Effectiveness of gellan gum scaffolds loaded with Boswellia serrata extract for in-situ modulation of pro-inflammatory pathways affecting cartilage healing.

In this study, we developed a composite hydrogel based on Gellan gum containing Boswellia serrata extract (BSE). BSE was either incorporated directly or loaded into an MgAl-layered double hydroxide (LDH) clay to create a multifunctional cartilage substitute. This composite was designed to provide anti-inflammatory properties while enhancing chondrogenesis. Additionally, LDH was exploited to facilitate the loading of hydrophobic BSE components and to improve the hydrogel's mechanical properties. A calcination process was also adopted on LDH to increase BSE loading. Physicochemical and mechanical characterizations were performed by spectroscopic (XPS and FTIR), thermogravimetric, rheological, compression test, weight loss and morphological (SEM) investigations. RPLC-ESI-FTMS was employed to investigate the boswellic acids release in simulated synovial fluid. The composites were cytocompatible and capable of supporting the mesenchymal stem cells (hMSC) growth in a 3D-conformation. Loading BSE resulted in the modulation of the pro-inflammatory cascade by down-regulating COX2, PGE2 and IL1ß. Chondrogenesis studies demonstrated an enhanced differentiation, leading to the up-regulation of COL 2 and ACAN. This effect was attributed to the efficacy of BSE in reducing the inflammation through PGE2 down-regulation and IL10 up-regulation. Proteomics studies confirmed gene expression findings by revealing an anti-inflammatory protein signature during chondrogenesis of the cells cultivated onto loaded specimens. Concluding, BSE-loaded composites hold promise as a tool for the in-situ modulation of the inflammatory cascade while preserving cartilage healing.

Boswellia serrata Enhances Passive Range-of-Motion Exercises in Radiation-Induced Trismus: A Case Report.

Trismus is a common, extremely detrimental side effect following definitive radiotherapy for head and neck malignancies. Existing therapeutic modalities (active and passive range-of-motion exercises and systemic therapies) offer only modest, slow improvements in jaw opening; thus, there is a need for additional treatment options. Boswellia serrata (BS) ("Indian frankincense") is a tree native to West Asia and North Africa that produces resin-containing "boswellic" acids. These have been shown to have in vitro and in vivo anti-inflammatory effects and have previously been found to be an effective treatment for asthma, colitis, arthritis, and post-radiation edema. Herein we report the case of a 54-year-old male with severe post-radiation trismus who experienced a dramatic resolution with BS/Therabite® combination therapy. His trismus improved from 6 mm to 45 mm over 10 weeks (0.46 mm/day), far exceeding previous rates of improvement documented in the literature. There were no ill effects. Given the dearth of effective treatments for post-radiation trismus, BS is a promising agent deserving of further study.

Osteoarthritis: Insights into Diagnosis, Pathophysiology, Therapeutic Avenues, and the Potential of Natural Extracts.

Osteoarthritis (OA) stands as a prevalent and progressively debilitating clinical condition globally, impacting joint structures and leading to their gradual deterioration through inflammatory mechanisms. While both non-modifiable and modifiable factors contribute to its onset, numerous aspects of OA pathophysiology remain elusive despite considerable research strides. Presently, diagnosis heavily relies on clinician expertise and meticulous differential diagnosis to exclude other joint-affecting conditions. Therapeutic approaches for OA predominantly focus on patient education for self-management alongside tailored exercise regimens, often complemented by various pharmacological interventions primarily targeting pain alleviation. However, pharmacological treatments typically exhibit short-term efficacy and local and/or systemic side effects, with prosthetic surgery being the ultimate resolution in severe cases. Thus, exploring the potential integration or substitution of conventional drug therapies with natural compounds and extracts emerges as a promising frontier in enhancing OA management. These alternatives offer improved safety profiles and possess the potential to target specific dysregulated pathways implicated in OA pathogenesis, thereby presenting a holistic approach to address the condition's complexities.

Frankincense (Boswellia serrata) Extract Effects on Growth and Biofilm Formation of Porphyromonas gingivalis, and Its Intracellular Infection in Human Gingival Epithelial Cells.

Frankincense is produced by Boswellia trees, which can be found throughout the Middle East and parts of Africa and Asia. Boswellia serrata extract has been shown to have anti-cancer, anti-inflammatory, and antimicrobial effects. Periodontitis is an oral chronic inflammatory disease that affects nearly half of the US population. We investigated the antimicrobial effects of B. serrata extract on two oral pathogens associated with periodontitis. Using the minimum inhibitory concentration and crystal violet staining methods, we demonstrated that Porphyromonas gingivalis growth and biofilm formation were impaired by treatment with B. serrata extracts. However, the effects on Fusobacterium nucleatum growth and biofilm formation were not significant. Using quantification of colony-forming units and microscopy techniques, we also showed that concentrations of B. serrata that were not toxic for host cells decreased intracellular P. gingivalis infection in human gingival epithelial cells. Our results show antimicrobial activity of a natural product extracted from Boswellia trees (B. serrata) against periodontopathogens. Thus, B. serrata has the potential for preventing and/or treating periodontal diseases. Future studies will identify the molecular components of B. serrata extracts responsible for the beneficial effects.

Evaluating the Anti-Osteoarthritis Potential of Standardized Boswellia serrata Gum Resin Extract in Alleviating Knee Joint Pathology and Inflammation in Osteoarthritis-Induced Models.

Osteoarthritis is a widespread chronic degenerative disease marked by the deterioration of articular cartilage, modifications in subchondral bone, and a spectrum of symptoms, including pain, stiffness, and disability. Ultimately, this condition impairs the patient's quality of life. This study aimed to evaluate the therapeutic efficacy of standardized Boswellia serrata gum resin extract (BSRE) in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. A total of 60 rats were allocated into six groups: normal control group (NC), osteoarthritis control (injected with MIA, OC), O + B50 (injected with MIA and treated with 50 mg/kg body weight (BW) BSRE), O + B75 (injected with MIA and treated with 75 mg/kg BW BSRE), O + B100 (injected with MIA and treated with 100 mg/kg BW BSRE), and O + M (injected with MIA and treated with 150 mg/kg BW methyl sulfonyl methane). Several parameters, including knee joint swelling, histopathological changes, and the expression of collagen type II alpha 1 (COL2A1) and aggrecan, were comprehensively assessed. Concurrently, the serum levels and mRNA expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) were analyzed in both the serum and knee joint synovium. The results demonstrated that BSRE significantly mitigated knee joint swelling, cartilage destruction, and tissue deformation. Notably, BSRE administration markedly upregulated the expression of COL2A1 and aggrecan while concurrently reducing levels of nitric oxide, prostaglandin E2, leukotriene B4, interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Furthermore, a substantial decrease was observed in the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-6, TNF-α and MMP-3 and -13, thereby indicating promising therapeutic implications for osteoarthritis. In conclusion, BSRE exhibited anti-inflammatory properties and inhibited cartilage matrix degradation in a rat model of MIA-induced osteoarthritis, with the O + B100 group showing significant reductions in swelling and notable improvements in joint cartilage damage. These findings illuminate the preventive and therapeutic potential of BSRE for osteoarthritis treatment, emphasizing the criticality of exhaustive evaluation of novel compounds.

Anti-proliferative, Pro-apoptotic, and Chemosensitizing Potential of 3-Acetyl-11-keto-ß-boswellic Acid (AKBA) Against Prostate Cancer Cells.

Prostate cancer incidences are rising worldwide at an alarming rate. Drug resistance and relapse are two major challenges in the treatment of prostate cancer. Therefore, new multimodal, safe, and effective therapeutic agents are urgently required which could effectively mitigate the menace of tumor recurrence and chemo-resistance. Plant-derived products are increasingly being utilized due to their antioxidant, antibacterial, and anti-tumor potential. In the current study, 3-acetyl-11-keto-ß-boswellic acid, a triterpenoid isolated from plant Boswellia, was utilized to ascertain its chemotherapeutic potential against human prostate cancer cells. Various in vitro assays including cell viability, nuclear staining, mitochondria potential, reactive oxygen species (ROS) generation, and quantification of apoptosis, were performed for the evaluation of the cytotoxic potential of AKBA. We observed that AKBA (10-50 µM) dose-dependently suppressed cell proliferation and caused programmed cell death in PC3 cells via both intrinsic and extrinsic pathway. Intriguingly, AKBA was also found to chemosensitize PC3 cells in synergistic combination with doxorubicin. To the best of our knowledge, this is the first study to document the synergistic chemosensitizing impact of AKBA when combined with doxorubicin in prostate cancer cells.This showcases the potential of AKBA in combinatorial therapy or adjuvant therapy for the management of prostate cancer. In sum, our results suggested that AKBA is a promising drug-like molecule against prostate cancer. Our investigation introduces a novel perspective, elucidating a previously unexplored dimension, and uncovering a compelling chemosensitizing phenomenon along with a strong synergistic effect arising from the concurrent application of these two agents.

In vitro evaluation of antileishmanial activity of Boswellia serrata essential oil nanoliposome.

BACKGROUND: Leishmaniasis poses a significant health risk. OBJECTIVES: This study aimed to evaluate the effects of Boswellia serrata (B. serrata) essential oil nanoliposomes on Leishmania tropica (L. tropica) in vitro. METHODS: A mixture of B. serrata essential oil, phosphatidylcholine and Tween 80 were used to prepare B. serrata essential oil nanoliposomes, followed by drying, hydration and size characterisation. The promastigotes of L. tropica were cultured in Roswell Park Memorial Institute medium (RPMI-1640) containing streptomycin, penicillin and fetal bovine serum. Different concentrations of B. serrata essential and nanoliposomes were tested for their antileishmanial properties by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide tests (MTT). RESULTS: Results of Dynamic Light Scattering (DLS) for B. serrata nanoliposomes indicate that they are successful at producing nanoliposomes with dimensions of 74.8 nm. At 1 µg/mL dose, B. serrata essence caused 17 ± 1.73% mortality, while B. serrata nanoliposomes induced 26 ± 1.15% mortality. B. serrata essence achieved a mortality of 55 ± 2.88% at 10 µg/mL, whereas B. serrata nanoliposomes demonstrated a mortality of 63.66±0.88% at 10 µg/mL. Furthermore, there was a significant difference between similar concentrations of B. serrata and B. serrata nanoliposomes. The LC50 of B. serrata essential oil is 7.26 µg/mL in the 95% confidence interval (12.13-5.25). The LC90 value of B. serrata essential oil is 129.37 µg/mL in the 95% confidence interval (50.07-852.58). The LC50 value of B. serrata nanoliposome is 4.20 µg/mL in the 95% confidence interval (6.13-3.10). LC90 value for B. serrata nanoliposome is calculated as 91.89 µg/mL in the 95% confidence interval (37.09-583.29). CONCLUSIONS: In vitro experiments have shown that B. serrata oil and the nanoliposome suppress the proliferation of L. tropica promastigotes, which suggests it may be a promising option for treating leishmaniasis.

Efficacy evaluation of standardized Boswellia serrata extract (AflapinⓇ) in osteoarthritis: A systematic review and sub-group meta-analysis study.

BACKGROUND AND PURPOSE: Osteoarthritis (OA) is a joint disease characterized by pain, inflammation, and physical disability. Boswellia serrata (BS) is widely studied for its effectiveness in OA condition. Our systematic review and meta-analysis study was aimed to evaluate BS extract efficacy in OA. A sub-group analysis was performed to compare the efficacy of a standardized BS extract (AflapinⓇ) with other BS extracts. METHODS: Randomized controlled trials, identified from three online databases, evaluating the effect of BS extracts in OA were included. Quality of studies was assessed using PEDro scale and risk of bias was assessed using Cochrane Risk of Bias tool. Pooled effect was reported as mean difference (MD) and 95% confidence interval. Study was conducted as per the Cochrane guidelines (PROSPERO registration ID: CRD42023411356). RESULTS: Nine RCTs with 712 participants were included. All studies (except one) were good quality studies. BS supplementation significantly reduced VAS (MD: -10.71; p<0.00001), LFI (MD: -2.99; p<0.00001), WOMAC-pain (MD: -10.69; p<0.0001), WOMAC-stiffness (MD: -5.49; p<0.00001), and WOMAC-function (MD: -10.69; p<0.00001) scores compared to control therapy. By sub-group analysis, AflapinⓇ supplementation showed greater reduction in VAS (MD: -16.09 vs -4.68), LFI (MD: -3.81 vs -2.01), WOMAC-pain (MD: -18.68 vs -7.07), WOMAC-stiffness (MD: -14.25 vs -3.78), and WOMAC-function (MD: -14.99 vs -8.41) scores as compared to other BS therapies. CONCLUSIONS: BS supplementation is effective OA symptomatic management. Sub-group analysis revealed that AflapinⓇ supplementation may be better in improving the symptoms of OA which needs to be confirmed by more comparative clinical studies.

The anti-proliferative effects of a frankincense extract in a window of opportunity phase ia clinical trial for patients with breast cancer.

PURPOSE: Boswellic acids, active components of frankincense, suppress tumor proliferation in vitro with a strong clinical trial safety profile in patients with inflammatory diseases. We performed a Phase Ia window of opportunity trial of Boswellia serrata (B. serrata) in patients with breast cancer to evaluate its biologic activity and safety. METHODS: Patients with invasive breast cancer were treated pre-operatively with B. Serrata (2400 mg/day PO) until the night before surgery for a median of 11 days (SD 6 days; range: 5-23 days). Paraffin-embedded sections from pretreatment diagnostic core biopsies and post-treatment surgical excisions were evaluated using a tunnel assay and immunohistochemistry staining with Ki-67 antibodies. A non-intervention retrospective control arm consisting of core and surgical tissue specimens from untreated patients was used to compare patients treated with B. Serrata. The change in proliferation and apoptosis between diagnostic core specimens and surgical specimens was compared between the control and treatment groups using a two-tailed paired t-test. RESULTS: Twenty-two patients were enrolled, of which 20 received treatment, and 18 had sufficient tissue for IHC. There was an increase in percent change in proliferation from core biopsy to surgical excision in the control group (n = 18) of 54.6 ± 21.4%. In the B. serrata-treated group there was a reduction in proliferation between core biopsy and excision (n = 18) of 13.8 ± 11.7%. This difference was statistically significant between the control and B. serrata-treated groups (p = 0.008). There was no difference in change in apoptosis. There were no serious adverse events related to the drug. CONCLUSION: Boswellia serrata inhibited breast cancer proliferation and was well-tolerated in a Phase Ia window of opportunity trial.

In Silico Exploration of Potential Phytoconstituents from the Bark Extract of Boswellia serrata for Hemorrhoidal Disease: Molecular Docking and Molecular Dynamics Analysis.

Boswellia serrata Roxb. Ex Colebr is a popular medicinal plant used traditionally in herbal medicinal preparations to treat a variety of diseases. The purpose of the present investigation was to investigate the anti-hemorrhoidal property of the bark extract of B. serrata (BS). For this, the sequential Soxhlet extraction method was carried out by using different solvents such as hexane, chloroform, and methanol. After the extraction, the obtained dry extracts were tested for quantitative determinations such as total alkaloid content (TAC), total flavonoid content (TFC), total phenol content (TPC), and total tannin content (TTC) for all the extracts. Moreover, in vitro antioxidant activity was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and scavenging activity against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS). Methanolic bark extract showed the highest TPC (67.10±1.83), TFC (372.73±4.45), TAC (9.732±1.06), and TTC (48.932±1.82), as well as the antioxidant assays DPPH (IC50=9.88 µg/ml) and ABTS (IC50=15.09 µg/ml). In this study, both LC-MS and GC-MS were performed to identify the chemical composition of all the extracts. Consequently, 19 compounds were identified by GC-MS and 27 compounds were identified by LC-MS analysis. The identified phytoconstituent(s) that could potentially interact with the target protein cyclooxygenase-2 (COX-2) (PDB: 4RRW) using molecular dynamics simulation and in silico docking were studied. Three compounds that have passed in drug-likeness and ADME-Tox properties are having more docking score than the standard. In this study, camptothecin, justicidin B, and taxiphyllin are identified as potential lead compounds with anti-hemorrhoidal properties and may be helpful in the process of drug development and discovery of novel drugs. Hence, these results demonstrate that BS is a good source of pharmacologically active components with potential applications against hemorrhoidal disease.

Component Composition and Biological Activity of Oleo-Gum Resin from Boswellia serrata (Burseraceae).

The review summarizes the published data on identification of biologically active compounds (BACs) and the pharmacological potential of various components of oleo-gum resin from the Indian frankincense Boswellia serrata Roxb. ex Colebr. Boswellia oleo-gum resin contains a wide range of BACs from the classes of mono-, sesqui-, di-, and triterpenes. Numerous in vivo and in vitro studies demonstrated their anti-inflammatory and antiproliferative effects. Boswellic acids (BAs), which belong to the tetra- and pentacyclic triterpenoid classes, showed the highest anti-inflammatory activity. The frankincense resin is traditionally used in Ayurvedic and Unani medicine and can provide a promising source to design drugs effective in treating musculoskeletal disorders.

Biosynthesis of MgO Nanoparticles and Their Impact on the Properties of the PVA/Gelatin Nanocomposites for Smart Food Packaging Applications.

Fabricating active and intelligent packaging materials has become the highest demand for catering to market needs, especially after the COVID-19 pandemic, for ensuring food safety. Thus, the wider objective of this article was to promote active and smart packaging biofilms possessing antibacterial and humidity-sensing properties for sustainable poly(vinyl alcohol) (PVA)/gelatin (Ge) reinforced with biosynthesized magnesium nanoparticles (MgO NPs) by a solvent-casting route. The UV-visible spectrum has been utilized to determine the optimized biosynthesized MgO NPs and then the nanostructure of optimized MgO NPs investigated by varying techniques such as XRD, SEM-EDX, TEM, FT-IR, and thermogravimetric analysis. Four MgO NPs proportions (i.e., 1, 3, 5, and 10 wt %) were used to fabricate PVA/Ge biofilms. In the biofilms system, the tensile results showcased that the nanocomposite film containing 5 wt % of MgO NPs had the highest tensile strength value (i.e., 22.10 MPs) compared to the other biofilms or the unfilled blank (i.e., 6.30 MPs). Correspondingly, the humidity-sensing data revealed that the PVA/Ge-1% MgO NPs sensor had higher sensitivity over a broad range of relative humidity from (7-97% RH) and at 100 Hz. Additionally, the hydrophobicity of biofilms, measured by water contact angle, UV-stability, and antioxidant and antibacterial properties was also analyzed to possibly use these biofilms in active food packaging with extended shelf life of foodstuffs. However, the PVA/Ge-1% MgO NPs biofilm was predominately found to possess attractive sensing properties and could be considered as a sensor for intelligent food packaging.

Boswellia serrata Extracts Ameliorates Symptom of Irregularities in Articular Cartilage through Inhibition of Matrix Metalloproteinases Activation and Apoptosis in Monosodium-Iodoacetate-Induced Osteoarthritic Rat Models.

The research examined the effects of Boswellia serrata extracts (BSE) on a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). The severity and progression of MIA-induced osteoarthritis were assessed using microcomputed tomography imaging. Additionally, the study investigated the impact of BSE various the biomarkers associated with osteoarthritis, including anabolic and catabolic factors, pro-inflammatory factors, and apoptosis factors. The evaluation methods employed included western blot, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction analysis in osteoarthritic rats. Supplementing osteoarthritic rats with BSE reduced tissue injury, cartilage destruction, and decreased in MIA-induced roughness on the articular cartilage surface. MIA-treated rats exhibited increased expressions of phosphorylation of Smad3, MMPs, p-IκB, p-NF-κB, and pro-inflammatory factors (IL-1ß, IL-6, TNF-α, and COX-2), which were mitigated by BSE supplementation. Furthermore, protein expressions related to apoptosis pathways were significantly reduced in MIA-induced rats supplemented with BSE. These findings suggested that BSE ingestion may enhance the inflammatory response, decrease JNK-dependent MMPs activation, and alleviate caspase-3-dependent apoptosis in MIA-induced osteoarthritic rat models. Consequently, BSE exhibits potential as a therapeutic agent for treating osteoarthritis.

Efficacy of Boswellia serrata Extract and/or an Omega-3-Based Product for Improving Pain and Function in People Older Than 40 Years with Persistent Knee Pain: A Randomized Double-Blind Controlled Clinical Trial.

A single-center, randomized, double-blind, controlled clinical trial with four arms was conducted in healthy subjects with persistent knee discomfort (pain intensity on 1-10 cm visual analog scale (VAS) > 3) aged 40 years and older treated with a dietary supplement for 8 weeks. The study groups were Boswellia serrata extract (n = 29), an omega-3-based product (AvailOm® 50 High EPA) (n = 31), Boswellia + AvailOm® (n = 30), and placebo (n = 30). The intake of Boswellia + AvailOm® improved the quality of life (QoL) (WOMAC index) and some variables of muscle strength. Statistically significant differences between the AvailOm® and the placebo groups in the decrease of pain intensity were found. Weekly VAS scores showed a significant decrease in pain perception when comparing the AvailOm® product to the placebo, with the lowest VAS scores at week 8. Consumption of Boswellia improved sleep latency. The time to perform the Up and Go test decreased after the intake of AvailOm®. There was an increase in the omega-3 fatty acids, with the greatest increase in the Boswellia + AvailOm® group. AvailOm® was safe and effective in reducing pain and improving the QoL and functionality of subjects over 40 years with persistent knee pain.

Development, Analytical Characterization, and Bioactivity Evaluation of Boswellia serrata Extract-Layered Double Hydroxide Hybrid Composites.

Boswellia serrata Roxb. extract (BSE), rich in boswellic acids, is well known as a potent anti-inflammatory natural drug. However, due to its limited aqueous solubility, BSE inclusion into an appropriate carrier, capable of improving its release in the biological target, would be highly desirable. Starting with this requirement, new hybrid composites based on the inclusion of BSE in a lamellar solid layered double hydroxide (LDH), i.e., magnesium aluminum carbonate, were developed and characterized in the present work. The adopted LDH exhibited a layered crystal structure, comprising positively charged hydroxide layers and interlayers composed of carbonate anions and water molecules; thus, it was expected to embed negatively charged boswellic acids. In the present case, a calcination process was also adopted on the LDH to increase organic acid loading, based on the replacement of the original inorganic anions. An accurate investigation was carried out by TGA, PXRD, FT-IR/ATR, XPS, SEM, and LC-MS to ascertain the nature, interaction, and quantification of the active molecules of the vegetal extract loaded in the developed hybrid materials. As a result, the significant disruption of the original layered structure was observed in the LDH subjected to calcination (LDHc), and this material was able to include a higher amount of organic acids when its composite with BSE was prepared. However, in vitro tests on the composites' bioactivity, expressed in terms of antimicrobial and anti-inflammatory activity, evidenced LDH-BSE as a better material compared to BSE and to LDHc-BSE, thus suggesting that, although the embedded organic acid amount was lower, they could be more available since they were not firmly bound to the clay. The composite was able to significantly decrease the number of viable pathogens such as Escherichia coli and Staphylococcus aureus, as well as the internalization of toxic active species into human cells imposing oxidative stress, in comparison to the BSE.

The Role of Plant-Derived Natural Products in the Management of Inflammatory Bowel Disease-What Is the Clinical Evidence So Far?

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are a major healthcare challenge worldwide. Disturbances in the immune system and gut microbiota followed by environmental triggers are thought to be part of the aetiological factors. Current treatment for IBD includes corticosteroids, immunosuppressants, and other biologic agents; however, some patients are still unresponsive, and these are also linked to high financial load and severe side effects. Plant-derived natural products are rich in phytochemicals and have been used as healing agents in several diseases since antiquity due to their antioxidant, anti-inflammatory, and immunomodulatory properties, as well as gut microbiota modulation. Numerous in vitro and in vivo studies have shown that phytochemicals act in key pathways that are associated with the pathogenesis of IBD. It is also reported that the use of plant-derived natural products as complementary treatments is increasing amongst patients with IBD to avoid the side effects accompanying standard medical treatment. This review summarises the relevant evidence around the use of plant-derived natural products in the management of IBD, with specific focus on the clinical evidence so far for Curcumin, Mastiha, Boswellia serrata, and Artemisia absinthium.

Simultaneous identification and quantification of pentacyclic triterpenoids and phenolic compounds from the leaves of Boswellia serrata using LC-MS/MS tandem mass spectrometry.

Boswellia serrata (B. serrata) is an important medicinal plant widely used as dietary supplements to provide a support for osteoarthritic and inflammatory diseases. The occurrence of triterpenes in leaves of B. serrata is very little or none. Therefore, the qualitative and quantitative determination of phytoconstituents (triterpenes and phenolics) present in the leaves of B. serrata is very much needed. The aim of this study was to develop an easy, rapid, efficient and simultaneous liquid chromatography-mass spectrometry (LC-MS/MS) method for the identification and quantification of the compounds present in the leaves extract of B. serrata. The purification of ethyl acetate extracts of B. serrata was performed by solid phase extraction method, followed by HPLC-ESI-MS/MS analysis. Chromatographic parameters of the analytical method included negative electrospray ionization (ESI-) with a flow of 0.5 mL/min in gradient mode consisting of acetonitrile (A) and water (B) containing 0.1% formic acid, at 20 °C. Total 19 compounds (13 triterpenes and 6 phenolic compounds) were separated, and simultaneously quantified using a validated LC-MS/MS method with high accuracy and sensitivity. Good linearity was obtained with r2 > 0.973 in the calibration range. The overall recoveries were in a range between 95.78 and 100.2% with relative standard deviations (RSD) below 5% for the entire procedure of matrix spiking experiments. Overall, there was no ion suppression from the matrix. The quantification data showed that the total amount of triterpenes and phenolic compounds in the leaves of B. serrata ethyl acetate extract samples ranged from 14.54 to 102.14 mg/g and 2.14 to 93.12 mg/g of dry extract, respectively. This work provides, for the first time, a chromatographic fingerprinting analysis on the leaves of B. serrata. A rapid, efficient, and simultaneous liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and used for the both identification and quantification of triterpenes and phenolic compounds in the leaves extracts of B. serrata. The method established in this work can be used as quality-control method for other market formulations or dietary supplements containing leaf extract of B. serrata.

Boswellia serrata inhibits LPS-induced cardiotoxicity in H9c2 cells: Investigating role of anti-inflammatory and antioxidant effects.

Sepsis-induced myocardial dysfunction is the main reason for mortality and morbidity. Recent investigations have shown that inflammation and oxidative stress play a central role in lipopolysaccharide (LPS)-induced cardiac injury pathophysiology. Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. The present study aimed to investigate the effects of B. serrata pretreatment on LPS-induced cardiac damage in H9c2 cells. The cells were pretreated with various concentrations of B. serrata (5-45 µg/ml) for 24 h and then stimulated with LPS (10 µg/ml) for another 24 h. Afterward, the levels of cell viability, tumor necrosis factor (TNF)-α, prostaglandin (PGE)-2, interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, nitric oxide (NO) and glutathione (GSH) were determined using enzyme-linked immunosorbent assay (ELISA), real time-PCR or appropriated biochemical methods. Our results demonstrated that LPS treatment caused a remarkable decrease in cell viability and GSH, and on the contrary, it led to a significant increase in the levels of gene and protein expression of inflammatory markers and NO. However, pretreatment of B. serrata (5, 15, and 45 µg/ml) decreased the levels of TNF-α, PGE2, IL-1ß, COX-2, iNOS, IL-6, and NO production, while cell viability and GSH levels were increased. Taken together, our results demonstrated that B. serrata might be a potential therapeutic agent against LPS and endotoxemia-induced cardiac injury, through its anti-inflammatory and antioxidant properties.

Evaluation of the effectiveness of topical oily solution containing frankincense extract in the treatment of knee osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Pharmacological treatments of osteoarthritis (OA) have several side effects. Boswellia serrata resin (frankincense) is rich in boswellic acids that have antioxidant and anti-inflammatory effects; though, their oral bioavailability is low. The aim of this study was evaluation of the clinical effectiveness of frankincense extract in the treatment of knee OA. In a randomized double-blind placebo-controlled clinical trial, eligible patients with knee OA were randomly divided into two groups of drug (33 patients) and control (37 patients), to use oily solution of frankincense extract or placebo, respectively, on the involved knee three times daily for four weeks. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), VAS (visual analogue scale; for pain severity), and PGA (patient global assessment) scores were determined before and after intervention. RESULTS: For all evaluated outcome variables, there was a significant decrease from baseline in both groups (P < 0.001 for all). Furthermore, the end-of-intervention values for all parameters were significantly lower in drug group than placebo group (P < 0.001 for all), showing more effectiveness of drug compared to placebo. CONCLUSION: Topical oily solution containing enriched extract of boswellic acids could decrease pain severity and improve the function in patients with knee OA. Trial Registration Trial registration number: IRCT20150721023282N14. Trial registration date: September 20, 2020. The study was retrospectively registered in Iranian Registry of Clinical Trials (IRCT).

Dietary Supplementation with Boswellia serrata, Verbascum thapsus, and Curcuma longa in Show Jumping Horses: Effects on Serum Proteome, Antioxidant Status, and Anti-Inflammatory Gene Expression.

Intense exercise can cause inflammation and oxidative stress due to the production of reactive oxygen species. These pathophysiological processes are interdependent, and each one can induce the other, creating a vicious circle. A placebo-controlled blind study was carried out in show jumping horses (n. 16) to evaluate the effects of a commercial dietary supplement (Dolhorse® N.B.F. Lanes srl, Milan, Italy) containing Verbascum thapsus leaf powder (1.42%), Curcuma longa (14.280 mg/kg), and Boswellia serrata (Roxb ex Colebr) (14.280 mg/kg) extracts. Before and after 10 days of dietary supplementation, blood samples were collected to evaluate the protein levels, antioxidants, and inflammatory responses by proteomic analysis or real-time Reverse Transcriptase-Polymerase Chain Reaction (real-time RT-PCR). A total of 36 protein spots, connected to 29 proteins, were modulated by dietary supplementation, whereas real-time RT-PCR revealed a significant downregulation of proinflammatory cytokines (interleukin 1α (p < 0.05) and interleukin-6 (0.005), toll-like receptor 4 (p < 0.05), and IKBKB (p < 0.05) in supplemented sport horses. Immunoglobulin chains, gelsolin, plasminogen, vitamin D binding protein, apolipoprotein AIV, and filamin B were overexpressed, whereas haptoglobin, α-2-HS-glycoprotein, α2-macroglobulin, afamin, amine oxidase, 60S acidic ribosomal protein, and complement fragments 3, 4, and 7 were reduced. No effect was observed on the antioxidant defense systems. The present results suggest this phytotherapy may reinforce the innate immune responses, thus representing a valid adjuvant to alleviate inflammation, which is a pathophysiological process in sport horses.