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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. [ABSTRACT FROM AUTHOR]

Bacterial nanocellulose has been widely investigated in drug delivery, but the incorporation of lipophilic drugs and controlling release kinetics still remain a challenge. The inclusion of polymer particles to encapsulate drugs could address both problems but is reported sparely. In the present study, a formulation approach based on in situ precipitation of poly(lactic-co-glycolic acid) within bacterial nanocellulose was developed using and comparing the conventional solvent N-methyl-2-pyrrolidone and the alternative solvents poly(ethylene glycol), CyreneTM and ethyl lactate. Using the best-performing solvents N-methyl-2-pyrrolidone and ethyl lactate, their fast diffusion during phase inversion led to the formation of homogenously distributed polymer microparticles with average diameters between 2.0 and 6.6 µm within the cellulose matrix. Despite polymer inclusion, the water absorption value of the material still remained at ~50% of the original value and the material was able to release 32 g/100 cm2 of the bound water. Mechanical characteristics were not impaired compared to the native material. The process was suitable for encapsulating the highly lipophilic drugs cannabidiol and 3-O-acetyl-11-keto-β-boswellic acid and enabled their sustained release with zero order kinetics over up to 10 days. Conclusively, controlled drug release for highly lipophilic compounds within bacterial nanocellulose could be achieved using sustainable solvents for preparation. [ABSTRACT FROM AUTHOR]

Inflammation is an integral part of autoimmune diseases, which are caused by dysregulation of the immune system. This dysregulation involves an imbalance between pro-inflammatory versus anti-inflammatory mediators. These mediators include various cytokines and chemokines; defined subsets of T helper/T regulatory cells, M1/M2 macrophages, activating/tolerogenic dendritic cells, and antibody-producing/regulatory B cells. Despite the availability of many anti-inflammatory/immunomodulatory drugs, the severe adverse reactions associated with their long-term use and often their high costs are impediments in effectively controlling the disease process. Accordingly, suitable alternatives are being sought for these conventional drugs. Natural products offer promising adjuncts/alternatives in this regard. The availability of specific compounds isolated from dietary/medicinal plant extracts have permitted rigorous studies on their disease-modulating activities and the mechanisms involved therein. Here, we describe the basic characteristics, mechanisms of action, and preventive/therapeutic applications of 5 well-characterized natural product compounds (Resveratrol, Curcumin, Boswellic acids, Epigallocatechin-3-gallate, and Triptolide). These compounds have been tested extensively in animal models of autoimmunity as well as in limited clinical trials in patients having the corresponding diseases. We have focused our description on predominantly T cell-mediated diseases, such as rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, ulcerative colitis, and psoriasis. [ABSTRACT FROM AUTHOR]

Boswellia sacra oleo gum resin (Burseraceae) commonly known as frankincense is traditionally used in many countries for its beneficial effect on male fertility. This study explores its effect on the male reproductive system after a 60-day repeated administration at two different doses to rats (in vivo) and on human Leydig cells (in vitro). The methanolic extract of B. sacra was analyzed for the presence of various constituents by preliminary phytochemical analysis and gas chromatography-mass spectrometry (GC-MS) while quantitative analysis of boswellic acids was done by high-performance liquid chromatography (HPLC). Administration of B. sacra extract to rats elevated the serum testosterone levels with an associated reduction in serum levels of FSH and LH. An increase in the activity of antioxidant enzymes, superoxide dismutase and catalase, was seen. A dose-dependent increase in the sperm count and sperm motility was also observed. The in vivo results were supported by changes in the expression of the Bcl-2 gene and caspase-3 gene in human Leydig cells in vitro. The results of this study support the traditional use of B. sacra to increase male fertility. [ABSTRACT FROM AUTHOR]

Boswellic acids (BAs) are the main bioactive compounds of frankincense, a natural resin obtained from the genus Boswellia. This study aimed to develop a self-nanoemulsifying delivery system (SNEDS) to improve the antimicrobial and antiproliferative activities of standardized frankincense extract (Fr-extract). Fr-extract was standardized, and BA content was quantified using the developed HPLC-UV method. Screening studies of excipients followed by formula optimization using a mixture simplex lattice design was employed. The optimized Fr-SENDS formulation was characterized. Furthermore, microbiological and antiproliferative assessments of the standardized Fr-extract and Fr-SNEDS were evaluated. Quantification demonstrated that the major constituent is 11-keto-boswellic acid (KBA) (16.25%) among BA content (44.96%). The optimized Fr-SENDS (composed of 5% CapryolTM 90, 48.7% Gelucire® 44/14 and 46.3% ethanol) showed spherical nanosized dispersions with DS, PDI, and zeta potential of 17.9 nm, 0.2, and -14.5 mV, respectively. Fr-SNEDS exhibited lower MIC and MBC values compared with Fr-extract against pathogens conjugated with lung cancer and was comparable to reference antimicrobials. Fr-SNEDS showed superior antiproliferative activity over Fr-extract, with IC50 values of 20.49 and 109.5 μg mL-1, respectively. In conclusion, the optimized Fr-SNEDS could be easily developed and manufactured at a low cost and the in vitro results support its use as a potential adjuvant oral therapy for lung cancer. Further in vivo studies could be continued to assess the therapeutic efficiency of the prepared system. [ABSTRACT FROM AUTHOR]

Boswellia serrata and Boswellia sacra (syn. B. carteri) are important medicinal plants widely used for their content of bioactive lipophilic triterpenes. The qualitative and quantitative determination of boswellic acids (BAs) is important for their use in dietary supplements aimed to provide a support for osteoarthritic and inflammatory diseases. We used High Performance Liquid Chromatography (HPLC)-Diode Array Detector (DAD) coupled to ElectroSpray Ionization and tandem Mass Spectrometry (ESI-MS/MS) for the qualitative and quantitative determination of BAs extracted from the gum resins of B. sacra and B. serrata. Limit of detection (LOD), limit of quantification (LOQ), and Matrix Effect were assessed in order to validate quantitative data. Here we show that the BAs quantitative determination was 491.20 g·kg-1 d. wt (49%) in B. sacra and 295.25 g·kg-1 d. wt (30%) in B. serrata. Lower percentages of BAs content were obtained when BAs were expressed on the gum resin weight (29% and 16% for B. sacra and B. serrata, respectively). The content of Acetyl-11-Keto-β-Boswellic Acid (AKBA) was higher in B. sacra (70.81 g·kg-1 d. wt; 7%) than in B. serrata (7.35 g·kg-1 d. wt; 0.7%). Our results show that any claim of BAs content in either B. sacra or B. serrata gum resins equal to or higher than 70% or AKBA contents of 30% are simply unrealistic or based on a wrong quantitative determination. [ABSTRACT FROM AUTHOR]

Inflammation is an integral part of autoimmune diseases, which are caused by dysregulation of the immune system. This dysregulation involves an imbalance between pro-inflammatory versus anti-inflammatory mediators. These mediators include various cytokines and chemokines; defined subsets of T helper/T regulatory cells, M1/M2 macrophages, activating/tolerogenic dendritic cells, and antibody-producing/regulatory B cells. Despite the availability of many anti-inflammatory/immunomodulatory drugs, the severe adverse reactions associated with their long-term use and often their high costs are impediments in effectively controlling the disease process. Accordingly, suitable alternatives are being sought for these conventional drugs. Natural products offer promising adjuncts/alternatives in this regard. The availability of specific compounds isolated from dietary/medicinal plant extracts have permitted rigorous studies on their disease-modulating activities and the mechanisms involved therein. Here, we describe the basic characteristics, mechanisms of action, and preventive/therapeutic applications of 5 well-characterized natural product compounds (Resveratrol, Curcumin, Boswellic acids, Epigallocatechin-3-gallate, and Triptolide). These compounds have been tested extensively in animal models of autoimmunity as well as in limited clinical trials in patients having the corresponding diseases. We have focused our description on predominantly T cell-mediated diseases, such as rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, ulcerative colitis, and psoriasis.

Extracts of frankincense, the gum resin of Boswellia species, have been extensively used in traditional folk medicine since ancient times and are still of great interest as promising anti-inflammatory remedies in Western countries. Despite their common therapeutic use and the intensive pharmacological research including studies on active ingredients, modes of action, bioavailability, pharmacokinetics, and clinical efficacy, frankincense preparations are available as nutraceuticals but have not yet approved as a drug on the market. A major issue of commercially available frankincense nutraceuticals is the striking differences in their composition and quality, especially related to the content of boswellic acids (BAs) as active ingredients, mainly due to the use of material from divergent Boswellia species but also because of different work-up and extraction procedures. Here, we assessed three frequently used frankincense-based preparations for their BA content and the interference with prominent pro-inflammatory actions and targets that have been proposed, that is, 5-lipoxygenase and leukotriene formation in human neutrophils, microsomal prostaglandin E2 synthase-1, and inflammatory cytokine secretion in human blood monocytes. Our data reveal striking differences in the pharmacological efficiencies of these preparations in inflammation-related bioassays which obviously correlate with the amounts of BAs they contain. In summary, high-quality frankincense extracts display powerful anti-inflammatory effectiveness against multiple targets which can be traced back to BAs as bioactive ingredients. [ABSTRACT FROM AUTHOR]

In continuation of our search for leads from medicinal plants against protozoal pathogens, we detected antileishmanial activity in polar fractions of a dichloromethane extract from Boswellia serrata resin. 11-keto-β-boswellic acid (KBA) could be isolated from these fractions and was tested in vitro against Leishmania donovani axenic amastigotes along with five further boswellic acid derivatives. 3-O-acetyl-11-keto-β-boswellic acid (AKBA) showed the strongest activity with an IC50 value of 0.88 µM against axenic amastigotes but was inactive against intracellular amastigotes in murine macrophages [ABSTRACT FROM AUTHOR]

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]