The Activity of Prebiotics and Probiotics in Hepatogastrointestinal Disorders and Diseases Associated with Metabolic Syndrome.

The components of metabolic syndrome (MetS) and hepatogastrointestinal diseases are widespread worldwide, since many factors associated with lifestyle and diet influence their development and correlation. Due to these growing health problems, it is necessary to search for effective alternatives for prevention or adjuvants in treating them. The positive impact of regulated microbiota on health is known; however, states of dysbiosis are closely related to the development of the conditions mentioned above. Therefore, the role of prebiotics, probiotics, or symbiotic complexes has been extensively evaluated; the results are favorable, showing that they play a crucial role in the regulation of the immune system, the metabolism of carbohydrates and lipids, and the biotransformation of bile acids, as well as the modulation of their central receptors FXR and TGR-5, which also have essential immunomodulatory and metabolic activities. It has also been observed that they can benefit the host by displacing pathogenic species, improving the dysbiosis state in MetS. Current studies have reported that paraprobiotics (dead or inactive probiotics) or postbiotics (metabolites generated by active probiotics) also benefit hepatogastrointestinal health.

Aberrant sphingomyelin 31P-NMR signatures in giant cell tumour of bone.

An understanding of the biochemistry of the giant cell tumour of bone (GCTB) provides an opportunity for the development of prognostic markers and identification of therapeutic targets. Based on metabolomic analysis, we proposed glycerophospholipid metabolism as the altered pathway in GCTB., The objective of this study was to identify these altered metabolites. Using phosphorus-31 nuclear magnetic resonance spectroscopy (31P-NMR), sphingomyelin was determined to be the most dysregulated phospholipid in tissue samples from six patients with GCTB. Enzymes related to its biosynthesis and hydrolysis were examined using immunodetection techniques. High expression of sphingomyelin synthases 1 and 2, but low expression of neutral sphingomyelinase 2 (nSMase2) was found in GCTB tissues compared to non-neoplastic bone tissues. Sphingomyelin/ceramide biosynthesis is dysregulated in GCTB due to alterations in the expression of SMS1, SMS2, and nSMase2.

Metabolic profiling of serum in patients with cartilage tumours using 1 H-NMR spectroscopy: A pilot study.

Cartilage-forming lesions include tumours that can vary in severity from benign enchondromas to high-grade malignant chondrosarcomas. Chondrosarcoma is the second most frequent malignant bone tumour, accounting for 20-30% of all malignant bone neoplasms. Surgery is the standard treatment for cartilage tumours (CTs); however, their incidental diagnosis and the difficult differentiation of low-grade lesions like chondrosarcoma grade I from benign entities like enchondroma are challenges for clinical management. In this sense, the search for circulating biomarkers for early detection and prognosis is an ongoing interest. Targeted metabolomics is a powerful tool that can propose potential biomarkers in biological fluids as well as help to discover disturbed metabolic pathways to reveal tumour pathogenesis. In this context, the aim of this study was to investigate the 1 H nuclear magnetic resonance metabolomic serum profile of patients with CTs contrasted with healthy controls. Forty-one metabolites were identified and quantified; the multivariate statistical methods principal component analysis and partial least squares discriminant analysis reveal a clear separation of the CT group, that is, the differential metabolites that were involved in two main metabolic pathways: the taurine and hypotaurine metabolism and synthesis and degradation of ketone bodies. Our results represent preliminary work for emergent serum-based diagnostics or prognostic methods for patients with chondrogenic tumours.

1 H-NMR Based Metabolomics Profiling of Citrus Juices Produced in Veracruz, México.

This study describes the 1 H-NMR-based metabolomics profiling of juices from citrus fruits harvested in the state of Veracruz, México. The hydrophilic profile of commercial lemons (Agrio and Persian), tangerines (Fremont and Mónica), oranges (Valencia and Washington Navel), and grapefruits (Red Ruby and Rio Red) was determined. According to our results, 35 metabolites were identified in the 1 H-NMR profiling. The statistical differences obtained by PCA and OPLS-DA revealed that specific amino acids, sugars, and organic acids were differential metabolites in the species and cultivars studied. High endogenous levels of sucrose (10-190 mM), α-glucose, ß-glucose (α- and ß-isomers, 40-205 mm), and fructose (36-170 mm) were detected in the juices of grapefruits, oranges, and tangerines, whereas citric acid (40-530 mm) was the principal organic acid in the juices of lemons. To calculate the specific amounts of metabolites from these species and their cultivars, the results were finely analyzed using the qNMR method. According to these calculations, Valencia oranges had the highest concentration of ascorbic acid (>2 mm). The described 1 H-NMR method is highly reproducible, inexpensive, and highly robust in comparison to other analytical methods used to determine the hydrophilic profile of citrus juices.

Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver.

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

Absolute configuration of the diterpenoids icetexone and conacytone from Salvia ballotaeflora.

Detailed literature inspections regarding the diterpenoids icetexone (1) and conacytone (3) reveal that the absolute configuration (AC) of these natural occurring compounds is not rigorously proven, despite they were originally isolated in 1976. This task is now completed by single-crystal X-ray diffraction Flack and Hooft parameters determination after processing data collected with Cu Kα graphite monochromated radiation. The AC of both compounds is further determined by vibrational circular dichroism measurements performed on icetexone acetate (2) and conacytone triacetate (4) since the solubility of 1 and 3 is limited. Comparison of the substituent chemical shifts (SCS) induced by acetylation of 1 and 3 to afford 2 and 4, respectively, reveals that in the case of icetexone, all six SCS values of the quinone ring are in excellent agreement with the expected values, while in the case of conacytone, three agree and three do not agree due to the presence of additional acetates near the quinone ring. Density functional theory calculations performed on 3-hydroxythymoquinone (6) and its tautomer 4-hydroxy-1,2-quinone 7, on 6-hydroxythymoquinone (8) and its tautomer ortho-quinone 9, and on icetexone (1) and the claimed natural occurring ortho-quinone tautomer romulogarzone (5) indicate that 2-hydroxy-1,4-quinones are more stable, by some 11-14 kcal/mol, than their 4-hydroxy-1,2-quinone tautomers, and therefore, romulogarzone (5) is inexistent.

Absolute configuration of the ocimene monoterpenoids from Artemisia absinthium.

The absolute configuration (AC) of the naturally occurring ocimenes (-)-(3S,5Z)-2,6-dimethyl-2,3-epoxyocta-5,7-diene (1) and (-)-(3S,5Z)-2,6-dimethylocta-5,7-dien-2,3-diol (2), isolated from the essential oils of domesticated specimens of Artemisia absinthium, followed by vibrational circular dichroism (VCD) studies of 1, as well as from the acetonide 3 and the monoacetate 4, both derived from 2, since secondary alcohols are not the best functional groups to be present during VCD studies in solution due to intermolecular associations. The AC follows from comparison of experimental and calculated VCD spectra that were obtained by Density Functional Theory computation at the B3LYP/DGDZVP level of theory. Careful nuclear magnetic resonance (NMR) measurements were compared with literature values, providing for the first time systematic 1 H and 13 C chemical shift data. Regarding homonuclear 1 H coupling constants, after performing a few irradiation experiments that showed the presence of several small long-range interactions, the complete set of coupling constants for 3, which is representative of the four studied molecules, was determined by iterations using the PERCH software. This procedure even allowed assigning the pro-R and pro-S methyl group signals of the two gem-dimethyl groups present in 3.

Complete 1 H NMR assignment of cedranolides.

Complete and unambiguous 1 H NMR chemical shift assignment of α-cedrene (2) and cedrol (9), as well as for α-pipitzol (1), isocedrol (10), and the six related compounds 3-8 has been established by iterative full spin analysis using the PERCH NMR software (PERCH Solutions Ltd., Kuopio, Finland). The total sets of coupling constants are described and correlated with the conformational equilibria of the five-membered ring of 1-10, which were calculated using the complete basis set method. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of antioxidant and hepatoprotective effects of white cabbage essential oil.

CONTEXT: There have been no reports of the extraction of essential oil (EO) from white cabbage [Brassica oleracea L. var. capitata (L.) Alef. f. alba DC. (Brassicaceae)] (Bocfal) or its chemical composition, antioxidant activity, or hepatoprotective effects. OBJECTIVE: To extract Bocfal EO, to identify and quantify its chemical components, to assess their antioxidant capacity, and to evaluate the hepatoprotective properties of Bocfal EO. MATERIALS AND METHODS: Bocfal EO was obtained using hydrodistillation (200 mm Hg/58 °C). The chemical composition was analyzed using GC-MS and was quantified using GC-FID. The antioxidant activity of Bocfal EO and its main constituents was evaluated using TBARS in rat brain homogenates. A Bocfal EO hepatoprotective effect (192 mg/kg) on acute carbon tetrachloride (CT)-induced liver damage was determined in rats using biochemical markers and histological analysis. Diallyl disulphide (DADS) (1 mmol/kg) was used as a control for comparison. RESULTS: Bocfal EO contained organic polysulphides (OPSs), such as dimethyl trisulphide (DMTS) 65.43 ± 4.92% and dimethyl disulphide (DMDS) 19.29 ± 2.16% as major constituents. Bocfal EO and DMTS were found to be potent TBARS inhibitors with IC50 values of 0.51 and 3 mg/L, respectively. Bocfal EO demonstrated better hepatoprotective properties than did DADS (p < 0.05), although both slightly affected the hepatic parenchyma per se, as observed using histopathology. DISCUSSION AND CONCLUSION: The antioxidant properties of Bocfal EO and DMTS may be the mechanism of hepatoprotective action; the parenchymal disturbances by Bocfal EO or DADS alone may be related to the high doses used.

Relative Stereochemistry and Absolute Configuration of Farinosin, a Eudesmanolide From Encelia farinosa.

The naturally occurring eudesmanolide farinosin () is now fully characterized for the first time despite its original isolation almost half a century ago. The early assumed relative stereochemistry and absolute configuration were confirmed by vibrational circular dichroism together with evaluation of the Hooft X-ray parameters. The molecular conformation is very similar in the gas stage and in the solid state. Chirality 28:415-419, 2016. © 2016 Wiley Periodicals, Inc.

Structure and antimicrobial activity of phloroglucinol derivatives from Achyrocline satureioides.

The new prenylated phloroglucinol α-pyrones 1-3 and the new dibenzofuran 4, together with the known 23-methyl-6-O-demethylauricepyrone (5), achyrofuran (6), and 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphaliin A), were isolated from the aerial parts of Achyrocline satureioides. Their structures were determined by 1D and 2D NMR spectroscopic studies, while the absolute configuration of the sole stereogenic center of 1 was established by vibrational circular dichroism measurements in comparison to density functional theory calculated data. The same (S) absolute configuration of the α-methylbutyryl chain attached to the phloroglucinol nucleus was assumed for compounds 2-6 based on biogenetic considerations. Derivatives 7-16 were prepared from 1 and 5, and the antimicrobial activities of the isolated metabolites and some of the semisynthetic derivatives against a selected panel of Gram-positive and Gram-negative bacteria, as well as a set of yeast molds, were determined.

Complete 1H NMR assignments of pyrrolizidine alkaloids and a new eudesmanoid from Senecio polypodioides.

Chemical investigation of the aerial parts of Senecio polypodioides lead to the isolation of the new eudesmanoid 1ß-angeloyloxyeudesm-7-ene-4ß,9α-diol (1) and the known dirhamnosyl flavonoid lespidin (3), while from roots, the known 7ß-angeloyloxy-1-methylene-8α-pyrrolizidine (5) and sarracine N-oxide (6), as well as the new neosarracine N-oxide (8), were obtained. The structure of 1 and 8 was elucidated by spectral means. Complete assignments of the (1)H NMR data for 5, 6, sarracine (7), and 8 were made using one-dimensional and two-dimensional NMR experiments and by application of the iterative full spin analysis of the PERCH NMR software.

Stereospecific (5) JHortho,OMe couplings in methoxyindoles, methoxycoumarins, and methoxyflavones.

Long-range coupling constants (5) JHortho,OMe were measured in series of methoxyindoles, methoxycoumarins, and methoxyflavones by the modified J doubling in the frequency domain method. The COSY and NOESY spectra revealed the coupling of the -OMe group with a specific proton at the ortho position and its preferred conformation. Homonuclear (1) H-(1) H couplings were confirmed by irradiation of the -OMe signal. Density functional theory calculations of (5) JHortho,OMe using the modified aug-cc-pVTZ basis set evidenced that the Fermi contact term shows good agreement with the experimental J values. Accurate chemical shift and coupling constant values followed after iterative quantum mechanical spectral analysis using the PERCH software.

The ketone body ß-Hydroxybutyrate as a fuel source of chondrosarcoma cells.

Chondrosarcoma (CS) is a malignant bone tumor arising from cartilage-producing cells. The conventional subtype of CS typically develops within a dense cartilaginous matrix, creating an environment deficient in oxygen and nutrients, necessitating metabolic adaptation to ensure proliferation under stress conditions. Although ketone bodies (KBs) are oxidized by extrahepatic tissue cells such as the heart and brain, specific cancer cells, including CS cells, can undergo ketolysis. In this study, we found that KBs catabolism is activated in CS cells under nutrition-deprivation conditions. Interestingly, cytosolic ß-hydroxybutyrate dehydrogenase 2 (BDH2), rather than mitochondrial BDH1, is expressed in these cells, indicating a specific metabolic adaptation for ketolysis in this bone tumor. The addition of the KB, ß-Hydroxybutyrate (ß-HB) in serum-starved CS cells re-induced the expression of BDH2, along with the key ketolytic enzyme 3-oxoacid CoA-transferase 1 (OXCT1) and monocarboxylate transporter-1 (MCT1). Additionally, internal ß-HB production was quantified in supplied and starved cells, suggesting that CS cells are also capable of ketogenesis alongside ketolysis. These findings unveil a novel metabolic adaptation wherein nutrition-deprived CS cells utilize KBs for energy supply and proliferation.

Diorganotin (IV) amino acid complexes as potential anticancer agents. Synthesis, structural characterization, and in vitro assays.

Nine new organotin (IV) derivatives from L-amino acids (l-lysine, L-ornithine, L-glutamic acid, and L-aspartic acid) were synthesized by one-pot ultrasound-assisted methodology. All compounds were characterized by ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared), LRMS (Low-Resolution Mass Spectrometry), and solution NMR (1H, 13C, 119Sn Nuclear Magnetic Resonance) spectroscopies. Complexes Bu2Sn(Lys) (1), Ph2Sn(Lys) (2), Bu2Sn(Orn) (3), and Ph2Sn (Glu-OMe) (6a) were crystallized, and the structures were established by single-crystal X-ray diffraction analysis. Diffraction results evidenced that complexes 1 to 3 were five-coordinated mononuclear species while the phenyl substituted derivative Ph2Sn (Glu-OMe) (6a) forms a polymeric network via Sn-O-Sn bridging whereby the tin atom is six-coordinated. In turn, 119Sn NMR results revealed that all tin complexes exist as mononuclear penta-coordinated species in solution. The tin derivatives were screened for ADME (Adsorption, Distribution, Metabolism, and Excretion) properties via the freely available tools SWISS ADME, and the results were analyzed hereafter. The antiproliferative activity of the complexes was tested against three human cancer cell lines: colorectal adenocarcinoma HT-29, breast adenocarcinoma MDA-MB-231, and chondrosarcoma SW-1353 using a non-tumoral cell line of human osteoblast as control, demonstrating selective inhibitory activities against cancer cells. Hence, these compounds could be a promising alternative to classical chemotherapy agents.

NMR-based conformational analysis of perezone and analogues.

Complete assignment of the (1)H NMR chemical shift and coupling constant values of perezone (1), O-methylperezone (2) and 6-hydroxyperezone (3) was carried out by total-line-shape-fitting calculations using the PERCH iterative spectra analysis software (PERCH Solutions Ltd., Kuopio, Finland). The resulting simulated spectra for the three compounds showed strong similarity to their corresponding experimental spectra. Particularly, all vicinal, allylic and homoallylic coupling constant values for the side chain of the three compounds were very similar, thus revealing that the conformation of these three molecules in solution is indeed almost identical. This fact is in agreement with extended side chain conformations over folded chain conformations because 1, 2 and 3 undergo completely different intramolecular cycloaddition reactions. In addition, results of double pulsed field gradient spin echo NOESY 1D experiments performed on perezone (1) were unable to provide evidence for folded conformers.

Deuterium-induced isotope effects on the 13C chemical shifts of α-D-glucose pentaacetate.

1,2,3,4,6-Penta-O-acetyl-α-D-glucopyranose and the corresponding [1-(2)H], [2-(2)H], [3-(2)H], [4-(2)H], [5-(2)H], and [6,6-(2)H(2)]-labeled compounds were prepared for measuring deuterium/hydrogen-induced effects on (13)C chemical shift (n)Δ (DHIECS) values. A conformational analysis of the nondeuterated compound was achieved using density functional theory (DFT) molecular models that allowed calculation of several structural properties as well as Boltzmann-averaged (13)C NMR chemical shifts by using the gauge-including atomic orbital method. It was found that the DFT-calculated C-H bond lengths correlate with (1)Δ DHIECS.

Prebiotics and Probiotics: Effects on Dyslipidemia and NAFLD/NASH and the Associated Mechanisms of Action.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is now considered the most common chronic liver disease worldwide. NAFLD is related to changes in lipid metabolism and is characterized by the increase or accumulation of fat in hepatocytes that may progress to nonalcoholic steatohepatitis (NASH), which leads to the appearance of inflammatory processes. Treatment consists of changes in diet, physical activity, and weight control; however, these disorders represent a health problem and require the development of novel alternatives to treatment and prevention. NAFLD/NASH are strongly associated with other disorders, such as metabolic syndrome (MetS); in fact, NAFLD is considered the hepatic manifestation of MetS. These disorders are related to other components of MetS, including dyslipidemia, which is characterized by an imbalance in blood cholesterol and triglyceride levels. Prebiotics and probiotics benefit from treating and preventing several ailments, including liver diseases. Specifically, in dyslipidemia, NAFLD, and NASH, probiotics play a fundamental role in conducting the biotransformation of primary bile acids into secondary bile acids, which generally have important activity as immunomodulators and metabolism regulators. The mechanisms of action of pre and probiotics involve the activity of bile acid receptors, such as FXR and TGR-5, and the events resulting from their activation. Therefore, prebiotics and probiotics may be reasonable options to prevent and treat metabolic- related liver diseases.

Absolute configuration and 1H NMR characterization of rosmaridiphenol diacetate.

The correction of patented structure 1 of rosmaridiphenol, an antioxidant isolated from rosemary, Rosmarinus officinalis, was made recently. The correct structure is proposed as 11,12-dihydroxy-8,11,13-icetexatrien-1-one (2a) based on 2D NMR data. In order to further support the structure, this work reports the single-crystal X-ray analysis, the complete (1)H NMR assignment by full spin-spin simulation, and the absolute configuration of the diacetate 2b derived via vibrational circular dicroism measurements in comparison with density functional theory calculated data.

A Key Metabolic Regulator of Bone and Cartilage Health.

Taurine, a cysteine-derived zwitterionic sulfonic acid, is a common ingredient in energy drinks and is naturally found in fish and other seafood. In humans, taurine is produced mainly in the liver, and it can also be obtained from food. In target tissues, such as the retina, heart, and skeletal muscle, it functions as an essential antioxidant, osmolyte, and antiapoptotic agent. Taurine is also involved in energy metabolism and calcium homeostasis. Taurine plays a considerable role in bone growth and development, and high-profile reports have demonstrated the importance of its metabolism for bone health. However, these reports have not been collated for more than 10 years. Therefore, this review focuses on taurine-bone interactions and covers recently discovered aspects of taurine's effects on osteoblastogenesis, osteoclastogenesis, bone structure, and bone pathologies (e.g., osteoporosis and fracture healing), with due attention to the taurine-cartilage relationship.