Acetyl-11-keto-β-boswellic Acid Research Articles

Novel formulations ameliorate osteoarthritis in rats by inhibiting inflammation and oxidative stress.

The study tested new oral plant-based formulations (F) on rats with monosodium iodoacetate (MIA)-induced osteoarthritis, measuring inflammation, antioxidant levels, paw size, stride, and analyzing knee joint images. Fifty-six female Sprague Dawley rats were allocated into 8 groups: (1) Control, (2) MIA (OA induced with MIA), (3) MIA + F1 [curcuminoids+gingerols+acetyl-11-keto-β boswellic acid (AKBA)], (4) MIA + F2 (curcuminoids+Withania glycosides+AKBA), (5) MIA + F3 (curcuminoids+total withanolides+AKBA), (6) MIA + F4 (curcuminoids, AKBA), (7) MIA + UCII (type II collagen), and (8) MIA + GCHON (Glucosamine Chondroitin). Treatments F1 to F4 reduced right joint diameter and improved stride length and paw area in OA rats. Despite improvements with treatments F1 to F4, there was no significant difference between these groups (p > .05). In OA animals, F1 to F4 treatments decreased MDA levels and increased antioxidant enzymes activities (p < .001). This was done by reducing levels of inflammatory markers and enzymes like IL-1β, IL-6, MMP-8, TNF-α, CRP, COMP, and LOX-5, while increasing the anti-inflammatory cytokine IL-10. In conclusion, these plant-based treatments significantly reduced osteoarthritis severity, slowed disease progression by reducing inflammation, and protected joints from damage, showing a protective effect in rats with induced osteoarthritis, likely due to their anti-inflammatory and antioxidant properties.

Single-dose comparative pharmacokinetic/pharmacodynamic study of a micellar formulation versus a native Boswellia serrata dry extract in healthy volunteers

BackgroundExtracts of oleogum resins of Boswellia trees possess anti-inflammatory activities. Micellar formulations have been developed to increase the oral bioavailability of bioactive boswellic and lupeolic acids. PurposeThe current single-dose crossover clinical trial compares for the first time pharmacokinetics/pharmacodynamics of two Boswellia serrata nutraceuticals, native Biotikon® BS-85 and micellar Boswellia-Loges®. MethodsAfter oral administration of the study preparations (800 mg) to 20 healthy volunteers, plasma concentrations of 8 boswellic and lupeolic acids were measured by using HPLC-MS/MS for up to 48 h Blood samples collected 2 and 5 h after drug administration were stimulated for 24 h with endotoxic lipopolysaccharide. The release of proinflammatory cytokines analyzed by flow cytometry was used as readout of the pharmacodynamic properties of the preparations. Registration: German Clinical Trials Register (DRKS) No. DRKS00027369. ResultsAdministration of the micellar extract significantly increased Cmax, AUC0–48, and shortened Tmax for all boswellic and lupeolic acids compared to native extract. Accordingly, their relative bioavailability increased to 1,720-4,291 % with the highest difference for acetyl-11-keto-β-boswellic acid (AKBA). Both preparations reduced the release of TNF-α and the native formulation diminished also IL-1β and IL-6. However, no significant differences were observed between the preparations, except for a higher decrease in IL-1β by the native formulation Biotikon® BS-85. In a lymphocytic gene reporter cell line, both nutraceuticals similarly inhibited the NF-κB transcription factor activity as well as the TNF-α release, yet the native formulation Biotikon®BS-85 was more efficient in inhibiting TNF-α. ConclusionAdministration of the micellar Boswellia serrata nutraceutical increased the oral bioavailability of boswellic and lupeolic acids. Yet, the increase in plasma concentration did not enhance the anti-inflammatory efficacy of the micellar extract compared to the native extract in this ex vivo model.

Acetyl-11-keto-β-boswellic acid restrains the progression of synovitis in osteoarthritis via the Nrf2/HO-1 pathway.

Synovial inflammation plays a key role in osteoarthritis (OA) pathogenesis. Fibroblast-like synoviocytes (FLSs) represent a distinct cell subpopulation within the synovium, and their unique phenotypic alterations are considered significant contributors to inflammation and fibrotic responses. The underlying mechanism by which acetyl-11-keto-β-boswellic acid (AKBA) modulates FLS activation remains unclear. This study aims to assess the beneficial effects of AKBA through both in vitro and in vivo investigations. Network pharmacology evaluation is used to identify potential targets of AKBA in OA. We evaluate the effects of AKBA on FLSs activation in vitro and the regulatory role of AKBA on the Nrf2/HO-1 signaling pathway. ML385 (an Nrf2 inhibitor) is used to verify the binding of AKBA to its target in FLSs. We validate the in vivo efficacy of AKBA in alleviating OA using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT+DMM) in a rat model. Network pharmacological analysis reveals the potential effect of AKBA on OA. AKBA effectively attenuates lipopolysaccharide (LPS)-induced abnormal migration and invasion and the production of inflammatory mediators, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) in FLSs, contributing to the restoration of the synovial microenvironment. After treatment with ML385, the effect of AKBA on FLSs is reversed. In vivo studies demonstrate that AKBA mitigates synovial inflammation and fibrotic responses induced by ACLT+DMM in rats via activation of the Nrf2/HO-1 axis. AKBA exhibits theoretical potential for alleviating OA progression through the Nrf2/HO-1 pathway and represents a viable therapeutic candidate for this patient population.

Antimicrobial topical polymeric films loaded with Acetyl-11-keto-β-boswellic acid (AKBA), boswellic acid and silver nanoparticles: Optimization, characterization, and biological activity

The study examined the antimicrobial and antioxidant potential of pure Acetyl-11-keto-β-boswellic acid (AKBA), boswellic acid (70%) and AKBA loaded nanoparticles as topical polymeric films. The optimized concentration (0.05 % w/v) of pure AKBA, boswellic acid (BA), and AKBA loaded silver nanoparticles were used to study its impact on film characteristics. Carboxymethyl cellulose (CMC), sodium alginate (SA), and gelatin (Ge) composite films were prepared in this study. The polymeric films were evaluated for their biological (antioxidant and antimicrobial activities) and mechanical characteristics such as tensile strength (TS) and elongation (%). Moreover, other parameters including water barrier properties and color attributes of the film were also evaluated. Furthermore, assessments were conducted using analytical techniques like FTIR, XRD, and SEM. Surface analysis revealed that AgNP precipitation led to a few particles in the film structure. Overall, the results indicate a relatively consistent microstructure. Moreover, due to the addition of AKBA, BA, and AgNPs, a significant decrease in TS, moisture content, water solubility, and water vapor permeation was observed. The films transparency also showed a decreasing trend, and the color analysis revealed decreasing yellowness (b*) of the films. Importantly, a significant increase in antioxidant activity against DPPH free radicals and ABTS cations was observed in the CSG films. Additionally, the AgNP-AKBA loaded films displayed significant antifungal activity against C. albicans. Moreover, the molecular docking analysis revealed the inter-molecular interactions between the AKBA, AgNPs, and composite films. The docking results indicate good binding of AKBA and silver nanoparticles with gelatin and carboxymethyl cellulosemolecules. In conclusion, these polymeric films have potential as novel materials with significant antioxidant and antifungal activities.

Boswellic acid as a potential adjunct for bone healing after endodontic surgery: In vitro study

Abstract Introduction: The role of Acetyl -11-keto-β-boswellic acid (AKBA) in regulating osteoblast differentiation was recently brought to light. Therefore, the current study was designed to explore the osteogenic differentiation capability of AKBA on bone marrow mesenchymal stem cells (BMMSCs) as a potential therapeutic agent to accelerate the healing process in apicoectomy. Materials and Methods: BMMSCs were characterized by flow cytometry. Cellular viability and proliferation assays were used with different concentrations of AKBA. Cells were divided into 5 groups to test osteogenic differentiation: Group I: negative control, Group II: positive control, Group III: BMMSCs were treated with 1 μM AKBA, Group IV: BMMSCs were treated with 0.1 μM AKBA, and Group V: BMMSCs were treated with 0.01 μM AKBA. Mineralization assays and gene expression analysis were assessed, and the significance difference between groups was established at P &lt; 0.05. Results: The flow cytometry analysis demonstrated that BMMSCs had positive expression for mesenchymal stem cell marker and negative expression for hematopoietic markers. The concentration of 0.01 μM gave significantly higher cell density than the untreated cells after 7 days (P &lt; 0.05). Cells treated with 0.1 and 0.01 μM AKBA revealed a significantly higher ALP activity, alizarin red, and von Kossa staining than control groups (P &lt; 0.05). High expression of osteogenic genes was detected in BMMSCs treated with 0.1 μM AKBA (P &lt; 0.05). Conclusions: It was declared that the concentration of 0.1 μM AKBA has no toxicity on BMMSC viability and proliferation with an impact on BMMSC osteogenic differentiation. Therefore, AKBA (0.01 μM) could be used in bone regeneration during periradicular surgery.

Species-Specific quantification of bioactive boswellic acids in Boswellia resin using NIR spectroscopy, HPLC and Multivariate data analysis

The bioactive compounds Acetyl-11-keto-β-boswellic acid (AKBA) and 11-keto-β-boswellic acid (KBA), found in the resin of the Boswellia tree, exhibit anti-inflammatory properties, rendering Boswellia resin an intriguing natural medicinal products. However, the content of boswellic acids varies across different Boswellia species and proper knowledge of its species-dependent nature, as well as alternatives to the resource- and time-intensive HPLC analysis, are lacking. Here we present a comprehensive investigation into the boswellic acid content of seven Boswellia species from ten countries and introduce a novel and non-destructive Near-Infrared spectroscopy method for predicting boswellic acid concentrations in solid resin samples. The HPLC-UV reference analysis revealed AKBA concentrations of up to 7.27 % (w/w) with KBA concentrations reaching up to 1.28 % (w/w). Principal Component Analysis of the HPLC and NIR spectroscopy data unveiled species-specific variations, facilitating differentiation based on boswellic acid content, characteristic chromatograms and NIR spectra. Using the HPLC-UV quantification as reference, we developed a Partial Least Squares regression model based on NIR spectra of the resin samples. This model demonstrated highly satisfactory predictive capabilities for AKBA content, achieving a root mean square error of prediction of 0.74 % (w/w) and an R2val of 0.79 in independent test set validation. Although the model was less effective for predicting KBA content, it still offered valuable estimates. The spectroscopic method introduced in this study provides a cost-effective and solvent-free approach for predicting boswellic acid content, demonstrating the potential for application in non-laboratory settings through the use of miniaturized NIR spectrometers. Consequently, this method aligns well with the principles of green chemistry and addresses the growing demand for alternative analytical techniques.

Synthesis of Novel Acetyl-11-keto-β-boswellic Acid Derivatives as Potential Anti-GBM Agents.

Acetyl-11-keto-β-boswellic acid (AKBA) is known to inhibit the growth of glioblastoma (GBM) cells and subcutaneous GBM. A series of acetyl-11-keto-β-boswellic acid (AKBA) derivatives containing the oxime-ester functionality or amide side chains were synthesized, and their anti-GBM activities were evaluated. Some of these compounds exhibited significant inhibitory activity against cell proliferation in U87 and U251 GBM cell lines, with IC50 values in the micromolar concentration range. Cellular thermal shift analysis showed that A-01 and A-10 improved the thermal stability of FOXM1, indicating that these highly active compounds may directly bind to FOXM1 in cells. Docking studies of the two most active compounds, A-01 and A-10, revealed key interactions between these compounds and the active site of FOXM1, in which the amide moiety at the C-24 position was essential for improving the activity. These results suggested that A-10 is a suitable lead molecule for the development of FOXM1 inhibitors. Thus, the rational design of AKBA derivatives with amide side chains holds significant potential for discovering of a new class of triterpenoids capable of inhibiting GBM cell proliferation.

Effect of Boswellic Acid on Viability of Dental Pulp Stem Cells Compared to the Commonly Used Intracanal Medications: An In Vitro Study.

This study was aimed at evaluating the effect of acetyl-11-keto-β-boswellic acid (AKBA) on dental pulp stem cells (DPSCs) viability and proliferation to be used as a potential root canal medicament. Dental pulp stem cells were isolated from human third molars. The phenotypic characterization of DPSCs was verified by flow cytometry analysis. The viability assay was performed using the methyl-thiazoltetrazolium (MTT) assay. Cells were treated with different concentration of triple antibiotic paste (TAP) and calcium hydroxide Ca(OH2) (5, 2.5, 1, 0.5, and 0.25 mg/mL), AKBA (10, 5, 1, 0.1, and 0.01 µM). All experiments were done in separate triplicate experiments. Results: Dental pulp stem cells were characterized by flow cytometry. Cells treated with Ca(OH)2 (1, 2.5, and 5 mg/mL) showed significantly reduced viability compared with the control cells (p < 0.05). Dental pulp stem cells treated with 1, 2.5, and 5 mg/mL TAP resulted in a significant decrease in viability (p < 0.05). Cells treated with AKBA in concentrations (1, 0.1, and 0.01 µM) demonstrated higher viability than the control group (p < 0.05), while AKBA in concentrations (5 and 10 µM) showed equal or decreased viability than the control group. (p > 0.05). Regarding cell density assay, AKBA showed significant increase in cell density after 5 and 7 days compared with cells medicated with TAP and Ca(OH)2 while TAP revealed marked reduction in cell density in all the tested intervals. Acetyl-11-keto-β-boswellic acid in lower concentrations (0.01, 0.1, and 1 µM) demonstrated superior cell viability than TAP and Ca(OH)2, and it may possess the potential to be an intracanal medicament in regenerative endodontics. Studying the effect of different potential root canal medicaments and their capability to induce DPSCs proliferation might be of value. The influence of AKBA on the viability and proliferation of DPSCs tested in this study sheds light on its use as a potential intracanal medication especially in regenerative endodontics. How to cite this article: Amer NA, Badawi MF, Elbeltagi MG, et al. Effect of Boswellic Acid on Viability of Dental Pulp Stem Cells Compared to the Commonly Used Intracanal Medications: An In Vitro Study. J Contemp Dent Pract 2023;24(12):957-966.

Neuro-protective Effect of Acetyl-11-keto-β-boswellic Acid in a Rat Model of Scopolamine-induced Cholinergic Dysfunction.

Acetyl-11-keto-β-boswellic acid (AKBA) is a major component of the oleo-gum resin of B. serrata with multiple pharmacological activities. The objective of this study was to explore the underlying mechanisms of neuroprotective potential of AKBA against scopolamine-mediated cholinergic dysfunction and memory deficits in rats. The rats received AKBA (2.5, 5, and 10 mg/kg, oral) for 21 days. In the third week, scopolamine was administered 30 min before the Morris water maze and passive avoidance tests. In order to perform biochemical assessments, the hippocampus and prefrontal cortex were extracted from the rats euthanized under deep anesthesia. In the MWM test, treatment with AKBA (5 and 10 mg/kg) decreased the latency and distance to find the platform. Moreover, in the PA test, AKBA remarkably increased latency to darkness and stayed time in lightness while decreasing the frequency of entry and time in the darkness. According to the biochemical assessments, AKBA decreased acetylcholinesterase activity and malondialdehyde levels while increasing antioxidant enzymes and total thiol content. Furthermore, AKBA administration restored the hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and mRNA expression of B-cell lymphoma (Bcl)- 2 and Bcl-2- associated X genes in brain tissue of scopolamine-injured rats. The results suggested the effectiveness of AKBA in preventing learning and memory dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by modulating BDNF, cholinergic system function, oxidative stress, and apoptotic markers.

Acetyl-11-Keto-β-Boswellic Acid Accelerates the Repair of Spinal Cord Injury in Rats by Resisting Neuronal Pyroptosis with Nrf2.

The primary aim of this study is to delve into the potential of Acetyl-11-keto-β-boswellic acid (AKBA) in ameliorating neuronal damage induced by acute spinal cord injury, as well as to unravel the intricate underlying mechanisms. A cohort of 40 Sprague-Dawley rats was meticulously categorized into four groups. Following a seven-day oral administration of AKBA, damaged spinal cord samples were meticulously procured for Nissl staining and electron microscopy to assess neuronal demise. Employing ELISA, immunofluorescence, Western blot (WB), and quantitative polymerase chain reaction (qPCR), the modulatory effects of AKBA within the context of spinal cord injury were comprehensively evaluated. Furthermore, employing an ex vivo extraction of spinal cord neurons, an ATP + LPS-induced pyroptotic injury model was established. The model was subsequently subjected to Nrf2 inhibition, followed by a battery of assessments involving ELISA, DCFH-DA staining, flow cytometry, immunofluorescence, and WB to decipher the effects of AKBA on the spinal cord neuron pyroptosis model. By engaging the Nrf2-ROS-NLRP3 pathway, AKBA exerted a repressive influence on the expression of the pyroptotic initiator protein Caspase-1, thereby mitigating the release of GSDMD and alleviating pyroptosis. Additionally, AKBA demonstrated the ability to attenuate the release of IL-18 and IL-1β, curbing neuronal loss and expediting the restorative processes within the context of spinal cord injury. Our study elucidates that AKBA can reduce spinal cord neuronal apoptosis, providing a basis for the development of AKBA as a clinical treatment for spinal cord injury.

Acetyl-11-Keto-β-Boswellic Acid and Incensole Acetate Attenuate Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation and Oxidative Stress.

Boswellia serrata has been used in traditional medicine to treat various inflammatory diseases. Acetyl-11-keto-β-boswellic acid (AKBA) and incensole acetate (IA) are two active ingredients of B. serrata that possess anti-inflammatory and antioxidant activities. The present study aimed to investigate the protective effects of AKBA and IA against lipopolysaccharide (LPS)- induced acute kidney injury (AKI) in rats. Wistar rats were intraperitoneally pretreated with AKBA or IA for 2 weeks. After 30 min, an LPS injection was applied to induce AKI. Blood samples and kidney tissues were collected and used for biochemical assays. AKBA and IA not only significantly decreased interleukin-6 as a marker of renal inflammation but also attenuated the oxidative stress markers in kidney tissues. AKBA and IA also remarkably decreased serum creatinine and blood urea nitrogen. These results suggest that AKBA and IA have protective effects against AKI in rats through regulating inflammation and oxidative stress.

AKBA alleviates experimental pancreatitis by inhibiting oxidative stress in Macrophages through the Nrf2/HO-1 pathway.

Acute pancreatitis (AP) is an inflammatory condition of the pancreas characterized by oxidative stress and inflammation in its pathophysiology. Acetyl-11-keto-β-boswellic acid (AKBA) is an active triterpenoid with antioxidant activity. This article seeks to assess the impact of AKBA on AP and investigate its underlying mechanisms. AP was induced in wild-type, Lyz2+/cre Nrf2fl/fl mice and Pdx1+/cre Nrf2fl/fl mice by caerulein. Serum amylase and lipase levels, along with histological grading, were utilized to evaluate the severity of AP. Murine bone marrow-derived macrophages (BMDMs) were isolated, cultured, and polarized to the M1 subtype. Flow cytometry and ELISA were utilized to identify the macrophage phenotype. Alterations in oxidative stress damage and intracellular ROS were observed. Nrf2/HO-1 signaling pathways were also evaluated. In a caerulein-induced mouse model of AP, treatment with AKBA reduced blood amylase and lipase activity and ameliorated pancreatic tissue histological and pathological features. Furthermore, AKBA significantly mitigated oxidative stress-induced damage and induced the expression of Nrf2 and HO-1 protein. Additionally, by using conditional knockout mice (Lyz2+/cre Nrf2fl/fl and Pdx1+/cre Nrf2fl/fl mice), we verified that Nrf2 primarily functions in macrophages rather than acinar cells. In vitro, AKBA inhibits pro-inflammatory M1-subtype macrophage polarization and reduces ROS generation through Nrf2/HO-1 oxidative stress pathway. Moreover, the protective effects of AKBA against AP were abolished in myeloid-specific Nrf2-deficient mice and BMDMs. Molecular docking results revealed interactions between AKBA and Nrf2. Our results confirm that AKBA exerts protective effects against AP in mice by inhibiting oxidative stress in macrophages through the Nrf2/HO-1 Pathway.

Antiproliferative and cell cycle arrest potentials of 3-O-acetyl-11-keto-β-boswellic acid against MCF-7 cells in vitro

IntroductionCancer is a major issue in medical science with increasing death cases every year worldwide. Therefore, searching for alternatives and nonorthodox methods of treatments with high efficiency, selectivity and less toxicity is the main goal in fighting cancer. Acetyl-11-keto-β-boswellic acid (AKBA), is a derivative pentacyclic triterpenoid that exhibited various biological activities with potential anti-tumoral agents. In this research, AKBA was utilized to examine the potential cytotoxic activity against MCF-7 cells in vitro and monitor the cellular and morphological changes with a prospective impact on apoptosis induction. MethodsThe cytotoxic activity of AKBA was measured by 3(4,5dimethylthiazole- 2-yl)-2,5 diphyneltetrazolium bromide (MTT) assay. A dose-dependent inhibition in MCF-7 cell viability was detected. The clonogenicity of MCF-7 cells was significantly suppressed by AKBA increment in comparison with untreated cells. ResultMorphologically, exposure of MCF-7 cells to high AKBA concentrations caused changes in cell nuclear morphology which was indicated by increasing in nuclear size and cell permeability intensity. The mitochondrial membrane potential (ΔΨm) was reduced by increasing AKBA concentration with a significant release of cytochrome c. Acridine orange/ethidium bromide dual staining experiment confirmed that MCF-7 cells treated with AKBA (IC50 concentration) displayed a late stage of apoptosis indicated by intense and bright reddish colour. ConclusionA significant increase in reactive oxygen species formation was observed. Caspase 8 and caspase 9 activities were estimated and AKBA activated the production of caspase 8 and caspase 9 in a dose-dependent pattern. Finally, the cell phase distribution analysis was conducted, and flow cytometric analysis showed that AKBA at 200 μg mL-1 significantly arrest MCF-7 cells at the G1 phase and triggered apoptosis.

Boswellia: Systematically scoping the in vitro, in vivo and clinical research

Boswellia is a genus of shrubs or small/medium trees in which there is continued interest in potential medical use of a number of species. This review aimed to produce a ‘map’ of research on Boswellia to identify potential for translation of research findings across different areas and any research gaps. Searches were carried out using major databases for in vitro, in vivo and clinical studies on any condition or disease, involving Boswellia species and extracts. Data were extracted on the health condition or disease, study type, Boswellia species and form being investigated. 5296 records were retrieved resulting in 657 relevant research papers; 297 (45.2%) reported in vitro studies, 236 (40.0%) reported in vivo studies, and 68 (10.3%) reported clinical studies . Studies were located corresponding to 20 of 22 health research categories, the most frequently researched being Cancer and Neoplasms, Inflammatory and Immune System, and Infection. The species Boswellia serrata and Boswellia sacra have undergone most investigation. Different forms of Boswellia were employed with boswellic acids, specifically Acetyl-11-keto-β-Boswellic acid (AKBA) and 11-Keto-β-Boswellic acid (KBA) generating most interest. Significant numbers of animal studies were located but few clinical studies. The extent, range and nature of the research on extracts and products derived from Boswellia species is revealed. Research is highlighted which may have more widely applicable results (for example on pharmacokinetics, delivery and toxicity), as are current research gaps and potential targets for greater collation of existing data to reduce duplication.

Acetyl-11-keto-β-boswellic acid improves clinical symptoms through modulation of Nrf2 and NF-κB pathways in SJL/J mouse model of experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is characterized by chronic autoimmune inflammation of central nervous system (CNS), i.e. brain and spinal cord. Autoimmune inflammation of the CNS and periphery causes demyelination of axons ultimately leading to clinical symptoms such as gait imbalance, lack of coordination and paraplegia. Innate immune cells such as dendritic cells and neutrophils play a critical role in the initiation and progression of MS through upregulation of oxidants. Two prominent pathways that play important role in regulation of oxidant-antioxidant balance are nuclear factor-erythroid factor 2-related factor 2(Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Nrf2-mediated upregulation of antioxidants counteracts NF-κB-mediated oxidant generation. Therefore, this study evaluated the effects of nutraceutical drug, acetyl-11-keto-β-boswellic acid (AKBA) in relapsing remitting model of experimental autoimmune encephelomyelitis (EAE). Efficacy of AKBA was explored on clinical symptoms, Nrf2, hemeoxygenase-1 (HO-1), NF-κB, inducible nitric oxide synthase (iNOS) in CNS and periphery of SJL/J mice. Our results show that expression of p-NF-κB and iNOS is elevated, whereas expression of Nrf2 and HO-1 is decreased in CD11c + DCs and CNS, which is linked with appearance of clinical symptoms in immunized SJL/J mice. Treatment of immunized SJL/J mice with AKBA causes improvement of clinical symptoms and downregulation of inflammatory markers in CD11c + DCs (p-NF-κB, iNOS, and nitrotyrosine), and CNS (p-NF-κB, iNOS, nitrotyrosine,lipid peroxides, and total antioxidant capacity). Treatment of immunized SJL/J mice with AKBA also causes rectification of Nrf2 signaling in CD11c + DCs, and CNS. These results propose AKBA ameliorates EAE disease progression through rectification of Nrf2 signaling and attenuation of NF-κB pathway in RR model of EAE. Therefore, nutraceutical compound, AKBA may be therapeutically useful in RRMS.

Synthesis of 3-O-Acetyl-11-keto-β-boswellic Acid (AKBA)-Derived Amides and Their Mitochondria-Targeted Antitumor Activities

In this study, we synthesized a series of amide and mitochondria-targeted derivatives with 3-O-acetyl-11-keto-β-boswellic acid (AKBA) as the parent structure and an ethylenediamine moiety as the link chain. Compound 5e, a mitochondrial-targeting potential derivative, showed significantly stronger antitumor activity than that of AKBA, and it could induce vacuolization of A549 cells and stimulate the production of reactive oxygen species (ROS) in a time- and concentration-dependent manner. The antioxidant N-acetylcysteine (NAC) could inhibit the ROS level but could not suppress vacuolization and cell death induced by 5e. Further studies demonstrated that 5e caused abnormal opening of mitochondrial permeability transition pore (MPTP) and a decrease of mitochondrial membrane potential; additionally, it caused cell cycle arrest in G0/G1 but did not induce apoptosis. 5e represented a compound with improved antiproliferative effects for cancer therapy working through new mechanisms.

The protective effect of Boswellic acid and Ellagic acid loaded, colon targeted, and pH-sensitive N-succinyl chitosan in ulcerative colitis rat model

Targeted drug delivery systems that provide therapeutic activity with lower concentrations of both herbal and other substances, while reducing access to non-target sites and undesirable effects; have an important potential for future projections in terms of pharmacological and toxicological studies. The present study aimed to investigate the protective effects of Acetyl 11-keto-β-boswellic acid (AKBA) and Ellagic acid (EA) loaded, colon targeted, and pH-Sensitive N-succinyl chitosans (NsCh) in ulcerative colitis (UC) model induced by acetic acid (AA) in rats. The physicochemical characterization (elemental analysis, FT-IR, DSC, XRD, SEM, NMR) analyses, swelling, and releasing tests of NsCh's suggested that AKBA and EA were successfully loaded to pH-sensitive polymer and targeted to the colon. The targeted AKBA and EA were administered to Wistar rats (n:30, 5 groups) and damage, inflammatory cytokine, protein expression, oxidative stress, and antioxidant parameter levels in colon tissues of the groups were determined. Increase in the levels of CAT, GPx activities, and decrease in necrosis, inflammation, and levels of MDA, TNF-α, COX-2, NF-kB were observed in the targeted EA and AKBA groups compared to the UC group. The potential protective effect of EA and AKBA loaded, colon-targeted, pH-sensitive controlled releasing system against UC and the potential to be licensed preparations by completing the next stages of in vitro and in vivo studies were demonstrated.

Binding of boswellic acids to functional proteins of the SARS-CoV-2 virus: Bioinformatic studies.

Boswellic acids (BAs) have been shown to possess antiviral activity. Using bioinformatic methods, it was tested whether or not acetyl‐11‐keto‐β‐boswellic acid (AKBA), 11‐keto‐β‐boswellic acid (KBA), β‐boswellic acid (BBA), and the phosphorylated active metabolite of Remdesivir® (RGS‐P3) bind to functional proteins of SARS‐CoV‐2, that is, the replicase polyprotein P0DTD1, the spike glycoprotein P0DTC2, and the nucleoprotein P0DTC9. Using P0DTD1, AKBA and KBA showed micromolar binding affinity to the RNA‐dependent RNA polymerase (RdRp) and to the main proteinase complex Mpro. Phosphorylated BAs even bond in the nanomolar range. Due to their positive and negative charges, BAs and RGS‐P3 bond to corresponding negative and positive areas of the protein. BAs and RGS‐P3 docked in the tunnel‐like cavity of RdRp. BAs also docked into the elongated surface rim of viral Mpro. In both cases, binding occurred with active site amino acids in the lower micromolecular to upper nanomolar range. KBA, BBA, and RGS‐P3 also bond to P0DTC2 and P0DTC9. The binding energies for BAs were in the range of −5.8 to −6.3 kcal/mol. RGS‐P3 and BAs occluded the centrally located pore of the donut‐like protein structure of P0DTC9 and, in the case of P0DTC2, RGS‐P3 and BAs impacted the double‐wing‐like protein structure. The data of this bioinformatics study clearly show that BAs bind to three functional proteins of the SARS‐CoV‐2 virus responsible for adhesion and replication, as does RGS‐P3, a drug on the market to treat this disease. The binding effectiveness of BAs can be increased through phosphate esterification. Whether or not BAs are druggable against the SARS‐CoV‐2 disease remains to be established.

Inhibitory effect of acetyl-11-keto-β-boswellic acid on titanium particle-induced bone loss by abrogating osteoclast formation and downregulating the ERK signaling pathway

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.

Role of Testosterone Levels on the Combinatorial Effect of Boswellia serrata Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells.

Co-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. However, the whole extract of the gum resin Boswellia serrata (BS) and anti-androgen enzalutamide has not been explored in prostate cancer to date. We hypothesized that the BS extract containing 30% (AKBA) with enzalutamide acted synergistically in the early phase of cancer, especially in LNCaP cells, by inhibiting androgen receptor (AR) and by reducing cell proliferation, and further, that the extract would be superior to the action of the active ingredient AKBA when used alone or in combination with enzalutamide. To test our hypothesis, we treated LNCaP cells with BS extract or AKBA and enzalutamide both individually and in combination to analyze cell viability under different levels of dihydrotestosterone (DHT). The inhibition of androgen receptor (AR) followed by the expression of prostate-specific antigen (PSA) and the efflux mechanism of the cells were analyzed to determine the effect of the combination on the cellular mechanism. Cells derived from prostate cancer patients were also tested with the combination. Only 6 µM enzalutamide along with BS in the range of 4.1 µg/ml to 16.4 µg/ml gave the best synergistic results with nearly 50% cell killing even though standard enzalutamide doses were as high as 48 µM. Cell killing was most effective at intermediate DHT concentrations of approximately 1 nM, which corresponds to normal physiological serum levels of DHT. The Pgp expression level and the androgen receptor expression levels were reduced under the combination treatment; the former helping to minimize drug efflux and the latter by reducing the sensitivity to hormonal changes. Furthermore, the combination reduced the PSA level secreted by the cells. In contrast, AKBA could not achieve the needed synergism for adequate cell killing at equivalent concentrations. The combination of enzalutamide and BS extract containing 30% AKBA because of their synergistic interaction is an attractive therapeutic option for treating early stage (hormone-dependent) prostate cancer and is superior to the use of AKBA alone.