were up to 17-fold higher. These results demonstrate improved systemic absorption and tissue distribution of boswellic acids with Casperome™⁹.

Figure 2. Major therapeutically active derivatives of BAs.

A single-dose crossover clinical trial compared the pharmacokinetics and pharmacodynamics of two Boswellia serrata nutraceuticals: a native dry extract (Biotikon® BS-85) and a micellar formulation (Boswellia-Loges®). Twenty healthy volunteers received an 800 mg oral dose of each formulation. Plasma levels of eight boswellic and lupeolic acids were analyzed by HPLC-MS/MS over 48 hours. The micellar formulation significantly increased C_max and AUC and reduced T_max, with AKBA bioavailability rising by 1,720–4,571%. However, despite better absorption, it showed weaker anti-inflammatory effects; the native extract more effectively reduced IL-1β and IL-6, while both formulations similarly inhibited TNF-α and NF-κB activity¹⁰.

Understanding these pharmacokinetic properties has important implications for therapeutic use.

3. Mechanisms of action:

A key anti-inflammatory mechanism of boswellic acids (BAs) is inhibition of 5-lipoxygenase (5-LO), an enzyme in neutrophils that converts arachidonic acid into inflammatory mediators such as 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotrienes. These mediators promote inflammation by causing vasoconstriction, airway narrowing, increased tissue permeability, and recruitment of inflammatory cells. BAs act as non-redox inhibitors, selectively blocking 5-LO activity without affecting related enzymes like cyclo-oxygenase or 12-lipoxygenase. This targeted inhibition reduces leukotriene production and inflammation while minimizing interference with other cellular pathways ¹¹.

Boswellic acids (BAs) exert therapeutic effects through multiple mechanisms. One involves inhibition of leukocyte elastase, an enzyme that can damage lung tissue when overactive by reducing elasticity, narrowing airways, and disrupting mucus balance. By limiting elastase activity, BAs may help prevent conditions such as emphysema. Additionally, BAs modulate immune responses by inhibiting C2 convertase in the complement system and influence cellular signaling through MAPK (p38) pathways, with effects varying across cell types¹².

Boswellic acids (BAs) modulate immune responses by inhibiting C2 convertase, a key enzyme of the complement system involved in antibody-mediated pathogen clearance¹³. They also influence MAPK signaling, particularly the p38 pathway, with effects that may vary across cell types, either stimulating or inhibiting the pathway¹⁴.

4. Pharmacotherapeutic actions of Boswellic acids:

4.1. Anticancer or antitumor activity:

The scientific community has extensively documented the anti-cancer properties of β-BA and its derivatives, which form the primary components of Boswellin. These compounds work through several mechanisms: they inhibit crucial enzymes called topoisomerases I and IIa, effectively halting cancer cell growth and multiplication. Advanced mass spectrometry studies have revealed another fascinating aspect - β-BAs can actually interfere with protein production by interacting with ribosomal components, thereby influencing cancer progression¹⁵.

Studies suggest β-boswellic acid (β-BA) may help prevent breast precancerous lesions. In rat models, β-BA significantly reduced lesion formation, indicating prophylactic potential. Experiments with MCF-10AT cells showed that β-BA inhibited proliferation and induced cell death while largely sparing normal MCF-10A cells. Mechanistically, β-BA disrupts cellular metabolism, particularly glycolysis. KEGG pathway analysis and experimental validation revealed reduced glycolysis and ATP production. Molecular docking further indicated interaction with glucose transporter-1 (GLUT1); overexpression of GLUT1 reversed β-BA effects, restoring glycolysis and cell proliferation, highlighting GLUT1’s key role in its mechanism¹⁶.

Studies on acetyl-11-keto-β-boswellic acid (AKBA) show significant cytotoxic effects against MCF-7 breast cancer cells. In vitro results demonstrate a dose-dependent reduction in cell viability and colony-forming ability. Mechanistically, AKBA increases reactive oxygen species (ROS) generation, inducing oxidative stress–mediated cytotoxicity. It also activates caspase-8 and caspase-9, indicating involvement of both extrinsic and intrinsic apoptotic pathways. Flow cytometry further reveals G1 phase cell cycle arrest, leading to reduced proliferation and programmed cell death. Comparative studies indicate that AKBA and ABA exhibit stronger anti-cancer activity against MCF-7 cells than β-boswellic acid (BA)¹⁷.

Further, various forms of boswellic acid demonstrated impressive abilities to prevent DNA, RNA, and protein synthesis in these leukemia cells, with the effects on DNA being permanent¹⁸.

In the context of lung cancer treatment, researchers have made an exciting discovery about combining traditional chemotherapy with natural compounds. While cisplatin remains a crucial treatment for non-small cell lung cancer (NSCLC), drug resistance often limits its effectiveness. However, when combined with AKBA, researchers observed enhanced treatment outcomes. This combination works by stopping cell division at the G0/G1 phase, promoting cell death, and reducing cellular survival mechanisms through p21-dependent signaling [19,20].

Studies focusing on Taxol-resistant ovarian cancer cells reveal that AKBA not only stops cancer cell growth but also prevents their movement and invasion. The compound achieves this by increasing the concentration of certain chemicals within cells and blocking resistance-related proteins like P-glycoprotein, LRP, BCRP, and MRP²¹.

Studies in brain cancer research show that acetyl-11-keto-β-boswellic acid (AKBA) exhibits strong anti-glioma activity. Glioma migration and metastasis are associated with increased expression of transcription factors TWIST1 and FOXM1. In experiments with U87MG glioblastoma cells, treatment with 50 µM AKBA significantly reduced cell migration, as shown by wound healing assays. Real-time PCR analysis further revealed marked downregulation of TWIST1 and FOXM1 gene expression. These findings suggest that AKBA suppresses glioblastoma cell motility by targeting key transcription factors involved in tumor progression, highlighting its potential as a therapeutic candidate for glioma treatment²².

This comprehensive body of research underscores the significant potential of BAs in cancer treatment, particularly when used in combination with existing therapies.

4.2. Boswellic acids as Anti-COVID-19 and antiviral agents:

One significant study examined how certain plant-derived compounds interact with the SARS-CoV-2 envelope (E) protein, which plays a crucial role in how the virus functions²³. Through molecular docking studies, researchers discovered that β-boswellic acid forms strong connections with this viral protein. The compound showed impressive binding strength, measuring -9.1 kcal/mol in binding energy, suggesting it could effectively interfere with the virus's activities. When tested in laboratory conditions, these compounds demonstrated the ability to disrupt about 90% of the E protein's structure²⁴.

Clinical trials with COVID-19 patients revealed promising results when treated with frankincense extract. Patients showed improved oxygen levels and potentially shorter hospital stays. Importantly, the treatment appeared to help regulate the immune response by reducing levels of IL-6, an inflammatory molecule that often causes problems in severe COVID-19 cases. The treatment showed remarkable effectiveness, reducing the number of positive tests by 44%²⁵. The compounds work through several mechanisms to fight viruses. Pentacyclic triterpenoids, a class of compounds found in frankincense, can prevent viruses from entering cells by interacting with a specific part of viral envelopes called the HR2 domain. This mechanism works against various viruses, including Ebola, HIV, and influenza A²⁶.

Clinical studies highlight the potential of frankincense extract in managing respiratory viral infections. In a trial involving patients aged 65–80 years with dementia, daily administration of 1200 mg frankincense extract significantly reduced inflammatory markers. Frankincense extracts and boswellic acids (BAs) have shown activity against several respiratory viruses, including SARS-CoV-1, SARS-CoV-2, MERS, influenza (H1N1, H5N1, H7N1), rhinovirus, and RSV. Laboratory studies demonstrated reduced viral plaque formation in treated cells, indicating inhibited viral replication. Various BAs, such as A-α-BA, A-β-BA, and β-BA, also protected cells from coronavirus-induced damage^27,28.

This research suggests that these natural compounds might offer a valuable tool in our arsenal against viral infections, particularly through their ability to reduce inflammation and directly interfere with viral replication.

4.3. Anti-inflammatory and anti-arthritic activity:

The effectiveness of these compounds has been demonstrated in numerous clinical trials. For example, when researchers tested Boswellia serrata extract in patients with inflammatory conditions, an impressive 88% of participants showed significant improvement, ranging from fair to excellent results. It is particularly significant that these advantages were attained without the adverse effects often linked to traditional anti-inflammatory drugs²⁹. The researchers developed an extract containing 10% AKBA and compared it to a standard 2% formulation. The results were remarkable - the 10% version showed over 110 times better absorption into the bloodstream. When combined with a common arthritis medication called methotrexate, this enhanced AKBA extract not only improved the treatment's effectiveness but also helped protect the liver from potential medication-related damage³⁰. In one compelling study, researchers reported that Boswellia extract significantly reduced inflammation in cases of ulcerative colitis, while also protecting against oxidative stress - demonstrating its dual anti-inflammatory and antioxidant properties³¹.

BAs have been tested in clinical studies to see if they can help reduce inflammation. A prominent randomized, double-blind, three-arm parallel trial including 201 individuals showed that people with osteoarthritis (OA) had a lot of improvements in their symptoms, such as better physical performance, less severe disease, and lower WOMAC scores. These results add to the evidence that BAs can help reduce inflammation, which shows that they could be used to treat arthritis³².

4.4. Boswellic acids as Antidiabetic agents:

BAs have garnered attention for their potential antidiabetic properties. Research indicates that these acids can modulate blood glucose levels and enhance insulin sensitivity^27,33.

A recent meta-analysis examining five studies with 287 patients demonstrated that Boswellia supplementation significantly improves several key markers of diabetes management. The analysis revealed reductions in glycated hemoglobin (HbA1C), total cholesterol, triglycerides, and LDL levels. While fasting blood glucose showed a downward trend, it didn't reach statistical significance, and HDL levels remained unchanged³⁴.

The antidiabetic effects of β-boswellic acid (β-BA) and 11-keto-β-boswellic acid (β-KBA) have been investigated by Khan and colleagues (Figure 3). In 21-day animal studies, both compounds normalized body weight, reduced excessive water intake, lowered blood glucose, and improved lipid profiles by decreasing total cholesterol, triglycerides, and LDL-C while increasing HDL-C. Inverse docking identified dipeptidyl peptidase-4 (DPP-4) as a potential molecular target, and subsequent in vitro studies confirmed that β-BA and β-KBA inhibit DPP-4 activity. These findings indicate their potential as therapeutic agents for diabetes management³⁵.

Figure 3. (A) The binding potential of β-BA and β-KBA with the selected drug targets, as determined by docking scores. A higher binding affinity is represented in green, while lower to minimal binding potential is indicated by a gradient from orange to red. (B) The binding interactions of β-BA and β-KBA within the active site of DPP-4 are illustrated as a golden ribbon. Image reproduced from³⁵ under the terms of the Creative Commons Attribution 4.0 International License..

A study on streptozotocin-induced type II diabetic rats showed significant antihyperglycemic effects of Boswellia sacra oleo-gum resin extracts (Figure 4). The ethanolic extract, containing the highest level of pentacyclic triterpenic acids (391.52 mg/g), was most effective. A dose of 200 mg/kg/day reduced blood glucose more effectively than 400 mg/kg/day. In a 180-min OGTT, this dose improved glucose tolerance, outperforming metformin and approaching normal control levels. Treated rats also showed weight gain, increased insulin, reduced IL-2 and IL-8, and decreased oxidative stress through higher SOD and GSH activity. Histological analysis indicated protective effects on pancreatic and liver tissues³⁶.

Figure 4. (i) Analysis of pentacyclic triterpenic acids (PTAs) extracted from B. sacra. (ii) Histological examination of rat pancreas tissues (H&E staining, 400×). Panel P1 shows normal pancreatic architecture with intact acinar cells. P2 shows STZ-induced diabetic damage with degeneration and necrosis of islet cells, shrunken islets, and damaged acini. P3–P7 depict pancreatic regeneration in rats treated with B. sacra extracts (200 or 400 mg/kg), showing restoration of islet structure and cellular recovery. P8 shows the metformin-treated group with mild inflammatory infiltration and acinar hyperplasia. Image reproduced from³⁶ under CC BY 4.0.

A double-blind, randomized, placebo-controlled clinical trial evaluated the effects of Boswellia serrata gum resin on glucose and lipid levels in type 2 diabetic patients. Fifty-six participants received either 250 mg Boswellia or a placebo twice daily for eight weeks alongside standard antidiabetic therapy. Although the Boswellia group showed reductions in fasting blood glucose, glycosylated hemoglobin, and lipid levels, no significant differences were observed compared with the placebo group. The study concluded that 500 mg/day Boswellia serrata for eight weeks did not provide additional improvement in glucose or lipid profiles beyond standard treatment³⁷.

4.5. Immunomodulatory activity:

Among the six different BAs, AKBA (Acetyl-11-keto-β-boswellic acid) stands out as particularly potent in inhibiting 5-lipoxygenase (5-LO), an enzyme involved in inflammation. This helps explain why AKBA is often considered the most active compound in Boswellia extracts³⁸.

In terms of cellular immunity, BAs influence lymphocyte activity - again in a dose-dependent manner. At lower concentrations, they promote lymphocyte proliferation, while higher concentrations inhibit it. They also enhance macrophage phagocytosis (the ability of immune cells to engulf and destroy foreign particles) and affect cytokine production, which are important signaling molecules in the immune system³⁹.

Researchers evaluated AKBA (acetyl-11-keto-β-boswellic acid) content and in vitro antioxidant activity in several commercial Boswellia serrata preparations. Significant variation in AKBA levels was observed, ranging from 3.83 ± 0.10% to 0.03 ± 0.004%, with one extract showing no detectable AKBA. The sample with the highest AKBA also exhibited the strongest antioxidant activity and phenolic content. Additionally, the extracts influenced both regulatory and effector T-cell populations, suggesting potential roles of Boswellia serrata in modulating immune dysfunction, oxidative stress, and inflammation⁴⁰.

These findings collectively demonstrate that Boswellia compounds act as sophisticated immunomodulators, capable of both enhancing and suppressing different aspects of immune function depending on concentration and specific context..

4.6. Hepatoprotective activity:

Preclinical investigations have highlighted the hepatoprotective properties of Boswellia serrata (BS) gum resin against various models of liver toxicity, primarily through its antioxidant, anti-inflammatory, and anti-fibrotic effects⁴¹.

A study investigated the hepatoprotective effects of Boswellia serrata (BS) gum resin against carbon tetrachloride (CCl₄)-induced liver injury in rats. Treatment significantly reduced elevated liver enzymes ALT, AST, and LDH, indicating protection against hepatocyte damage. The protective effect was linked to enhanced hepatic antioxidant activity, increased catalase, reduced lipid peroxidation, and decreased expression of inflammatory markers, including TGF-β, NF-κB, TNF-α, and IL-6. By modulating oxidative stress and inflammatory pathways, BS gum resin helps preserve liver structure and function under toxic conditions⁴².

Zaitone and colleagues investigated the effects of boswellic acids (BAs) on non-alcoholic fatty liver disease (NAFLD) using a high-fat diet–induced rat model. Treatment with BAs (125 and 250 mg/kg) improved insulin sensitivity, reduced liver damage markers, and lowered inflammatory cytokines TNF-α and IL-6, along with decreased iNOS expression. At 250 mg/kg, BAs also enhanced fat metabolism by increasing expression of thermogenesis-related proteins, including mitochondrial uncoupling protein-1 (UCP-1) and carnitine palmitoyl transferase-1 (CPT-1) in white adipose tissue. These findings suggest BAs may improve metabolic function and reduce inflammation in NAFLD⁴³.

Kumar et al. carried out a second study to assess β-AKBA's preventive ability against benzo(a)pyrene-induced liver injury. Their results show that the β-AKBA injection greatly lowered elevated liver enzymes and helped to restore liver tissue structure disturbed by benzo(a)pyrene. Conversely, it did not cause any alterations in the signs of oxidative stress present in the liver⁴⁴.

In their study, Thabet and colleagues investigated the hepatoprotective properties of Boswellia serrata extract, which is composed of 65% BAs. The findings of the study indicate that the administration of the extract resulted in significant reductions in the levels of AST and ALT in the blood, as well as decreases in the levels of hepatic MDA, IL-6, and TNF-α. Following the implementation of these adjustments, it was discovered that the levels of glutathione (GSH) had been restored⁴⁵.

This multifaceted approach to liver protection makes Boswellia particularly interesting as a potential therapeutic agent for various liver conditions.

4.7. Anti-asthmatic activity:

The researchers discovered that BA achieves these effects by blocking two important proteins: pSTAT6 and GATA3. By preventing this development, BAs help stop the asthmatic response before it can fully develop⁴⁶.

In a BALB/cJ mouse model of allergic asthma, Suther and colleagues evaluated the anti-asthmatic effects of β-AKBA. Treatment reduced lung inflammation, bronchial smooth muscle remodeling, and mucus production, while improving airway function by decreasing airway hyperresponsiveness and bronchoconstriction in methacholine challenge tests. Levels of inflammatory cytokines IL-4 and IL-5 in bronchoalveolar lavage fluid, along with leukocyte and eosinophil counts, were also reduced. The study suggested that β-AKBA may partly act through gut microbiome modulation, particularly by increasing Bifidobacterium pseudolongum, which helps reduce lower airway inflammation⁴⁷.

These findings help explain the long-standing use of Boswellia in treating respiratory disorders. Its multi-target actions, including anti-inflammatory effects, immune modulation, and protection of tissue structure, make it useful for complex respiratory conditions involving multiple pathological processes.

4.8. Anti-microbial activity:

Throughout evolutionary history, plants have developed Notably, Bas derived from Boswellia sacra and Boswellia serrata have been traditionally utilized to treat microbial and fungal infections. Studies have demonstrated that monoterpenoids present in B. sacra essential oil exhibit antibacterial activity against Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus. Additionally, BAs have been shown to significantly inhibit the growth of fungi such as Malassezia furfur and Candida albicans⁴⁸.

Recent studies by Jaros and colleagues examined the antimicrobial activity of boswellic acids (BAs) against bacterial growth and biofilm formation. BAs showed synergistic effects with conventional antibiotics, enhancing antimicrobial efficacy. Notably, the combination of erythromycin (0.2 mg/L) and boswellic acid (16 mg/L) significantly inhibited Enterococcus faecalis ATCC 29212. Further studies on oral pathogens revealed that AKBA exhibited broad-spectrum antimicrobial activity with MIC values of 2–4 mg/mL. It was particularly effective against Streptococcus mutans, inhibiting resistant strain development, preventing biofilm formation, and disrupting existing biofilms, suggesting potential use in oral hygiene products such as mouthwashes⁴⁹.

Attallah and colleagues further demonstrated strong antibacterial and antibiofilm activity against Porphyromonas gingivalis, a key periodontal pathogen. Chemical analysis identified 49 compounds, including trans-nerolidyl formate and cycloartenol acetate, contributing to this activity⁵⁰. Additional studies also confirmed the effectiveness of boswellic acids (BAs) against a wide range of gram-positive and gram-negative bacteria.

4.9. Analgesic and psychopharmacological activity:

of frankincense. Studies on Boswellia elongata methanolic leaf extract showed that oral doses of 50 and 100 mg/kg significantly reduced edema in animal models, indicating peripheral analgesic and anti-inflammatory activity, though no central analgesic effect was observed⁵¹.

In another study, Bishnoi and colleagues evaluated AKBA using mouse pain models. AKBA showed dose-dependent analgesic effects in the writhing test, while the tail-flick test suggested a ceiling effect at 100 mg. Notably, AKBA exhibited stronger analgesic activity than nimesulide, a standard anti-inflammatory drug⁵².

Harrasi and colleagues took a different approach, conducting a detailed analysis of Boswellia sacra, a species traditionally used for pain management in Omani medicine. They evaluated pain response using two distinct models: the acetic acid-induced writhing test and the formalin-induced pain model, providing complementary perspectives on the compound's pain-relieving capabilities. Their most striking finding emerged from the polar sub-fractions (specifically those extracted with 2% and 4% methanol), which demonstrated remarkable analgesic potency - approximately twice that of aspirin, their positive control⁵³.

Based on these collective findings, the researchers proposed that Boswellia compounds achieve their pain-relieving effects through a sophisticated dual mechanism, operating at both peripheral and central levels in the nervous system.

4.10. Neuroprotective effects:

Neurodegenerative conditions like Alzheimer's disease progress largely due to neuroinflammation - a chronic inflammatory state in the brain that damages nerve cells over time^54,55. Animal studies show that frankincense (olibanum) can protect against experimentally induced Alzheimer’s disease by reducing oxidative stress, suppressing inflammation, and inhibiting acetylcholinesterase, thereby preserving memory-related neurotransmitters⁵⁶.

A study by Mohamed and colleagues further demonstrated that AKBA (250 mg/kg for three weeks) reduced tau protein levels, a key factor in Alzheimer’s pathology, while improving glucose transport, neurotransmitter levels (dopamine and acetylcholine), and mitochondrial energy production, highlighting its potential role in neuroprotection⁵⁷.

Recent studies have explored combination strategies involving boswellic acids (BAs). Miao and colleagues reported that BAs combined with myrrh sesquiterpenes reduced neuroinflammation in brain immune cells by modulating multiple signaling pathways; network analysis identified four key compounds targeting 31 proteins involved in neuroinflammatory processes⁵⁸.

Similarly, Sayed and Sayed showed that AKBA combined with COX-2 and 5-LO inhibitors effectively protected against cognitive impairment in mice through anti-inflammatory and anti-glutamatergic mechanisms⁵⁹.

BAs also exhibit a favorable safety profile, with an LD₅₀ > 2 g/kg and only mild side effects such as minor gastrointestinal discomfort or occasional skin reactions⁶⁰.

This comprehensive body of research suggests that BAs could potentially serve as valuable therapeutic agents for various neurodegenerative conditions, working through multiple protective mechanisms while maintaining a favorable safety profile.

4.11. BW in Ocular diseases:

Yang and colleagues investigated the protective effects of AKBA against age-related cataracts. Their study showed that AKBA improves cell survival under stress and reduces the accumulation of reactive oxygen species (ROS). It also inhibits apoptosis by decreasing pro-apoptotic proteins caspase-3 and Bax while increasing the anti-apoptotic protein Bcl-2. Importantly, AKBA activates the Keap1/Nrf2/HO-1 signaling pathway, a key cellular defense mechanism against oxidative stress. By interacting with Keap1, AKBA enables Nrf2 to translocate to the nucleus and induce antioxidant gene expression, thereby protecting lens cells from oxidative damage⁶¹.

BA is also utilized alongside other photoactive agents for the treatment of ocular diseases. A recent study aimed to evaluate the morphological and functional impacts of orally administered Curcuma longa and Boswellia serrata on individuals with treatment-naïve non-proliferative diabetic retinopathy (DR) and diabetic macular edema (DME). The findings suggest that oral administration of Curcuma longa and Boswellia serrata may safeguard baseline CMT and BCVA metrics in individuals with non-proliferative diabetic retinopathy and treatment-naïve diabetic macular edema. The concurrent use of these agents could be considered a supplementary therapy for DME patients receiving intravitreal injections⁶².

Lulli and colleagues investigated the role of AKBA in inhibiting abnormal retinal blood vessel formation. The study showed that AKBA increases SHP-1 activity, a regulator that suppresses cell signaling, while reducing STAT3 activity, which promotes angiogenesis. It also lowers VEGF levels and blocks its receptor VEGFR-2, key drivers of new blood vessel growth. Experiments using human retinal endothelial cells further confirmed that AKBA inhibits cell proliferation, migration, and tube formation, critical steps in angiogenesis⁶³. These findings suggest AKBA may offer a natural therapeutic approach for retinal vascular disorders.

Apart from the above-explained pharmacological activities, Table 1 presents an overview of derivatives of BAs and their pharmacological action

5. CONCLUSION

Boswellic acids (BAs) have gained significant attention due to their diverse therapeutic applications supported by preclinical and clinical evidence. Their strong anti-inflammatory activity makes them effective in managing chronic inflammatory disorders, while their anticancer potential highlights their value as an adjuvant therapy. Additionally, BAs exhibit neuroprotective, hepatoprotective, and immunomodulatory effects, suggesting broader biomedical applications. However, variability in resin composition and poor bioavailability require further research on optimized formulations and targeted delivery systems. Future work should prioritize large-scale clinical trials to establish standardized dosing and long-term safety. Incorporating BAs into modern pharmacological formulations could help bridge traditional medicine with contemporary therapeutics and advance their role in evidence-based medicine.

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Received on 03.03.2025 Revised on 28.06.2025

Accepted on 25.09.2025 Published on 03.04.2026

Available online from April 06, 2026

Research J. Pharmacy and Technology. 2026;19(4):1875-1884.

DOI: 10.52711/0974-360X.2026.00270

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Parent Compound	Key Bioactivity	Experimental Model	Remarks	References
AKBA	Modulates nitric oxide production without affecting immune cell viability	RAW 264.7 murine macrophages (in vitro)	Could be beneficial in inflammation control with minimal immune suppression	⁶⁴
AKBA	Restricts excessive nitric oxide release while maintaining macrophage function	RAW 264.7 murine macrophages (in vitro)	Selective anti-inflammatory potential with low cytotoxicity	⁶⁵
Acetyl-α-boswellic acid	Triggers apoptosis in drug-resistant cancer cells via caspase-3 activation	PC-3 prostate cancer cells (in vitro) and xenograft model (in vivo)	A potential candidate for overcoming chemoresistance	⁶⁶
KBA	Suppresses cell proliferation and induces apoptosis	Cancer cells (in vitro) and prostate cancer xenograft model (in vivo)	Shows strong anticancer potential	⁶⁷
3-Acetyl-11-keto-β-Boswellic Acid	Strong anti-inflammatory and anti-arthritic effects	Arthritis and inflammation models (in vivo)	Effective against inflammatory disorders like arthritis	⁶⁸
α-BA	Inhibits tumor growth and modulates inflammation	Human cancer cell lines (in vitro)	Displays dual anticancer and anti-inflammatory activities	⁶⁹
β-BA	Suppresses cancer cell growth, induces apoptosis	RAW 264.7 murine macrophages (in vitro)	Multifunctional activity against inflammation and cancer	⁷⁰