holothurin-a and boswellic-acid

Frankincense preparations, used in folk medicine to cure inflammatory diseases, showed anti-inflammatory effectiveness in animal models and clinical trials. Boswellic acids (BAs) constitute major pharmacological principles of frankincense, but their targets and the underlying molecular modes of action are still unclear. Using a BA-affinity Sepharose matrix, a 26-kDa protein was selectively precipitated from human neutrophils and identified as the lysosomal protease cathepsin G (catG) by mass spectrometry (MALDI-TOF) and by immunological analysis. In rigid automated molecular docking experiments BAs tightly bound to the active center of catG, occupying the same part of the binding site as the synthetic catG inhibitor JNJ-10311795 (2-[3-[methyl[1-(2-naphthoyl)piperidin-4-yl]amino]carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid). BAs potently suppressed the proteolytic activity of catG (IC(50) of approximately 600 nM) in a competitive and reversible manner. Related serine proteases were significantly less sensitive against BAs (leukocyte elastase, chymotrypsin, proteinase-3) or not affected (tryptase, chymase). BAs inhibited chemoinvasion but not chemotaxis of challenged neutrophils, and they suppressed Ca(2+) mobilization in human platelets induced by isolated catG or by catG released from activated neutrophils. Finally, oral administration of defined frankincense extracts significantly reduced catG activities in human blood ex vivo vs placebo. In conclusion, we show that catG is a functional and pharmacologically relevant target of BAs, and interference with catG could explain some of the anti-inflammatory properties of frankincense.

Topics: Adult; Amino Acid Sequence; Animals; Anti-Inflammatory Agents, Non-Steroidal; Binding, Competitive; Boswellia; Cathepsin G; Cathepsins; Drug Delivery Systems; Humans; Hydrolysis; Molecular Sequence Data; Plant Extracts; Protein Binding; Serine Endopeptidases; Triterpenes

β-Boswellic acid (β-BA) and 11-keto-β-boswellic acid (β-KBA) are crucial bioactive compounds, mostly isolated from frankincense. These compounds are known for their potent anticancer and anti-inflammatory activities. Herein, we have explored the complete anti-diabetic potential of β-BA and β-KBA with detailed parameters. This research revealed that treatment with β-BA and β-KBA at a dose of 1, 2, and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and specifically the concentration of blood glucose level (BGL) in diabetic animals, which indicated that the β-BA and β-KBA possess strong anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the antioxidant effects. The biochemical analysis revealed that these compounds improve an abnormal level of several biochemical parameters like serum lipid values including total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) to a normal level and the high-density lipoprotein cholesterol level (HDL-C). To understand the mechanism of action of β-BA and β-KBA, their most probable biological targets were searched through the inverse docking approach. Our computational analysis reflects that among other probable targets, the Dipeptidyl peptidase 4 (DPP-4) enzyme could be one of the possible binders of β-BA and β-KBA to produce their anti-diabetic activities. These in-silico results were validated by an in-vitro experiment. It indicates that the anti-diabetic effects of β-BA and β-KBA are produced by the inhibition of DDP-4. Thus, these anti-diabetic, antioxidant, and anti-hyperlipidemic effects of β-BA and β-KBA suggest these compounds as potential therapeutics for diabetic conditions.

Topics: Animals; Blood Glucose; Boswellia; Diabetes Mellitus, Experimental; Dipeptidyl Peptidase 4; Dose-Response Relationship, Drug; Lipids; Malondialdehyde; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley; Streptozocin; Superoxide Dismutase; Triterpenes; Weight Loss

Boswellic acids are the main constituents of Boswellia serrata gum. These comprise of four pentacyclic triterpenes, 11-keto-β-boswellic acid (KBA) being one of them.. Comparing the extraction efficiency of KBA through microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE) followed by optimizing the extraction process using response surface methodology (RSM) and validation of HPTLC.. UAE and MAE of KBA were carried out employing methanol as an extracting solvent. To figure out the better mode of extraction, single factorial experiments were conducted for further optimization. Design expert software was used for optimization purposes where solvent to drug ratio, extraction temperature and extraction time were taken as input variables. Quantification of KBA in each extract was done through High-Performance Thin Layer Chromatography (HPTLC), and the method was validated as per International Council for Harmonization (ICH) guidelines.. UAE stood out to be a better mode of extraction for KBA. Solvent to drug ratio of 20.42 mL/gram, extraction temperature of 44.01°C and extraction time of 11.54 minutes were established as optimum conditions, which yielded 8.44%w/w of KBA. Regarding HPTLC, the Rf value of KBA was measured, and the correlation coefficient was calculated from the standard curve. Accuracy, precision and recovery were found within limits.. From this study, it was concluded that a non-thermal method is a better choice of extraction for KBA. All the input variables significantly affected KBA content, which was confirmed by model fitting. Moreover, the HPTLC method was developed for the quantification of KBA, which was found to be accurate, reliable and highly sensitive.

Topics: Boswellia; Chromatography, Thin Layer; Frankincense; Plant Extracts; Triterpenes

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

Topics: Animals; Cell Line; Humans; Inhibitory Concentration 50; Leishmania donovani; Macrophages; Mice; Plant Extracts; Rats; Resins, Plant; Triterpenes

In the current investigation, a series of heterocyclic derivatives of boswellic acids were prepared along with new monomers of 3-

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dimerization; Female; Humans; Ovarian Neoplasms; Triterpenes

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

Topics: Anti-Inflammatory Agents; Biological Availability; Boswellia; Glycosides; Solubility; Triterpenes; Water

Boswellic acids constitute a group of unique pentacyclic triterpene acids from

Topics: Anti-Inflammatory Agents; Blood Platelets; Boswellia; Calcium; Humans; Plant Extracts; Structure-Activity Relationship; Triterpenes

Huo Luo Xiao Ling Dan (HLXLD), a Chinese herbal formula composed of 11 different herbs, has been used traditionally for the treatment of arthritis and other chronic inflammatory diseases. However, the pharmacokinetic profile of its anti-inflammatory bioactive compounds has not been elucidated. Boswellic acids are the bioactive compounds with potent anti-inflammatory activity isolated from Boswellia serrate which is one of the 11 herbs of HLXLD. The objective of the study was to compare the pharmacokinetics of the two bioactive bowsellic acids: 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic following oral administration of HLXLD or Boswellia serrata extract alone in normal and arthritic rats. An LC-MS method was developed and validated for the determination of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic in the comparative pharmacokinetic study. The results showed that there were significant differences in pharmacokinetic parameters between normal and arthritic groups. Interestingly, the absorptions of two boswellic acids were significantly higher in HLXLD than Boswellia serrata extract alone, indicating the synergistic effect of other herbal ingredients in HLXLD. This comparative pharmacokinetic study provided direct evidence supporting the notion that the efficacy of a complex mixture such as HLXLD is better than that of single components in treating human diseases.

Topics: Animals; Arthritis, Experimental; Boswellia; Chromatography, Liquid; Drug Stability; Drugs, Chinese Herbal; Linear Models; Male; Mass Spectrometry; Plant Extracts; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Triterpenes

Boswellia serrata gum resin extracts are used widely for the treatment of inflammatory diseases. However, very low concentrations in the plasma and brain were observed for the boswellic acids (1-6, the active constituents of B. serrata). The present study investigated the effect of phospholipids alone and in combination with common co-surfactants (e.g., Tween 80, vitamin E-TPGS, pluronic f127) on the solubility of 1-6 in physiologically relevant media and on the permeability in the Caco-2 cell model. Because of the high lipophilicity of 1-6, the permeability experiments were adapted to physiological conditions using modified fasted state simulated intestinal fluid as apical (donor) medium and 4% bovine serum albumin in the basolateral (receiver) compartment. A formulation composed of extract/phospholipid/pluronic f127 (1:1:1 w/w/w) increased the solubility of 1-6 up to 54 times compared with the nonformulated extract and exhibited the highest mass net flux in the permeability tests. The oral administration of this formulation to rats (240 mg/kg) resulted in 26 and 14 times higher plasma levels for 11-keto-β-boswellic acid (1) and acetyl-11-keto-β-boswellic acid (2), respectively. In the brain, five times higher levels for 2 compared to the nonformulated extract were determined 8 h after oral administration.

Topics: Absorption; Administration, Oral; Animals; Boswellia; Brain; Caco-2 Cells; Humans; Male; Models, Biological; Permeability; Phospholipids; Poloxamer; Polysorbates; Rats; Solubility; Time Factors; Triterpenes; Vitamin E

Semi-synthetic analogues of β-boswellic acid (BA) and 11-keto-β-boswellic acid (KBA) were comparatively evaluated for in vitro cytotoxicity against human myeloid leukaemia (HL-60) and human cervical carcinoma (HeLa) cells. 2-Cyano analogues of both the triterpenes were observed to have significant cytotoxicity against both the cells, displaying cytotoxicity in HL-60 cells at low concentrations. Further investigations suggested the proapoptotic potential associated with the two molecules to induce cytotoxicity in HL-60 cells, where one of them showed early proapoptotic effect as evidenced by several biological end-points of the apoptosis such as annexinV binding, DNA fragmentation and increase in sub-G0 DNA fraction and apoptotic bodies formation (Hoechst 33258 staining and SEM studies).

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; HeLa Cells; HL-60 Cells; Humans; Nitriles; Oxygen; Triterpenes

Two new triterpenoids, 3-oxotirucalla-7,9(11),24-trien-21-oic acid (1) and 18Hα,3β,20β-ursanediol (2), along with 15 known triterpenes, α-amyrin, α-boswellic acid, β-boswellic acid, acetyl α-boswellic acid, acetyl β-boswellic acid, 9,11-dehydro-β-boswellic acid, 9,11-dehydro-α-boswellic acid, acetyl 11α-methoxy-β-boswellic acid, 11-keto-β-boswellic acid, acetyl 11-keto-β-boswellic acid, acetyl α-elemolic acid, 3β-hydroxytirucalla-8,24-dien-21-oic acid, elemonic acid, 3α-hydroxytirucalla-7,24-dien-21-oic acid, and 3α-hydroxytirucall-24-en-21-oic acid, were isolated from the resin of Boswellia carterii Birdw.

Topics: Boswellia; Drugs, Chinese Herbal; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Resins, Plant; Stereoisomerism; Triterpenes

A rapid and sensitive high-performance thin-layer chromatographic (HPTLC) method was developed and validated for the quantitative estimation of boswellic acids in formulation containing Boswellia serrata extract (BSE) and 11-keto beta-boswellic acid in human plasma. Simple extraction method was used for isolation of boswellic acid from formulation sample and acidified plasma sample. The isolated samples were chromatographed on silica gel 60F(254)-TLC plates, developed using ternary-solvent system (hexane-chloroform-methanol, 5:5:0.5, v/v) and scanned at 260 nm. The linearity range for 11-KBA spiked in 1 ml of plasma was 29.15-145.75 ng with average recovery of 91.66%. The limit of detection and limit of quantification for 11-KBA in human plasma were found to be 8.75 ng/ml and 29.15 ng/ml. The developed method was successfully applied for the assay of market formulations containing BSE and to determine plasma level of 11-keto beta-boswellic acid in a clinical pilot study.

Topics: Boswellia; Chromatography, Thin Layer; Humans; Molecular Structure; Plant Extracts; Reproducibility of Results; Triterpenes

An high-performance TLC (HPTLC) method for the separation of boswellic acids, the active constituents in Boswellia serrata extract, has been developed and TLC of these compounds on silica by automated multiple development (AMD) using solvent gradients was performed. Enhancement of the separation of boswellic acids on HPTLC plates was carried out by AMD chromatography. Densitometric analysis of the developed plate was carried out to quantify the four boswellic acids. 11-Keto-beta-boswellic acid (KBA) and acetyl-11-keto-beta-boswellic acid (AKBA) were quantified by densitometric scanning of the developed plate at 254 nm. beta-Boswellic acid (BA) and acetyl-beta-boswellic acid (ABA) were quantified after derivatization with anisaldehyde sulfuric acid reagent at 560 nm. The AMD system provided a clean separation according to polarity for each of the four groups studied and good results were obtained. The proposed HPTLC method for the simultaneous quantification of the major boswellic acids BA, ABA, KBA, and AKBA was found to be simple, precise, specific, sensitive, and accurate and can be used for routine quality control and for the quantification of these compounds in plant materials. The study of market products revealed significant variations in the content of these pharmacologically active compounds in commercial samples.

Topics: Boswellia; Chromatography, Thin Layer; Plant Extracts; Reference Standards; Silicon Dioxide; Solvents; Terpenes; Triterpenes