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The chemical characterization of natural products is often a complex task that demands powerful analytical techniques. Liquid chromatography with high-resolution tandem mass spectrometry (HRMS/MS) is often employed, yet it can face hard challenges when isomeric species are present, and reference standards are lacking. In such cases, the confidence level in compound identification can be significantly improved by the collection of orthogonal information on target analytes. In this work, 23 key compounds in Boswellia serrata extract (BSE), 12 of which correspond to boswellic acids (BAs) and 11 to triterpenoidic acid isomers, were identified by combining RPLC followed by serial UV and ESI(-)-FTMS and FTMS/MS detections with the evaluation of the reactivity towards C=C bond epoxidation with meta -chloroperoxybenzoic acid ( m -CPBA), proposed as a fast chemical tool to gather information about C=C bond steric hindrance, a key structural feature of BAs and related compounds. The interpretation of UV spectra acquired after chromatographic separation corroborated the identification of the substitution patterns of enonic and dienic residues in ketoboswellic and dehydroboswellic acids. Moreover, MS/MS based on higher-energy collision-induced dissociation (HCD) unveiled new fragmentation pathways, providing important structural details on target analytes. The integrated approach developed during this study might pave the way for a deeper understanding of the BSE bioactive properties. Moreover, it can be considered an example of a more general strategy for the analysis of complex mixtures of natural compounds including also isomeric species.

Background: In the last few decades, it has been largely perceived that the factors affecting the immune system and its varying pathways lead to the pathological progression of inflammation and inflammatory conditions. Chronic inflammation also contributes to common diseases, such as diabetes mellitus, ischemic heart disease, cancer, chronic renal inflammatory disease, non-alcoholic fatty hepat-ic disease, autoimmune diseases and neurodegenerative diseases., Objective: Interestingly, plant sources and secondary metabolites from plants have been increasingly employed in managing acute and chronic inflammatory diseases for centuries. Boswellic acids are pentacyclic triterpenoidal moieties obtained from the oleo gum resin of different Boswellia species., Methods: Detailed data was collected revealing the anti-inflammatory potential of Boswellic acids through various databases., Result: These are pharmacologically active agents that possess promising anti-inflammatory, anti-arthritic, antirheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, and anti-microbial effects., Conclusion: Boswellic acids have been in use since ancient times primarily to treat acute and chronic inflammatory diseases. This review discusses the various mechanisms underlying the inflammatory process and the necessity of such natural products as a medication to treat inflammatory diseases. In addition, a discussion has also been extended to understand the primary targets involved in inflammation. The review further explores the therapeutic potential of boswellic acids in., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The link between diabetes and cognitive dysfunction has been reported in many recent articles. There is currently no disease-modifying treatment available for cognitive impairment. Boswellia serrata (B. serrata) is used traditionally to treat chronic inflammatory diseases such as type 2 diabetes (T2D), insulin resistance (IR), and Alzheimer's disease (AD). This review aims to highlight current research on the potential use of boswellic acids (BAs)/B. serrata extract in T2D and AD. We reviewed the published information through June 2021. Studies have been collected through a search on online electronic databases (Academic libraries as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Accumulating evidence in preclinical and small human clinical studies has indicated that BAs/B. serrata extract has potential therapeutic effect in T2D and AD. According to most of the authors, the potential therapeutic effects of BAs/B. serrata extract in T2D and AD can be attributed to immunomodulatory, anti-inflammatory, antioxidant activity, and elimination of the senescent cells. BAs/B. serrata extract may act by inhibiting the IκB kinase/nuclear transcription factor-κB (IKK/NF-κB) signaling pathway and increasing the formation of selective anti-inflammatory LOX-isoform modulators. In conclusion, BAs/B. serrata extract may have positive therapeutic effects in prevention and therapy of T2D and AD. However, more randomized controlled trials with effective, large populations are needed to show a definitive conclusion about therapeutic efficacy of BAs/B. serrata extract in T2D and AD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Background: The oral administration of the gum resin extracts of Indian frankincense (Boswellia serrata Roxb. ex Colebr) results in very low plasma concentrations of boswellic acids (BAs), being far below the pharmacologically active concentrations required in vitro for anti-inflammatory activity. For that reason the use of Indian frankincense in clinical practice and pharmaceutical development has substantially lagged behind. Recently the application of new formulation technologies resulted in a formulation of frankincense extract with lecithin, which revealed improved absorption and tissue penetration of BAs in a rodent study, leading for the first time to plasma concentrations of BAs in the range of their anti-inflammatory activity., Purpose: In order to verify these encouraging results in humans, the absorption of a standardized Boswellia serrata extract (BE) and its lecithin formulation (CSP) was comparatively investigated in healthy volunteers., Study Design: According to a randomized cross-over design with two treatments, two sequences and two periods, 12 volunteers alternatively received the lecithin-formulated Boswellia extract (CSP) or the non-formulated Boswellia extract (BE) at a dosage of 2×250mg capsules., Methods: The plasma concentrations of the six major BAs (KBA, AKBA, βBA, αBA, AβBA, AαBA) were determined using LC/MS., Results: With the exception of KBA, a significantly higher (both in terms of weight-to-weight and molar comparison) and quicker absorption of BAs from the lecithin formulation was observed, leading to C max in the range required for the interaction with their molecular targets., Conclusion: These findings pave the way to further studies evaluating the clinical potential of BAs, and verify the beneficial effect of lecithin formulation to improve the absorption of poorly soluble phytochemicals., (Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin-induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t1/2, and mean residence time, and decreased the clearance, Vd, markedly as compared with the control group. In rat liver, microsomes BA and AD have shown CYP3A4 inhibitory activity significantly (p < 0.01), compared with the vehicle group. The increase in hypoglycemic action by concomitant administration of glyburide with BA or AD was more in diabetic rats than when the drugs were used singly and with the control group, which suggests the enhancement of glucose reduction capacity of glyburide in diabetic rats along with BA or AD. In PK/PD modeling of BA and AD with glyburide, the predicted PK and PD parameters are in line with the observed PK and PD parameters. The results revealed that BA and AD led to the PK/PD changes because of glyburide-increased bioavailability and because of the inhibition of CYP3A4 enzyme. In conclusion, add-on preparations containing BA or AD may increase the bioavailability of glyburide, and hence the dose should be monitored., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: liver cancer is one of the most common cancers in the world. So far, there is no gold standard treatment for hepatocellular carcinoma. We conducted this in vitro study to assess the effect of three natural products: Boswellic acids, curcumin and naringin versus corresponding nanoparticles (NPs) on Hep G2 cells proliferation. Methods: Boswellic acid, curcumin, naringin-loaded NPs were prepared using nanoprecipitation method. Human liver (HepG2) cell line was cultured in Dulbecco's modified Eagle's medium (DMEM). The cell growth inhibition and cytotoxicity were evaluated by MTT assay. Results: Boswellic acid, curcumin, naringin were able to inhibit HepG2 cells proliferation. IC50 at 24 h, 48 h showed significant lower values in NPs versus Free herbs. IC50 values of free Boswellic acids and NPs at 24 h were (24.60 ± 1.89 and 7.78 ± 0.54, P < 0.001), at 48 h were (22.45 ± 1.13 and 5.58 ± 0.27, P < 0.001) respectively. IC50 values of free curcumin and NPs at 24 h were (5.89 ± 0.8 and 3.46 ± 0.23, P < 0.05), at 48 h were (5.57 ± 0.94 and 2.51 ± 0.11, P < 0.05), respectively. For free and naringenin NPs, IC50 values at 24 h were (14.57 ± 1.78 and 7.25 ± 0.17, P < 0.01), at 48 h were (11.37 ± 1.45 and 5.21 ± 0.18, P < 0.01) respectively. Conclusion: Boswellic acid, curcumin, naringin and their nanoprecipitation prepared nanoparticles suppressed Hep G2 cells proliferation. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a major cause of death and disability. TBI can result in neuropsychiatric and cognitive problems as well as neurodegenerative pathologies that can appear right after or develop and persist years after injury. Method: We conducted a double-blind, randomized, placebo-controlled clinical trial on patients who suffered from TBI three months to three years ago. The patients were randomized to placebo (n = 34) or K-Vie™ group (n = 46) for a treatment period of 3 months. The main primary outcomes include cognitive assessment in the Rey Auditory Verbal Learning Test-Recognition Test (RAVLT), Wechsler adult intelligence Digit Symbol Substitution Test (DSST) and trail-making test part B (TMT-B). Assessments were performed at baseline and at the month 3 follow-up visit. Linear mixed models were carried out to evaluate cognitive changes from baseline across all cognitive assessment tests. Result: The current study showed significant (p < 0.05) improvement in cognitive function of patients who were given K-Vie™ compared with placebo across the RAVLT, DSST and TMT-B performance assessments. A larger cohort would be beneficial to further confirm the clinical utility of K-Vie™ and assess its effects in acute phases of TBI. [ABSTRACT FROM AUTHOR]

Objective: Boswellic acids (BAs) are active constituents of plant Boswellia serrata. In the present study boswellic acids were extracted from Boswellia serrata and dry methanolic extracts were quantified by HPLC and HPTLC. Method: A gradient HPLC method was used for the quantification of the boswellic acids; 11-keto-β-boswellic acid (KBA) and 3- acetyl-11-keto-β-boswellic acid (AKBA). A direct HPTLC assay was developed for the determination of KBA and AKBA at 254 nm. The UV detection of analytical assays were used to examine the purity of KBA and AKBA peaks and compared with the standards. Results: The quantitative results of both analytical methods did not show any major differences between content of KBA and AKBA, although a trend to slightly lower values were found for content of KBA and AKBA in HPLC. The amount of KBA and AKBA in the Boswellia serrata extract was found to be about 3.3% and 4.6% by HPTLC and 3.03% and 3.87% by HPLC respectively. Conslusion: Both methods are simple and effective for quantification of KBA and AKBA in Boswellia serrata extracts and their pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Abstract: Boswellia serrata gum resin extracts (BSE) revealed potent anti-inflammatory actions in preclinical and clinical studies. In 2002 BSE was assigned an orphan drug status by the European Medicines Agency (EMA) for the treatment of peritumoral edema. In the past pharmacological effects of BSE were mainly attributed to 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA). Therefore pharmacokinetic and pharmacodynamic studies focused mainly on these two boswellic acids (BAs). However, other BAs, like β-boswellic acid (βBA), might also contribute to the anti-inflammatory actions of BSE. Here, we determined the metabolic stability, permeability and brain availability of six major BAs, that is, KBA, AKBA, βBA, 3-acetyl-β-boswellic acid (AβBA), α-boswellic acid (αBA), and 3-acetyl-α-boswellic acid (AαBA). For permeability studies, the Caco-2 model was adapted to physiological conditions by the addition of bovine serum albumin (BSA) to the basolateral side and the use of modified fasted state simulated intestinal fluid (FaSSIF) on the apical side. Under these conditions the four BAs lacking the 11-keto moiety revealed moderate permeability. Furthermore the permeability of AKBA and KBA was improved compared to earlier studies. In contrast to Aα- and AβBA, βBA and αBA were intensively metabolized after incubation with human and rat liver microsomes. Finally, the availability of all six major BAs could be confirmed in rat brain 8h after oral administration of 240mg/kg BSE to rats showing mean concentrations of 11.6ng/g for KBA, 37.5ng/g for AKBA, 485.1ng/g for αBA, 1066.6ng/g for βBA, 43.0ng/g for AαBA and 163.7ng/g for AβBA. [Copyright &y& Elsevier]

Medicinal plants represent a big reservoir for discovering new drugs against all kinds of diseases including inflammation. In spite the large number of promising anti-inflammatory plant extracts and isolated components, research on medicinal plants proves to be very difficult. Based on that background this review aims to provide a summarized insight into the hitherto known pharmacologically active concentrations, bioavailability, and clinical efficacy of boswellic acids, curcumin, quercetin and resveratrol. These examples have in common that the achieved plasma concentrations were found to be often far below the determined IC50 values in vitro. On the other hand demonstrated therapeutic effects suggest a necessity of rethinking our pharmacokinetic understanding. In this light this review discusses the value of plasma levels as pharmacokinetic surrogates in comparison to the more informative value of tissue concentrations. Furthermore the need for new methodological approaches is addressed like the application of combinatorial approaches for identifying and pharmacokinetic investigations of active multi-components. Also the physiological relevance of exemplary in vitro assays and absorption studies in cell-line based models is discussed. All these topics should be ideally considered to avoid inaccurate predictions for the efficacy of herbal components in vivo and to unlock the "black box" of herbal mixtures. [ABSTRACT FROM AUTHOR]