Explore the active ingredients and mechanisms in Musa basjoo pseudostem juice against diabetes based on animal experiment, gas chromatography-mass spectrometer and network pharmacology

Background: Musa basjoo pseudostem juice (MBSJ) is a well-known Chinese medicine, and Miao people use MBSJ to treat diabetes. In this work, the active ingredients and molecular mechanism of MBSJ against diabetes were explored. Methods: Anti-diabetic activity of MBSJ was evaluated using diabetic rats, and then the ingredients in the small-polar parts of MBSJ were analyzed by gas chromatography-mass spectrometer (GC-MS). Targets were obtained from several databases to develop the "ingredient-target-disease" network by Cytoscape. A collaborative analysis was carried out using the tools in Cytoscape and R packages, and molecular docking was also performed. Results: MBSJ improved the oral glucose tolerance and insulin tolerance, and reduced fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, and low-density lipoprotein levels in the serum of diabetic rats. 13 potential compounds were identified by GC-MS for subsequent analysis, including Dibutyl phthalate, Oleamide, Stigmasterol, Stigmast-4-en-3-one, etc. The anti-diabetic effect of MBSJ was related to multiple signaling pathways, including Neuroactive ligand-receptor interaction, Phospholipase D signaling pathway, Endocrine resistance, Rap1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking at least partially verified the screening results of network pharmacology. Conclusion: MBSJ had good anti-diabetic activity. The small-polar parts of MBSJ were rich in anti-diabetic active ingredients. Furthermore, the analysis results showed that the anti-diabetic effect of the small-polar parts of MBSJ may be the result of multiple components, multiple targets, and multiple pathways. The current research results can provide important support for studying the active ingredients and exploring the underlying mechanism of MBSJ against diabetes.

Effects of 3FTx Protein Fraction from Naja ashei Venom on the Model and Native Membranes: Recognition and Implications for the Mechanisms of Toxicity

Three-finger toxins are naturally occurring proteins in Elapidae snake venoms. Nowadays, they are gaining popularity because of their therapeutic potential. On the other hand, these proteins may cause undesirable reactions inside the body′s cells. A full assessment of the safety of Naja ashei venom components for human cell application is still unknown. The aim of the study was to determine the effect of the exogenous application of three-finger toxins on the cells of monocytes (U-937) and promyelocytes (HL-60), with particular emphasis on the modification of their membranes under the influence of various doses of 3FTx protein fraction (0–120 ng/mL). The fraction exhibiting the highest proportion of 3FTx proteins after size exclusion chromatography (SEC) separation was used in the experiments. The structural response of cell membranes was described on the basis of single-component and multi-component Langmuir monolayers that mimicked the native membranes. The results show that the mechanism of protein–lipid interactions depends on both the presence of lipid polar parts (especially zwitterionic type of lipids) and the degree of membrane saturation (the greatest-for unsaturated lipids). The biochemical indicators reflecting the tested cells (MDA, LDH, cell survival, induction of inflammation, LD50) proved the results that were obtained for the model.

The Antitumor Mechanism of the Polyphenol-enriched Ethyl Acetate Fraction Extract of Glechoma hederacea (Lamiaceae) against HepG2 Cells Involves Apoptosis Pathways

Background: Glechoma hederacea (Lamiaceae) is a traditional Chinese herb belonging to the Labiatae family and has many biological activities. This study aimed to investigate the in vitro effects of different polar parts of the water extracts of G. hederacea (Lamiaceae) on HepG2 cells and the possible underlying mechanism.Methods: The cytotoxic effects were determined using the MTT assay. Apoptosis was quantified using annexin V-FITC/PI staining. Caspase-3 and caspase-9 activities were measured using PhiphiLux-G1D2 kit. Apoptosis-related protein expression was determined using western blot analysis. Reactive oxygen species (ROS) generation, mitochondrial transmembrane potential (MMP), and calcium ion levels were measured using specific fluorescence probes and flow cytometry. The HepG2 cell antioxidant state was determined using DAPI and comet assay, and antioxidant enzyme activities. The polyphenol contents of different polar parts of fractional extracts were determined using HPLC. Results: Our results showed that rosmarinic acid, caffeic acid, and ferulic acid were the major polyphenolic components in the ethyl acetate fraction extract (EAFE) of G. hederacea L.. EAFE could significantly inhibit HepG2 cell proliferation, induce apoptosis, and cause S phase arrest. The apoptogenic activity of EAFE involved ROS induction, Ca2+ accumulation, glutathione depletion, MMP disruption, caspases 3, 9 activation, and Bax/Bcl-2 ratio increment.Conclusion: Our findings suggest that the polyphenols in the EAFE can inhibit HepG2 cell growth and induce apoptosis through the mitochondria-mediated pathway and ROS-mediated endoplasmic reticulum stress. EAFE could be developed as a functional food or nutraceutical ingredient for chemotherapy.

Solvation heterogeneity in ionic liquids as demonstrated by photo-chemical reactions

It has been recognised that ionic liquids (ILs) with long alkyl-chains have a segregated structure due to the inhomogeneous distribution of polar parts and non-polar parts. This inhomogeneity of ILs brings about unique solvation phenomena of solute molecules dissolved in ILs. We have investigated various solvation-state selective phenomena by using laser spectroscopic techniques such as solvation state selective vibrational spectroscopy, translational and rotational dynamics of small molecules in ILs, and solvation state selective fundamental chemical reactions. In this paper, we have reviewed an intramolecular electron transfer (ET) reaction in the Marcus inverted region of N,N-dimethyl-p-nitroaniline and an intramolecular proton transfer (IPT) reaction in 4′-N,N-diethylamino-3-hydroxyflavone as examples of chemical reactions affected by unique solvation in ILs.

Exploring polar headgroup interactions between sphingomyelin and ceramide with infrared spectroscopy

Ceramide is a major actor in the sphingolipid signaling pathway elicited by various kinds of cell stress. Under those conditions ceramide (Cer) is produced in the plasma membrane as a product of sphingomyelin (SM) hydrolysis, and this may lead to apoptosis. Thus, SM and Cer coexist in the membrane for some time, and they are known to separate laterally from the (more abundant) glycerolipids, giving rise to highly rigid domains or platforms. The properties of these domains/platforms are rather well understood, but the underlying SM:Cer molecular interactions have not been explored in detail. Infrared (IR) spectroscopy is a powerful analytical technique that provides information on all the chemical groupings in a molecule, and that can be applied to membranes and lipid bilayers in aqueous media. IR spectra can be conveniently retrieved as a function of temperature, thus revealing the thermotropic transitions of SM and its mixtures with Cer. Four regions of the IR spectrum of these sphingolipids have been examined, two of them dominated by the hydrophobic regions in the molecules, namely the C–H stretching vibrations (2800–3000 cm−1), and the CH2 scissoring vibrations (1455–1485 cm−1), and two others arising from chemical groups at the lipid-water interface, the sphingolipid amide I band (1600–1680 cm−1), and the phosphate vibrations in the 1000–1110 cm−1 region. The latter two regions have been rarely studied in the past. The IR data from the hydrophobic components show a gel (or ripple)-fluid transition of SM at 40 °C, that is shifted up to about 70 °C when Cer is added to the bilayers, in agreement with previous studies using a variety of techniques. IR information concerning the polar parts is more interesting. The amide I (carbonyl) band of pure SM exhibits a maximum at 1638 cm−1 at room temperature, and its position is shifted by about 10 cm−1 in the presence of Cer. Cer causes also a change in the overall band shape, but no signs of band splitting are seen, suggesting that SM and Cer carbonyl groups are interacting tightly, presumably through H-bonds. The 1086 cm−1 band, corresponding to PO2− vibrations, appears more stable in SM than in DPPC, and it is further stabilized by Cer, again suggesting an important role of H-bonds in the formation of SM:Cer clusters. Thus, SM and Cer can interact through their polar headgroups, in a way that is not accessible to other lipid classes.

Therapeutic Assessment of Fractions of Hawthorn on Gastrointestinal Motility Disorder by UPLC-MS/MS-based Metabolomics

Background: Hawthorn, a commonly-used traditional Chinese medicine (TCM) for treating dyspepsia，dysmenorrhea and hyperlipidemia, etc., has been proven to improve gastrointestinal motility, avoid food retention. Due to its complex ingredients, the active fractions responsible for the treatment of improving digestion remain largely unknown. To explore the underlying material and interpret its potential mechanism, the therapeutic effect of extract from different polar parts of hawthorn on gastrointestinal motility disorder was studied based on the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics . Materials and Methods: The rat model of gastrointestinal motility disorder was established by subcutaneous injecting with atropine. The modeled rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of hawthorn for 5 consecutive days. The stomach, small intestine, plasma samples were collected and then subjected to related measurement (gastric emptying rate and small intestine propulsion rate), UPLC-MS/MS metabolic profiling and multivariate/univariate statistical analysis. Results: The results showed that T3 had the best therapeutic effect, and T1, T2 and T4 with no obvious therapeutic effect, demonstrating that the effective components of hawthorn should be compounds of medium polarity. T3 achieved good therapeutic effects due to the gastrointestinal motility promotion activity, and by rectifying the disturbed amino acid metabolism in gastrointestinal motility disorder model. Conclusion: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of hawthorn on gastrointestinal motility disorder, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

The Protective Effect of Different Polar Solvent Extracts of Er Miao San on Rats with Adjuvant Arthritis

Objective. The aim of this study was to evaluate the antiarthritic effects of different polar solvent extracts of Er Miao San (EMS) on model rats with adjuvant arthritis (AA) and screen the effective pats of EMS in the treatment of arthritis. Methods. Four different polar solvent extracts of EMS such as petroleum ether (PE), methylene chloride (CH2Cl2), ethyl acetate (EtOAc), and n-butanol (n-BuOH) were extracted and separated by different solvent polar extraction. Different polar parts of the aqueous extract of EMS were orally administered for 14 days to AA rats. Progression of clinical signs such as edema of paws and polyarthritis index was measured. The ankle joint changes were observed by pathological sections. ELISA was used to measure cytokines in the serum according to the manufacturer’s instructions. UHPLC measured the effective parts of EMS. Results. Administration of EtOAc and CH2Cl2 parts remarkably inhibited the paw swelling, decreased the index of arthritis, decreased the body weight loss, and improved the changes of histopathology. Furthermore, the concentrations of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) were significantly lower, while the anti-inflammatory cytokine (IL-10) was remarkably higher compared with that in the model group. And the result of UHPLC analysis indicated that the effective parts of EMS contain berberine and atractylodin. Conclusions. EtOAc and CH2Cl2 are the effective parts of EMS that can improve arthritis. In particular, berberine and atractylodin may be responsible for the antiarthritic activity of EMS. This research provided pharmacological and chemical foundation for the application of EMS in treating rheumatoid arthritis (RA).

Heun Polynomials and Exact Solutions for the Massless Dirac Particle in the C-Metric

The equation of motion of a massless Dirac particle in the C-metric leads to the general Heun equation (GHE) for the radial and the polar variables. The GHE, under certain parametric conditions, is cast in terms of a new set of su(1, 1) generators involving differential operators of degrees ±1/2 and 0. Additional Heun polynomials are obtained using this new algebraic structure and are used to construct some exact solutions for the radial and the polar parts of the Dirac equation.