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Although multiple bioactivities of α-boswellic acid have been reported, the molecular mechanism of its anti-inflammatory action is not yet clear. Hence, glucocorticoid receptor (GR)-mediated anti-inflammation of α-boswellic acid was investigated in this work. Fluorescence polarization assay suggested that α-boswellic acid bound to GR with IC50 value of 658.00 ± 0.21 μM. Upon binding to α-boswellic acid, GR translocated from cytoplasm into nucleus of HeLa cells, facilitating sequential transcriptional regulation of GR-related genes. Luciferase reporter assay suggested that α-boswellic acid lacked GR transcriptional activity, indicating its potential as a dissociative GR ligand. Interestingly, α-boswellic acid selectively modulated the anti-inflammatory gene CBG (marker for GR transrepression), while leaving the “side-effect” gene TAT (marker for GR transactivation) unaffected in HepG2 cells. Furthermore, α-boswellic acid inhibited lipopolysaccharide-stimulated cytokines production in U937 macrophages, confirming its anti-inflammation property in vitro. Molecular docking showed that both hydrogen-bonding and hydrophobic interactions helped to stabilize α-boswellic acid-GR binding. Their binding stability was further confirmed in a 70-ns dynamics simulation. In summary, α-boswellic acid could bind to and translocate GR but did not induce glucocorticoid response element-mediated transcription. Since α-boswellic acid showed the dissociated characteristic that separated transrepression from transactivation, it might be a selective GR modulator against inflammatory disorders.

Boswellic acid (BA) is a pentacyclic terpenoid derived from the gum-resin of Boswellia serrate. It is known for its strong antioxidant, anti-inflammatory, and anticancer properties. It has improved spatial learning and provides neuroprotection against trimethyltin-induced memory impairment. The aim of this study is to evaluate the possible neuroprotective activity of B. serrata extract (BSE) containing BA against fipronil (FPN)-induced neurobehavioral toxicity in Wister male albino rats. Sixty male rats were allocated equally into six groups. The first group served as control; the second and third groups received BSE at two different oral doses (250 or 500 mg/kg body weight [BW], respectively). The fourth group was orally intoxicated with FPN (20 mg/kg BW), whereas the fifth and sixth groups served as preventive groups and co-treated with FPN (20 mg/kg BW) and BSE (250 or 500 mg/kg BW, respectively). The experiment was conducted over 8 weeks period. Results revealed that co-treatment with BSE led to significant (p > 0.05) dose-dependent reduction in malondialdehyde (MDA), nitric oxide (NO), interleukin-6 (IL6), tumor necrosis factors-alpha (TNF-α), nuclear factor Kappa-B (NF-κB), Cyclooxegenase-2 (COX-2), prostaglandin E2 (PGE2), serotonin, and acetylcholine (ACh). Conversely, significant (p > 0.05) up regulation of catalase (CAT), glutathione peroxidase (GSH-Px), gamma-aminobutyric acid (GABA), and acetylcholine esterase (AChE) has reported in BSE-co-treated groups. In addition, significant (p > 0.05) promotion in neurobehaviours, histopathologic imaging of the cerebral, cerebellar, and hippocampal regions, and immunohistochemical expression of caspase-3 and glial fibrillary acidic protein (GFAP) were also reported in the BSE-treated groups in a dose-dependent manner. In conclusion, BSE (500 mg/kg BW) is a natural, promising neuroprotective agent that can mitigate FPN-induced neurobehavioral toxicity via the suppression of oxidative, inflammatory, and apoptotic pathways and relieve neuronal necrosis and astrogliosis.

Background The development of anti-cancer drugs with the ability to inhibit brain metastasis through the blood-brain barrier (BBB) is substantially limited due to the lack of reliable in vitro models. Main methods In this study, the Geltrex™-based Transwell® and microfluidic BBB models were applied to screen the effect of β-boswellic acid (β-BA) on the metastasis of MDA-MB-231 cells through the BBB in static and dynamic conditions, respectively. Major results The toxicity assay revealed that β-BA deteriorates MDA-MB-231 cells, while β-BA had no detectable toxic effects on human umbilical vein endothelial cells (HUVECs) and astrocytes. Trans-endothelial electrical resistance evaluation showed sustainable barrier integrity upon treatment with β-BA. Vimentin expression in HUVECs, evaluated using western blot, confirmed superior barrier integrity in the presence of β-BA. The obtained results were confirmed using an invasion study with a cell tracker and a scanning electron microscope. β-BA significantly inhibited metastasis by 85%, while cisplatin (Cis), a positive control, inhibited cancer cell migration by 12% under static conditions. Upon applying a dynamic BBB model, it was revealed that β-BA-mediated metastasis inhibition was significantly higher than that mediated by Cis. Conclusions and implications In summary, the current study proved the anti-metastatic potential of β-BA in both static and dynamic BBB models. This article is protected by copyright. All rights reserved.

The metal-organic frameworks (MOF) have shown fascinating possibilities in biomedical applications, designing a multifunctional drug delivery system based on the MOF is important. In this study, 5-sulfosalicylic acid and boswellic acids (BAs) were loaded to the pH sensitive zeolitic imidazolate framework-8 (ZIF-8) nanocomposite containing bovine serum albumin (BSA) as the center. The ZIF layer acts as a capsule for the nontoxic storage of 5-sulfosalicylic acid and boswellic acids (BAs) under physiological conditions. The results of the characterization demonstrated the performance of the nanocarrier formation. The pH-sensitive drug release of 5-sulfosalicylic acid was detected due to the innate pH-dependent stability of ZIF-8. An effective pH-sensitive drug delivery system using a 5-sulfosalicylic acid/BSA@ZIF-8, and 5-sulfosalicylic acid/BSA/BAs@ZIF-8, in which the 5-sulfosalicylicacid is not free in physiological pH but it is released at acidic pH (5.0) has been fabricated. The best biocompatibility has been found in 5-sulfosalicylic acid/BSA/BAs@ZIF-8 comparing to the 5-sulfosalicylic acid/BSA, 5-sulfosalicylic acid /BSA/BAs, and 5-sulfosalicylic acid/BSA@ZIF-8. Additionally, 5-sulfosalicylic acid/BSA /BAs@ZIF-8 exhibited higher effectiveness than other compounds against the breast cancer cell line, MCF-7, with less toxicity. It is concluded from the results of the current study that the fabricated ZIF-8 based nanocarrier may potentially provide therapeutic effects on breast cancer cells.

The oleo gum resin of Boswellia serrata belonging to family Burseraceae, is Ayurvedic medicine and has been used for the treatment of inflammatory diseases and arthritic diseases in many countries. Acetyl 11-keto-β-boswellic acid (AKBA) is a potent anti-inflammatory agent obtained from oleo gum resin of Boswellic serrata. Our aim is to extract maximum amount of AKBA from Boswellic serrata by using Three Phase Partitioning (TPP) technique. In the TPP system, the effect of different process parameters such as ammonium sulfate concentration, extraction time, slurry to t-butanol ratio, solute to t-butanol ratio, pH and temperature, was studied in order to enhance the extraction of AKBA. Under the optimized conditions of ammonium sulfate concentration 0–50% (w/v), extraction time 180 min, slurry to t-butanol ratio 1:1 (v/v), solute to solvent ratio 1:25 (w/v), pH 6 and temperature 50 °C, the maximum yield of AKBA was found to be (80 ± 0.33 mg/g). TPP technique gave higher extraction yield of AKBA compared to conventional Soxhlet extraction (18 ± 0.37 mg/g), batch extraction (20 ± 0.45 mg/g), ultrasound assisted extraction (UAE) (24.23 ± 0.28 mg/g). Thus, TPP can be recommended as an attractive and simple technique for the extraction of AKBA from Boswellic serrata.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder of the central nervous system (CNS) that can cause cognition, mobility, and sensory impairments. It is considered one of the most common non-traumatic causes of disability in the world. The aim of the present article was to review the clinical evidence related to medicinal plants in the management of MS symptoms. Electronic databases, including the Cochrane Library, Pubmed, and Scopus, were searched for entries from 1966 to February 2017. Only clinical studies were included in this review. Different medicinal plants have positive effects on MS, including Andrographis paniculata, Boswellia papyrifera, Ruta graveolens, Vaccinium spp., Camellia sinensis, Panax ginseng, Aloysia citrodora, Ginkgo biloba, Oenothera biennis, and Cannabis sativa. C. sativa had the highest level of clinical evidence, supporting its efficacy in MS symptoms. Proanthocyanidins, ginkgo flavone glycosides, ginsenosides, epigallocatechin-3-gallate, cannabinoids (including delta-9-tetrahydrocannabinol and cannabidiol), boswellic acid, and andrographolide were presented as the main bioactive components of medicinal plants with therapeutic benefits in MS. The main complications of MS in which natural drugs were effective include spasticity, fatigue, scotoma, incontinence, urinary urgency, nocturia, memory performance, functional performance, and tremor. Herbal medicines were mostly well tolerated, and the adverse effects were limited to mild to moderate. Further well-designed human studies with a large sample size and longer follow-up period are recommended to confirm the role of medicinal plants and their metabolites in the management of MS.

In spite of being a very potent and promising drug against many types of cancer, docetaxel suffers the disadvantage of low solubility and poor bioavailability rendering it unsuitable for oral administration. Also, the available marketed formulation for intravenous administration has its inherent drawbacks owing to the presence of polysorbate 80. Here, we exploited the anticancer and P-gp inhibitory potential of naturally occurring frankincense oil to fabricate a stable docetaxel loaded nanoemulsified carrier system for oral delivery. The nanoemulsion possessing desirable particle size (122±12nm), polydispersity (0.086±0.007) and zeta potential (-29.8±2.1mV) was stable against all type of physical stresses and simulated physiological conditions tested. The formulation showed higher uptake in Caco-2 cells and inhibited P-gp transporter significantly (P0.05). In MDA-MB-231 cells, it showed less IC

Though several glycosides of various triterpenes are known, but surprisingly no boswellic acid glycosides are reported so far. With a view to make water soluble boswellic acids, prepared glycosides of 11-keto boswellic acid for the first time. Naturally occurring boswellic acids which are anti-inflammatory agents are lipophylic in nature and thus, become a limiting factor in terms of their bioavailability. Among boswellic acids, 11-keto-β-boswellic acid is found to exhibit superior biological activity and hence successfully prepared its glucosyl and maltosyl derivatives viz., 11-keto-β-boswellic acid-24-O-β-D-glucopyranoside (9) and 11-keto-β-boswellic acid-24-O-α-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (15) which are water soluble. Both these compounds are soluble in water to the extent of 10% (w/w) which is very significant.

The limiting factor for the use of Cisplatin in the treatment of different type of cancers is its toxicity and more specifically urogenital toxicity. Oxidative stress is a well-known phenomenon associated with Cisplatin toxicity. However, in Cisplatin treated group, abnormal animal behavior, decreased body weight, cellular and sub-cellular changes in the kidney and sperm abnormality were observed. Our investigation revealed that Cisplatin when administered in combination with a natural product derivative (Urs-12-ene-3α,24β-diol, labeled as IN0523) resulted in significant restoration of body weight and protection against the pathological alteration caused by Cisplatin to kidney and testis. Sperm count and motility were significantly restored near to normal. Cisplatin caused depletion of defense system i.e. glutathione peroxidase, catalase and superoxide dismutase, which were restored close to normal by treatment of IN0523. Reduction in excessive lipid peroxidation induced by Cisplatin was also found by treatment with IN0523. The result suggests that IN0523 is a potential candidate for ameliorating Cisplatin induced toxicity in the kidney and testes at a dose of 100 mg/kg p.o. via inhibiting the oxidative stress/redox status imbalance and may be improving the efflux mechanism.

Objectives: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/ kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity. © 2017 Korean Pharmacopuncture Institute.

Objectives: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.

Background: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. Objective: The aim of this study is to investigate the protective effect of acetyl-11-keto-β-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. Methods: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined. Results: AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology 1) was reduced. Furthermore, the cytoprotective effects of AKBA against UVA-derived oxidative damage were accompanied by modulating expression of inflammatory mediators (i.e., cyclooxygenase-2 and nuclear factor-κB) and NOX1. Conclusions: AKBA protects skin cells from UVA-induced damage by modulating inflammatory mediators and/or ROS production. Therefore, AKBA has potential in the development of skin care products.

Alzheimer's disease (AD) is a complex disease involved oxidative stress and inflammation in its pathogenesis. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid compound from extracts of Boswellia serrata, which has been widely used as an antioxidant and anti-inflammatory agent. The present study was to determine whether AKBA, a novel candidate, could protect against cognitive and neuropathological impairments in AD. We found that AKBA treatment resulted in a significant improvement of learning and memory deficits, a dramatic decrease in cerebral amyloid-β (Aβ) levels and plaque burden, a profound alleviation in oxidative stress and inflammation, and a marked reduction in activated glial cells and synaptic defects in the APPswe/PS1dE9 mice. Furthermore, amyloid precursor protein (APP) processing was remarkably suppressed with AKBA treatment by inhibiting beta-site APP cleaving enzyme 1 (BACE1) protein expression to produce Aβ in the APPswe/PS1dE9 mice brains. Mechanistically, AKBA modulated antioxidant and anti-inflammatory pathways via increasing nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and via declining phosphorylation of inhibitor of nuclear factor-kappa B alpha (IκBα) and p65. Collectively, our findings provide evidence that AKBA protects neurons against oxidative stress and inflammation in AD, and this neuroprotective effect involves the Nrf2/HO-1 and nuclear factor-kappa B (NF-κB) signaling pathways.

BACKGROUND Some substances of plant origin have been reported to exert an effect in reducing intestinal neoplasm development, especially in animal models. Adenomatous polyposis coli multiple intestinal neoplasia - ApcMin/+ is the most studied murine model of genetic intestinal carcinogenesis. AIM To assess whether an enriched nutritional formulation (silymarin, boswellic acid and curcumin) with proven "in vitro" and "in vivo" anti-carcinogenetic properties may prevent inherited intestinal cancer in animal model. METHODS Forty adenomatous polyposis coli multiple intestinal neoplasia - ApcMin/+ mice were used for the study of cancer prevention. They were divided into two groups: 20 assumed standard and 20 enriched diet. At the 110th d animals were sacrificed. In each group, four subgroups received intraperitoneal bromodeoxyuridine injection at different times (24, 48, 72 and 96 h before the sacrifice) in order to assess epithelial turnover. Moreover, we evaluated the following parameters: Intestinal polypoid lesion number and size on autoptic tissue, dysplasia and neoplasia areas by histological examination of the whole small intestine, inflammation by histology and cytokine mRNA expression by real-time polymerase chain reaction, bromodeoxyuridine and TUNEL immuno-fluorescence for epithelial turnover and apoptosis, respectively. Additionally, we performed western blotting analysis for the expression of estrogen alpha and beta receptors, cyclin D1 and cleaved caspase 3 in normal and polypoid tissues. RESULTS Compared to standard, enriched diet reduced the total number (203 vs 416) and the mean ± SD/animal (12.6 ± 5.0 vs 26.0 ± 8.8; P < 0.001) of polypoid lesions. In enriched diet group a reduction in polyp size was observed (P < 0.001). Histological inflammation and pro-inflammatory cytokine expression were similar in both groups. Areas of low-grade dysplasia (P < 0.001) and intestinal carcinoma (IC; P < 0.001) were significantly decreased in enriched diet group. IC was observed in 100% in standard and 85% in enriched formulation assuming animals. Enriched diet showed a faster epithelial migration and an increased apoptosis in normal mucosa and low-grade dysplasia areas (P < 0.001). At western blotting, estrogen receptor beta protein was well expressed in normal mucosa of enriched and standard groups, with a more marked trend associated to the first one. Estrogen receptor alpha was similarly expressed in normal and polypoid mucosa of standard and enriched diet group. Cleaved caspase 3 showed in normal mucosa a stronger signal in enriched than in standard diet. Cyclin D1 was more expressed in standard than enriched diet group of both normal and polypoid tissue. CONCLUSION Our results are suggestive of a chemo-preventive synergic effect of the components (silymarin, boswellic acid and curcumin) of an enriched formulation in inherited IC. This effect may be mediated by the reduction of epithelial proliferation, the increase of apoptosis and the acceleration of villous cell renewal due to dietary formulation intake.

The aim of this study was to develop and validate a new, rapid, sensitive, selective and reliable liquid chromatography–tandem mass spectrometry method for simultaneous determination of 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) and its active metabolite 3-O-Acetyl-11-hydroxy-β-boswellic acid (Ac-11-hydroxy-BA) in rat plasma. Both analytes (AKBA and Ac-11-hydroxy-BA) and the internal standard (IS, ursolic acid) were extracted from 100 μL of rat plasma by protein precipitation. Chromatographic separation was achieved on PRP-H1 RP-C18 column (75 mm × 2 mm, 1.6 μm) using acetonitrile–water (95.5 v/v) as the mobile phase. Mass detection was conducted by electrospray ionization in positive ion multiple reaction monitoring (MRM) mode. A linear dynamic range of 1–1,000 ng/mL for both AKBA and Ac-11-hydroxy-BA was established with mean correlation coefficient (r (1)) of 0.999. Intra- and inter-day precision (% CV) of analysis were found in the range of 1.9–7.4%. The accuracy determined for these analytes ranged from 92.4 to 107.2%. The extraction recoveries for both analytes ranged from 92.6 to 97.3% for spiked plasma samples and were consistent. The % change in stability samples compared to nominal concentration ranged from 0.4 to 4.2%. This method was successfully tested to a pharmacokinetic (PK) study for estimation of AKBA and acetyl-11-hydroxy-BA in rat plasma following oral administration of AKBA. This method has been validated with the advantage of shorter run time that can be used for high-throughput analysis and has been successfully applied to the pharmacokinetic study of AKBA in rats.

Frankincense and myrrha (FM), commonly used as a classical herbal pair, have a wide range of clinical applications and definite anti-inflammatory activity. However, anti-neuroinflammation effects and mechanisms are not clear. In this study, we adopted a lipopolysaccharide (LPS)-induced microglial (BV2) cell model and a network pharmacology method to reveal the anti-neuroinflammatory effects and mechanisms of boswellic acid (BA) and myrrha sesquiterpenes (MS) with different proportions of compatibility. The data showed that the different ratios of BA and MS had different degrees of inhibition of interleukin-1&beta, (IL-1&beta, ), IL-6, and inducible nitric oxide synthase (iNOS) mRNA expression, down-regulated the phosphor-nuclear factor kappa B/nuclear factor kappa B (p-NF-ҡB)/(NF-ҡB), phosphorylated protein kinase b/protein kinase b (p-AKT/AKT), and Toll-like receptor 4 (TLR4) protein expression levels, and increased phospho-PI3 kinase (p-PI3K) protein expression levels. When the ratios of BA and MS were 10:1, 5:1, and 20:1, better effective efficacy was exhibited. According to the correlation analysis between the effect index and bioactive substances, it was suggested that 2-methoxy-5-acetoxy -fruranogermacr-1(10)-en-6-one (Compound 1), 3&alpha, acetyloxylanosta-8,24-dien-21-oic acid (Compound 2), 11-keto-boswellic acid (Compound 3), and 3-acetyl-11-keto-&beta, boswellic acid (Compound 4) made important contributions to the treatment of neuroinflammation. Furthermore, based on the network pharmacological analysis, it was found that these four active compounds acted on 31 targets related to neuroinflammation and were involved in 32 signaling pathways which mainly related to the immune system, cardiovascular system, and nervous system, suggesting that BA and MS could be used to treat neuroinflammation.

Acetyl-11-keto-β-boswellic acid (AKBA), a triterpenoid from Boswellia serrate, is regarded as an angiogenesis inhibitor. However, its toxicity is unknown. The aim of this study was to examine its d...

For centuries, frankincense extracts have been commonly used in traditional medicine, and more recently, in complementary medicine. Therefore, frankincense constituents such as boswellic and lupeolic acids are of considerable therapeutic interest. Sixteen frankincense nutraceuticals were characterized by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), revealing major differences in boswellic and lupeolic acid compositions and total contents, which varied from 0.4% to 35.7%. Frankincense nutraceuticals significantly inhibited the release of proinflammatory cytokines, such as TNF-&alpha, IL-6, and IL-8, by LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood. Moreover, boswellic and lupeolic acid contents correlated with TNF-&alpha, IL-1&beta, IL-6, IL-8, and IL-10 inhibition. The nutraceuticals also exhibited toxicity against the human triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-453, and CAL-51 in vitro. Nutraceuticals with total contents of boswellic and lupeolic acids &gt, 30% were the most active ones against MDA-MB-231 with a half maximal inhibitory concentration (IC50) &le, 7.0 &micro, g/mL. Moreover, a frankincense nutraceutical inhibited tumor growth and induced apoptosis in vivo in breast cancer xenografts grown on the chick chorioallantoic membrane (CAM). Among eight different boswellic and lupeolic acids tested, &beta, ABA exhibited the highest cytotoxicity against MDA-MB-231 with an IC50 = 5.9 &micro, M, inhibited growth of cancer xenografts in vivo, and released proinflammatory cytokines. Its content in nutraceuticals correlated strongly with TNF-, IL-6, and IL-8 release inhibition.

This study is to investigate the protective effect of Acetyl-α-boswellic acid and Acetyl-β-boswellic mixture(α/β-ABA), which is the active ingredients isolated from Frankincense, on actue pancreatitis and its mechanism. Our experimental results showed that 2 μM α/β-ABA reduced production of NO, TNF-α, IL-6, IL-10 and IL-1β in RAW264.7 cells that were stimulated with lipopolysaccharide (LPS) which indicates its anti-inflammatory role. In pancreatitis model induced by caerulein, intra-gastrical administration of 100 mg/kg α/β-ABA relieved inflammatory cells infiltration significantly and attenuated the serum elevation of amylase TNF-α and IL-6 remarkably in mice. Furthermore, α/β-ABA down-regulated mitogen-activated protein kinase (MAPK) family phosphorylated proteins in pancreas, including phosphorylated p38, ERK1/2 and JNK, to reduce the serum inflammatory factors. Finally, α/β-ABA alleviated the pancreatic edema and inflammatory cell infiltration in pancreatitis mice model. This study suggests that α/β-ABA may be targeted for drug development against pancreatitis via modulating MAPKs pathway.

Natural compounds, in recent years, have attracted significant attention for their use in the prevention and treatment of diverse chronic diseases as they are devoid of major toxicities. Boswellic acid (BA), a series of pentacyclic triterpene molecules, is isolated from the gum resin of Boswellia serrata and Boswellia carteri. It proved to be one such agent that has exhibited efficacy against various chronic diseases like arthritis, diabetes, asthma, cancer, inflammatory bowel disease, Parkinson’s disease, Alzheimer’s, etc. The molecular targets attributed to its wide range of biological activities include transcription factors, kinases, enzymes, receptors, growth factors, etc. The present review is an attempt to demonstrate the diverse pharmacological uses of BA, along with its underlying molecular mechanism of action against different ailments. Further, this review also discusses the roadblocks associated with the pharmacokinetics and bioavailability of this promising compound and strategies to overcome those limitations for developing it as an effective drug for the clinical management of chronic diseases.

Background Osteoarthritis is a common canine disease frequently treated with nutritional supplements that often lack independent verification of ingredients, active ingredient concentration, efficacy, or safety. Human supplements containing Boswellia serrata extracts (BSE) with high concentrations of active constituents 3-acetyl-11-keto-β-boswellic acid (AKBA) and 11-keto-β-boswellic acid (KBA) are bioavailable, safe, and efficacious in the alleviation of symptoms of naturally occurring osteoarthritis in people. Thus, oral AKBA and/or KBA supplementation could be a promising novel therapy for dogs with osteoarthritis. The primary objective of this study was to determine the concentrations of AKBA and KBA within six human and seven canine market formulations containing BSE administered to dogs, using a derivation of the previously validated high performance liquid chromatography (HPLC) method. The secondary objective was to compare measured concentrations to label claims. Results The mean concentrations of AKBA and KBA within the formulations tested were 42.3 mg/g AF (0.1–155.7 mg/g AF) and 5.2 mg/g AF (0–24.8 mg/g AF), respectively, with four of the formulations containing an undetectable amount of KBA. None of the market formulations had a label claim for KBA. For the five tested formulations with a label claim for AKBA, the mean percentage of detected AKBA was 173% of the concentration listed on the label (range: 114–224%). Formulations claiming to contain AKBA had a mean AKBA concentration of 98.2 mg/g AF, significantly higher than formulations claiming only to contain BSE (7.4 mg/g AF; p = 0.01). Conclusions This study demonstrated a large variation of boswellic acid concentrations in market formulations claiming to contain BSE, with products claiming to contain AKBA containing higher concentrations of AKBA than other products. There was also a large variation in, and overall high, percent difference between label claims and measured concentrations of AKBA. All products met or exceeded label claims. However, differences between label amounts and detected concentrations confirm the need for independent laboratories to quantify concentrations of active ingredients in supplements containing BSE. This would be necessary prior to the use of these formulations in the research or clinical setting.

Pentacyclic triterpenic acids from oleogum resins of Boswellia species are of considerable therapeutic interest. Yet, their pharmaceutical development is hampered by uncertainties regarding botanical identification and the complexity of triterpenic acid mixtures. Here, a highly sensitive, selective, and accurate method for the simultaneous quantification of eight boswellic and lupeolic acids by high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) was developed. The method was applied to the comparative analysis of 41 oleogum resins of the species B. sacra, B. dalzielli, B. papyrifera, B. serrata, B. carterii, B. neglecta, B. rivae, B. frereana, and B. occulta. Multivariate statistical analysis of the data revealed differences in the triterpenic acid composition that could be assigned to distinct Boswellia species and to their geographic growth location. Extracts of the oleogum resins exhibited cytotoxicity against the human, treatment-resistant, metastatic breast cancer cell line MDA-MB-231. Extracts from B. sacra were the most potent ones with an average IC50 of 8.3 &plusmn, 0.6 &micro, g/mL. The oleogum resin of the B. sacra was further fractionated to enrich different groups of substances. The cytotoxic efficacy against the cancer cells correlates positively with the contents of pentacyclic triterpenic acids in Boswellia extracts.

The 5-lipoxygenase enzyme is a proinflammatory enzyme and produces leukotrienes. Evidence has shown that inflammation contributes to Alzheimer’s disease. On the other hand, boswellic acid derivatives have also been shown to be involved in Alzheimer’s disease. In this study, the interaction of four different derivatives of boswellic acid with 5-lipoxygenase enzyme was investigated using molecular dynamics simulation. The simulation of the enzyme was also carried out alone. Calculation of Cα-RMSD indicates that the enzyme stability is slightly affected by boswellic acid derivatives. Calculating the radius of gyration of the enzyme also shows that the overall shape of the protein is not affected by ligands. The RMSF values of the enzyme residues were calculated in the presence of boswellic acid derivatives and it was compared with that in the absence of ligands. The results show that the flexibility of the enzyme residues is influenced by ligands. The residues, whose flexibility is reduced, are scattered throughout the enzyme. However, their number is great in the N-terminal residue. The binding affinity between boswellic acid derivatives and the enzyme residues was calculated using the measure of conformation factor. The results show that the residues interacting with ligands are in the area of the first domain of enzyme. The results obtained from molecular dynamics simulation are well-consistent with the experimental evidence related to the inhibitory effect of the mentioned compounds with 5-lipoxygenase.

A series of new 11-keto-β-boswellic acid were partially-synthesized by modifying the hydroxyl and carboxylic acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds

Frankincense is an oleogum resin from Boswellia trees of the Burseraceae family. The oleogum resin contains 15–20 % triterpenic acids, including therapeutically active boswellic acids [1]. Extracts...

Background The purpose of this study was to evaluate the long-term efficacy and the safety of a lecithin-based delivery form of boswellic acids from Boswellia serrata (Casperome®) for the prevention of symptoms in otherwise healthy subjects with mild irritable bowel syndrome (IBS). Methods The study included 69 otherwise healthy participants with a mild form of IBS who completed a 6-month follow-up period. In total, 34 subjects were assigned to the standard management (SM) group: diet and, if needed, hyoscine butylbromide (Buscopan®) or papaverine hydrochloride + 10 mg of Atropa belladonna extract; 35 subjects were assigned to supplementation with the Boswellia serrata lecithin-based delivery form (one tablet/day; Casperome®). IBS signs and symptoms were evaluated at inclusion (T0), after 3 (T1) and 6 months (T2). The numbers of patients who needed rescue medication were recorded. Adverse events were also evaluated. Results At baseline, the groups were comparable in terms of demographic and clinical characteristics. At follow-up, compared with the SM group, the Boswellia group showed lower mean score values for almost all self-assed IBS symptoms. A significantly lower need for rescue medications and consultations or medical evaluation/admissions was found in the Boswellia group compared with the SM group. The incidence of minimal adverse events - mainly stipsis - was significantly higher in the SM group. Oxidative stress at T2 was significantly decreased in Boswellia-supplemented subjects. Conclusions Boswellia serrata lecithin-based delivery form (Casperome®) appears to be effective and safe in improving signs and symptoms in IBS subjects who are otherwise healthy, particularly in comparison with symptomatic drug treatment that may cause side effects and stiptis.

Background:The need for safe, effective pain management for osteoarthritis (OA) is important as the number of australian people with OA is expected to grow by 30% from year 2015 to year 2030. Extracts from Boswellia serrata and Curcuma longa are described to have anti-inflammatory and analgesic properties. Clinical studies have also reported efficacy for improving joint pain and stiffness and tolerability. A combination of Boswellia serrata and Curcuma longa formulated extracts might provide benefits in OA pain management.Objectives:To review the literature describing the efficacy, safety and bioavailability of a formulated Boswellia serrata extract enriched with boswellic acids and a Curcuma longa extract formulated with piperine for OA pain management.Methods:PubMed searches for studies reporting efficacy, safety, and/or bioavailability data for Boswellia and Curcumin formulations were conducted on 4 December 2020 with no publication date limitations.Results:For the enriched Boswellia formulation, two clinical studies in OA assessing efficacy and one preclinical bioavailability study were identified1,2,3. For the curcumin formulation, 2 clinical studies were identified4,5. Two double-blind, randomized, parallel, placebo-controlled studies (each N=60) demonstrated significant improvement in Western Ontario and McMaster Universities OA index (WOMAC) pain and stiffness subscale scores in patients with knee OA receiving the enriched Boswellia formulation (100mg/d): In the first study1, a 30-day treatment with enriched Boswellia, compared with placebo, significantly reduced WOMAC pain (−23.6; placebo, −5.6; P2, A 90-day treatment with enriched Boswellia also significantly improved WOMAC pain (−31.1; placebo, −8.4; P4. The results obtained in his study demonstrates that piperine enhances the oral bioavailability of curcumin without side effects. Curcumin/piperine monotherapy (350-400mg curcumin TID) was also shown to significantly reduce WOMAC, VAS and Lequesne’s pain functional index (LPFI) compared to placebo in a randomized double-blind placebo-controlled parallel-group study (N=40)5. In a sub-study that measured inflammatory biomarkers (N=40), there is no significant difference in the magnitude of changes in the inflammatory biomarkers (IL-4, IL-6, hs-CRP, TNF-α, TGF-β and mean ESR between the curcuminoid treatment group and the placebo group (p>0.05)6.Conclusion:Enriched boswellic acid and curcumin/piperine formulations demonstrate efficacy and safety for suitable treatment option: both ingredients, often cited as natural alternatives to address OA pain and stiffness could be evaluated to explore the potential benefit as a formulated combination.References:[1]Vishal et al. Int. J. Med. Sci. 2011, 8[2]Sengupta et al. Int. J. Med. Sci. 2010, 7[3]Sengupta et al. Mol Cell Biochem. 2011, 354:189-197.[4]Shoba et al. Planta Med. 1998 May;64(4):353-6[5]Panahi et al. Phytother. Res. 28: 1625–1631 (2014).[6]Rahimnia A-R et al. Drug Res 2015; 65: 521–525.Disclosure of Interests:Vidhu Sethi Employee of: Employee of GSK Consumer Healthcare, Kamran Siddiqui Employee of: Employee of GSK Consumer Healthcare, Manohar Garg: None declared.

Background:Osteoarthritis (OA) incidence has skyrocketed in the last decade and yet a definitive treatment has still to be found. This worldwide disease is depriving our society from their life quality and has become a grave economic burden. Research on anti-inflammatory tools has been done on traditional Asian medicine. Boswellic acid is a plant-derived molecule from the Boswellia species that has shown to prevent cartilage loss in an OA mouse model[1]. However, the specific mechanism of action is still unclear. The activation of innate immune receptors, such Toll-like receptor 4 (TLR4) has been involved in chondrocyte-mediated inflammatory responses and OA development. Although, boswellic acid has shown an inhibitory effect on TLR4-mediated inflammatory responses little is known about its role on TLR4-mediated chondrocyte inflammatory and catabolic responses.Objectives:Determine the ability of beta boswellic acid (BBA) to block TLR4-mediated innate immune responses in chondrocytes and synoviocytes.Methods:In silicoThe binding affinity of beta boswellic acid (BBA) to TLR4 complex signalling was determined by optimized docking algorithm in the BIO-HPC Research Group facilities.In vitroCellular proteome and secretome profiling (LC-MALDI/TOFF) was used to study inflammatory pathways induced by the agonist of TLR4 (LPS [100ng/ml]) and IL1R (IL1β [0.1ng/ml]). The effect of BBA on TLR4-mediated innate immune responses was determined by RT-PCR, Western Blot and ELISA in primary human OA chondrocytes (hOC), murine ATDC5 chondrocytes, human synoviocytes (SW982) and primary human osteoblasts (hOB). Cell viability was tested using the methyl-thiazolyl-tetrazolium (MTT) reagent. Nitric oxide production in cell culture media was assessed by Griess reaction. Green Malachite Assay was used to semi-quantify the whole phosphoproteome.EthicsThis study was approved by the CEIC (CAEIG 2014/310).Results:Cellular proteome and secretome profiling validated the activation of TLR4 and IL1R signalling by LPS and IL1β ligands and revealed an enrichment in innate immune responses (NF-Kβ, NLRP3, MMPs, Interleukins, etc).Non-toxic doses of BBA [0.5-1000nM] prevented the activation of TLR4 in multiple articular joint cells and inhibited TLR4 & IL1R-dependant innate immune responses at the mRNA and protein level such as inflammatory factors IL6, NOS2, COX2, LCN2, MMP1, -3, -9, -13 and ADAMTS4, among others. Furthermore, NF-Kβ/IKBα and NLRP3/PYCARD/IL1β axis were also severely inhibited after BBA treatment. Moreover, these results were validated by in silico docking analysis that showed BBA interacted with TLR4/NF-Kβ.Conclusion:We prove that BBA inhibit TLR4 & IL1R -dependent innate immune responses in multiple human joint cells (Figure 1). We show that NF-Kβ & NLRP3 signalling, both associated to OA, are blocked (mRNA and protein) after BBA treatment (Figure 1).Our data support previous studies showing the prevention of cartilage loss in an OA animal models by BBA might come from its ability to inhibit TLR4 signalling. In the clinical practice of rheumatologists, Boswellia Serrata could be a useful nutraceutical to manage OA inflammation due to its content in BBA.Figure 1.References:[1]Wang, Q.; Pan, X.; Wong, H.H.; Wagner, C.A.; Lahey, L.J.; Robinson, W.H.; Sokolove, J. Oral and topical boswellic acid attenuates mouse osteoarthritis. Osteoarthr. Cartil.2014, 22, 128–132, doi:10.1016/j.joca.2013.10.012.Acknowledgements:Eloi Franco-Trepat and Ana Lois-Iglesias contributed equally to this work.This research has been funded by the non-profit FER (Fundación Española de Reumatologia /Spanish Foundation of Rheumatology) through the project “Búsqueda de nuevos fármacos bloqueantes de la inflamación asociada a TLR4 en condrocitos humanos artrósicos”.Disclosure of Interests:None declared

Wear debris-induced osteoclast accumulation around implants plays a crucial role during the progression of periprosthetic osteolysis (PPO). We have confirmed that acetyl-11-keto-β-boswellic acid (AKBA) promotes bone formation and protects against particle-induced bone destruction in vivo. However, the effect of AKBA on titanium-induced bone resorption is unknown. In this study, we detected the inhibitory effect of AKBA on titanium-induced bone erosion in vivo and used RAW264.7 cells and bone marrow macrophages (BMMs) to investigate the effect and underlying mechanism of AKBA on the differentiation and resorptive function of osteoclasts. Our findings revealed that AKBA inhibited particle-induced bone loss and osteoclast formation in vivo. Furthermore, AKBA exerted inhibitory effects on RANKL-induced osteoclastogenesis, osteoclastic ring-dependent resorption and the expression of osteoclast marker genes via the ERK signaling pathway in vitro. Our data further established the protective effect of AKBA on titanium particle-induced bone erosion from a new perspective of bone erosion prevention, strongly confirming that AKBA is an appropriate agent for protection against PPO.

In several parts of the world, Boswellia sacra Fluck. is one of the most commonly used herbs for the treatment of arthritis. Its usage should be validated in light of recent findings of haematotoxicity. This study was aimed to determine the effect of chronic administration of standardized methanolic extract of frankincense on blood cell count in experimental animals. Using high-performance liquid chromatography, the active constituents of B. sacra extract; boswellic acids were analyzed. The effect of three different doses of the extract (250, 500, and 1000 mg/kg) on different blood cells and associated parameters was investigated. The behavior, food, and water consumption of the rats were recorded. Boswellic acids were present in varying amounts with α-boswellic acid and β-boswellic acid present in more amounts compared to other boswellic acids in the extract. All three doses tested had no effect on the animals’ behavior, food consumption, or weight gain. The administration of a low (500 mg/kg) and high (1000 mg/kg) dose of the extract resulted in a non-dose dependent reduction in MCH ( p

Boswellic acid (BA) is an ancient herbal drug prescribed in the Indian traditional medicine systems (Ayurveda) for treatment of coughs, colds, hoarseness, bronchitis, asthma, dyspnea and diarrhea. Current research suggests it also has therapeutic potential in modern medical practice. Therefore, it is of interest to the research community to consolidate the preclinical and clinical findings on BA. The aim of this review was to comprehensively cover the plant sources, phytochemistry and physicochemical properties of BA along with its medicinal properties, safety, toxicity, and regulatory status. The review also discussed the challenges associated with drug delivery and some feasible approaches for addressing these. Four electronic databases (Scifinder, Unbound Medline, PubMed and Science Direct) and two internet search engines (Scirus and Google Scholar) were extensively searched without any time constraint. The many studies discussed in the review indicated therapeutic potential for BA in the treatment of a range of chronic diseases including arthritis, cancer, asthma and diabetes. It is hoped that this review will help researchers identify relevant research questions leading to the development of effective formulations and a better understanding of the safety of BA, with the aim of promoting it as a mainstream treatment for various diseases in clinical practice.

Fifteen stereoisomers of boswellic acid analogues bearing 2-OH, 24-OH, 3-keto or 2-OH, 3-OH, 24-OH groups were synthesised and their structures were confirmed using 1 H NMR, 13 C NMR, 2D NMR and HRMS. The cytotoxic activities of these compounds toward three human tumor cell lines, K562, PC3 and A549, were evaluated. Preliminary biological evaluation indicated most of these compounds exhibited cytotoxic activity comparable to that of 3- O -acetyl-11-keto-β-boswellic acid (AKBA). Notably, several analogues exhibited relatively stronger cytotoxicity, with IC 50 values less than 10 μM against A549 and PC3 cell lines. For the 24-OH series of BAs analogues, structure-activity relationship (SAR) analysis indicated that the stereochemical configurations of compounds incorporating 2-OH, 3-keto or 2-OH, 3-OH group pairs could not predictably or markedly impact cytotoxic activity, except when 2β-OH and/or 3β-OH were present. Esterification of 2-OH, 3-OH and 24-OH groups tended to decrease cytotoxicity.

Ethnopharmacological relevance Increasing research on traditional herbal medicines and their phytoconstituents has recognized their usefulness in complementary as adjuvant to chemotherapy in various types of cancers. The oleo-gum resin of Boswellia serrata tree is one such folk medicine, which has been traditionally used for religious, cosmetic as well as medical purposes since ages. The oleo-gum resin of the plant has been used in traditional medicine to treat variety of conditions including inflammatory diseases like arthritis, asthma, chronic pain, bowel conditions and many other diseases. This review presents an overview of scientific studies on cytotoxic and antitumor properties of B. serrata and its constituents. Materials and methods Literature search was carried out for activities of B. serrata and various isolated boswellic acids such as β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid reported in various cancer types in vitro as well as in vivo. Results The triterpenoidal fraction of B. serrata (containing boswellic acids) is responsible for the cytotoxic and antitumor properties. Among the screened compounds, 3-O-acetyl-11-keto-β-boswellic acid has been found to be most promising cytotoxic molecule. The cytotoxic and antitumor effects are mainly due to induction of apoptosis through caspase activation, increased Bax expression, NF-κB down regulation and induction of poly (ADP)-ribose polymerase (PARP) cleavage. Conclusions Boswellic acids appear to be promising candidates for anticancer drug development in future. However, further in vivo studies are needed. Studies in combination with clinically used anticancer drugs and QSAR studies on individual boswellic acid also need to be carried out.

The Boswellia gum resin extracts have been used in traditional medicines because of their remarkable anti-inflammatory properties. Nowadays, these extracts are on the market as food supplements. β-Boswellic acid (βBA) is one of the main pentacyclic triterpene components, among the family of BAs, of the Boswellia gum resins. BAs have been broadly studied and are well known for their wide anti-inflammatory and potential anticancer properties. In this paper, a mass spectrometry-based chemoproteomic approach has been applied to characterize the whole βBA interacting profile. Among the large numbers of proteins fished out, proteasome, 14-3-3 and some ribosomal proteins were considered the most interesting targets strictly connected to the modulation of the cancer progression. In particular, because of their recent assessment as innovative chemotherapeutic targets, the ribosomal proteins were considered the most attractive βBA partners, and the biological role of their interaction with the natural compound has been evaluated. Copyright © 2016 John Wiley & Sons, Ltd.

Despite the extensive research carried out in the field of cancer therapeutics, cancer is one of the most dreadful diseases in the world with no definitive treatment to date. The key attributes responsible for this are the various limiting factors associated with conventional chemotherapeutics that primarily include adverse side-effects and development of chemoresistance. Hence, there is an utter need to find compounds that are highly safe and efficacious for the prevention and treatment of cancer. Boswellic acid, a group of pentacyclic compounds, seems to be promising enough due to its inherent anti-cancerous properties. Considering this perspective, the present review highlights the established studies related to the anti-cancer potential of boswellic acid against different cancer types. The molecular mechanisms underlying the targets of boswellic acid that are accountable for its potent anti-cancer effect are also discussed. Overall, this review projects the pieces of evidence that reveal the potential of boswellic acid as a suitable candidate that can be appropriately developed and designed into a promising anti-cancer drug.

INTRODUCTION A high-fat diet is one of the main dietary factors promoting platelet aggregation. The present study was conducted to elucidate the involvement of boswellic acid (BA) on the platelet hyperaggregability in HFD-fed rats. As platelet hyperaggregability in HFD rats is closely linked to inflammation and enhanced free radical production, the present study was extended to evaluate the anti-inflammatory and anti-oxidative effect of BA on HFD-promoted platelet aggregation. MATERIAL AND METHODS Rats were assigned to normal, HFD-fed, aspirin-treated (30 mg/kg), and BA-treated (250 and 500 mg/kg) groups. RESULTS Boswellic acid administration in a high dose was effective in attenuating the severity of hyperlipidemia and platelet aggregation, indicated by lower collagen/epinephrine-induced platelet aggregation, as evidenced by the significant increase (p < 0.05) in the circulating platelet count and reduction in the number of thrombi in the lungs. Moreover, it attenuated the oxidative stress and the intensity of inflammatory mediators associated with platelet hyperaggregability, as evidenced by the inhibitory effects on interlukin-1β, COX-2 and tumor necrosis factor-α, indicating that the antiplatelet activity of BA is likely a consequence of controlling oxidative stress and inflammation. CONCLUSIONS The present data suggest that BA shows a promising anti-aggregatory effect by attenuating the enhanced hyperlipidemia, oxidative stress and inflammation associated with HFD.

In consideration of the increasing popularity of frankincense and the widely published quality problems associated with botanical dietary supplements, a survey was conducted for the first time on the quality of frankincense containing botanical dietary supplements. Six US products representing 78 % of the units sold and 70 % of the market value, and 11 European products representing 30 % of the units sold and 40 % of the market value were tested for their boswellic acid composition profile, label compliance, and claimed health benefits. Special focus was also set on the statements made with regard to the frankincense applied. Only five products out of seventeen disclosed all relevant information for the Boswellia extract, mentioning the species, the part of plant used, and the boswellic acid content. Whereas all products but one claimed to use Boswellia serrata, three products did not mention the resin as the part applied and 10 products did not declare the boswellic acid content. Apart from the different boswellic acid composition determined with a sensitive LC/MS method, 41 % of the products did not comply with the label declaration. Hence, one product from Italy did not contain any of the six characteristic boswellic acids (KBA, AKBA, αBA, βBA, AαBA, AβBA) at all and another US product contained only traces, suggesting the absence of frankincense or the use of Boswellia frereana instead of B. serrata. In another product, the ratios of the individual boswellic acids were different from B. serrata gum resin, indicating the use of another species such as Boswellia sacra or Boswellia carterii. Furthermore, two products revealed different boswellic acid contents from those declared on the label. Further, two products did not declare the use of manipulated Boswellia gum resin extract being enriched in acetyl-11-keto-boswellic acid content reaching up to 66 %. In addition, consumers could be misled by outdated literature or references to in vitro studies performed at dosages that can never be achieved in humans following oral administration. In summary, this survey reveals that in spite of increased regulations on botanical dietary supplements, the problem of mislabeling still exists and needs to be addressed by the manufacturers, so that consumers get greater confidence in the botanical dietary supplements they use.

Boswellic acids (BAs) are isolated from oleo gum of Boswellia serrata and are mainly used as potential anti-inflammatory, hypolipidemic, immunomodulatory, and antitumor agents. Pharmacokinetic investigations of BAs uncover its poor bioavailability through digestive system thus creates a need for improved therapeutic responses which can possibly be achieved by developing formulations through novel delivery system.Present study was conducted to design topical BA-loaded proniosomal gel for the management of inflammatory disorders with enhanced bioavailability.Nonionic surfactant vesicles were prepared using the coacervation phase separation method. A central composite design was employed to statistically optimize formulation variables using Design-Expert software. Three independent variables were evaluated: amount of surfactant (XThe optimum formulation (F10) displayed spherical bi-layered vesicles under transmission electron microscopy with optimum particle size of 707.9 nm and high entrapment efficiency as 98.52%. In vitro skin permeation study demonstrated the most sustained release of 84.83 ± 0.153 mg/cmThe present study exhibited that BA-loaded proniosomal gel was better in terms of absorption, bioavailability, and release kinetics.

A series of β-boswellic acid derivatives were synthesized and evaluated for anticancer activity. One of the lead analog 4f displayed significant anticancer activity against a panel of cancer cells as well as substantially inhibited colony formation in HCT-116 cells. Furthermore, 4f was found to be a potent inducer of apoptosis confirmed by loss of mitochondrial membrane potential, DAPI staining, Western blotting and ROS generation.

A library of boswellic acid analogues were synthesized and tested for their anti-inflammatory potential on key inflammatory mediators, TNF-α and IL-6. The study led to the identification of lead compounds showing significant inhibition of the cytokines, TNF-α and IL-6 both in vitro and in vivo.