Lipophilic Compounds and Antibacterial Activity of Opuntia ficus-indica Root Extracts from Algeria.

The chemical composition, investigated by gas chromatography-mass spectrometry, and antibacterial activity of lipophilic extractives of three varieties of Opuntia ficus-indica roots from Algeria are reported in this paper for the first time. The results obtained revealed a total of 55 compounds, including fatty acids, sterols, monoglycerides and long chain aliphatic alcohols that were identified and quantified. ß-Sitosterol was found as the major compound of the roots of the three varieties. Furthermore, considerable amounts of essential fatty acids (ω3, ω6, and ω9) such as oleic, linoleic, and linolenic acids were also identified. The green variety was the richest among the three studied varieties. The antibacterial activity, evaluated with disc diffusion method, revealed that lipophilic extracts were effective mainly against Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) (19~23 mm). Gram-negative strains mainly Pseudomonas aeruginosa gave an inhibition zone of 18 mm, which is considered high antibacterial activity. The minimal inhibitory concentrations of the tested bacteria revealed interesting values against the majority of bacteria tested: 75-100 µg mL-1 for Bacillus sp., 250-350 µg/mL for the two Staphylococcus strains, 550-600 µg mL-1 for E. coli, and 750-950 µg mL-1 obtained with Pseudomonas sp. This study allows us to conclude that the lipophilic fractions of cactus roots possess interesting phytochemicals such as steroids, some fatty acids and long chain alcohols that acted as antibiotic-like compounds countering pathogenic strains.

Anti-Inflammatory, Antioxidant, Chemical Characterization, and Safety Assessment of Argania spinosa Fruit Shell Extract from South-Western Morocco.

Argania spinosa (L.) plays an important role in the Moroccan agroeconomy, providing both employment and export revenue. Argan oil production generates different by-products with functionalities that are not yet investigated, in particular, the shell fruit. The present study aims, for the first time, at evaluating the acute and subacute toxicity, anti-inflammatory, and antioxidant effects of argan fruit shell ethanol extract (AFSEE). The LD50 of AFSEE was determined to be greater than the 5000 mg/kg body weight of mice. No significant variation in the body and organ weights was observed after 28 days of AFSEE treatment compared to that of the control group. Biochemical parameters and histopathological examination revealed no toxic effects of AFSEE. The AFSEE produced a significant inhibition of xylene-induced ear edema in mice. AFSEE reduced significantly the paw edema in mice after carrageenan injection. The chemical characterization showed that AFSEE contains a high level of total phenol content, flavonoids, condensed tannins, and flavanols. The obtained IC50 of DPPH, ABTS, reducing power, and ß-carotene demonstrates that AFSEE has a potential antioxidant effect. The results indicate that AFSEE was safe and nontoxic to mice even at higher doses. Furthermore, the present findings demonstrate that AFSEE has potential anti-inflammatory and antioxidant activities.

Ginkwanghols A and B, osteogenic coumaric acid-aliphatic alcohol hybrids from the leaves of Ginkgo biloba.

Ginkgo biloba (Ginkgoaceae), commonly known as "ginkgo", is called a living fossil, and it has been cultivated early in human history for various uses in traditional medicine and as a source of food. As part of ongoing research to explore the chemical diversity and biologically active compounds from natural resources, two new coumaric acid-aliphatic alcohol hybrids, ginkwanghols A (1) and B (2) were isolated from the leaves of G. biloba. The coumaric acid-aliphatic alcohol hybrids of natural products have rarely been reported. The structures of the new compounds were determined by extensive NMR spectroscopic analysis, HRESI-MS, and quantum chemical ECD calculations, and by comparing the experimental HRESI-MS/MS spectrum of chemically transformed compound 1a with the predicted HRESI-MS/MS spectra proposed from CFM-ID 3.0, a software tool for MS/MS spectral prediction and MS-based compound identification. Ginkwanghols A (1) and B (2) increased alkaline phosphatase (ALP) production in C3H10T1/2, a mouse mesenchymal stem cell line, in a dose-dependent manner. In addition, ginkwanghols A and B mediated the promotion of osteogenic differentiation as indicated by the induction of the mRNA expression of the osteogenic markers ALP and osteopontin (OPN).

Phospholipase D inhibitors screening: Probing and evaluation of ancient and novel molecules.

Phospholipase D (PLD) is a ubiquitous enzyme that cleaves the distal phosphoester bond of phospholipids generating phosphatidic acid (PA). In plants, PA is involved in numerous cell responses triggered by stress. Similarly, in mammals, PA is also a second messenger involved in tumorigenesis. PLD is nowadays considered as a therapeutic target and blocking its activity with specific inhibitors constitutes a promising strategy to treat cancers. Starting from already described PLD inhibitors, this study aims to investigate the effect of their structural modifications on the enzyme's activity, as well as identifying new potent inhibitors of eukaryotic PLDs. Being able to purify the plant PLD from Vigna unguiculata (VuPLD), we obtained a SAXS model of its structure. We then used a fluorescence-based test suitable for high-throughput screening to review the effect of eukaryotic PLD inhibitors described in the literature. In this regard, we found that only few molecules were in fact able to inhibit VuPLD and we confirmed that vanadate is the most potent of all with an IC50 around 58 µM. Moreover, the small-scale screening of a chemical library of 3120 compounds allowed us to optimize the different screening's steps and paved the way towards the discovery of new potent inhibitors.

Machine learning decodes chemical features to identify novel agonists of a moth odorant receptor.

Odorant receptors expressed at the peripheral olfactory organs are key proteins for animal volatile sensing. Although they determine the odor space of a given species, their functional characterization is a long process and remains limited. To date, machine learning virtual screening has been used to predict new ligands for such receptors in both mammals and insects, using chemical features of known ligands. In insects, such approach is yet limited to Diptera, whereas insect odorant receptors are known to be highly divergent between orders. Here, we extend this strategy to a Lepidoptera receptor, SlitOR25, involved in the recognition of attractive odorants in the crop pest Spodoptera littoralis larvae. Virtual screening of 3 million molecules predicted 32 purchasable ones whose function has been systematically tested on SlitOR25, revealing 11 novel agonists with a success rate of 28%. Our results show that Support Vector Machine optimizes the discovery of novel agonists and expands the chemical space of a Lepidoptera OR. More, it opens up structure-function relationship analyses through a comparison of the agonist chemical structures. This proof-of-concept in a crop pest could ultimately enable the identification of OR agonists or antagonists, capable of modifying olfactory behaviors in a context of biocontrol.

Silychristin derivatives conjugated with coniferylalcohols from silymarin and their pancreatic α-amylase inhibitory activity.

Silymarin is a mixture of flavonolignans extracted from the fruit of Silybum marianum (milk thistle). The latter is used as a medicinal plant to treat liver and gallbladder disorders. Recently, silymarin has been investigated for its effects against diabetes mellitus, and shown to reduce serum levels of glucose in model animals and in clinical trials. This effect can be explained mainly by the protective effect of silymarin against pancreatic beta-cells, but the involvement of other mechanisms is possible. We demonstrated the α-amylase inhibitory activity of silymarin and investigated the components responsible for this effect. Two major flavonolignans, silibinin and silychristin, did not show inhibition against α-amylase, but two novel silychristin derivatives conjugated with dehydrodiconiferyl alcohol were isolated as the mildly inhibiting components of silymarin. Further analyses indicated the presence of various silychristin derivatives in silymarin that may act synergistically to show α-amylase inhibitory activity.[Formula: see text].

Hydroalcoholic extract from Origanum vulgare induces a combined anti-mycobacterial and anti-inflammatory response in innate immune cells.

In nature, many plants or their extracted compounds have been found to possess anti-inflammatory features and therapeutic properties against infectious as well as non-infectious diseases, including cancer. In this study, we analysed the immunomodulatory effects on innate immune cells of hydroalcoholic extract from Origanum vulgare L. ssp. hirtum (HyE-Ov), a plant traditionally known for its anti-oxidative properties. The effects of HyE-Ov were tested on human monocyte derived dendritic cells (DC), type-1 (M1) and type-2 macrophages (M2) infected with M. bovis Bacille Calmette-Guérin (BCG), used as a model of persistent intracellular bacterium. DC, M1 and M2 treated with HyE-Ov significantly enhanced their mycobactericidal activity, which was associated with phagosomal acidification in M1 and M2 and increase of phagosomal, but not mitochondrial ROS production in M1, M2, and DC. Treatment of BCG-infected DC with HyE-Ov significantly reduced TNF-α and IL-12 production and increased TGF-ß synthesis. Finally, experiments were repeated using eight different HPLC fractions of HyE-Ov. Results showed that the capability to activate anti-microbial and anti-inflammatory response is shared by different fractions, suggesting that diverse bioactive molecules are present within the hydroalcoholic extract. Altogether, these results show that HyE-Ov promotes anti-mycobacterial innate immunity and limits inflammatory response in vitro and suggest that this plant extract may be exploitable as phytocomplex or nutraceutical for novel host-directed therapeutic approaches.

Discovery of alkoxy benzamide derivatives as novel BPTF bromodomain inhibitors via structure-based virtual screening.

Bromodomain PHD finger transcription factor (BPTF), a bromodomain-containing protein, plays a crucial role in the regulation of downstream gene expression through the specific recognition of lysine acetylation on bulk histones. The dysfunction of BPTF is closely involved with the development and progression of many human diseases, especially cancer. Therefore, BPTF bromodomain has become a promising drug target for epigenetic cancer therapy. However, unlike BET family inhibitors, few BPTF bromodomain inhibitors have been reported. In this study, by integrating docking-based virtual screening with biochemical analysis, we identified a novel selective BPTF bromodomain inhibitor DCB29 with the IC50 value of 13.2 ±â€¯1.6 µM by homogenous time-resolved fluorescence resonance energy transfer (HTRF) assays. The binding between DCB29 and BPTF was confirmed by NMR and SPR. Molecular docking disclosed that DCB29 occupied the pocket of acetylated H4 peptide substrate and provided detailed SAR explanations for its derivatives. Collectively, DCB29 presented great potential as a powerful tool for BPTF-related biological research and further medicinal chemistry optimization.

Types of antiseptics, presentations and rules of use. / Tipos de antisépticos, presentaciones y normas de uso.

Antiseptics are chemical substances that when applied topically onto intact skin, mucous membranes or wounds partially or completely reduces the population of living microorganisms in those tissues. Different types of antiseptics are available - those most commonly used in clinical practice being alcohols, iodinated compounds and chlorhexidine. When using an antiseptic, consideration is required of its spectrum of antimicrobial activity, latency, residual effects, possible interferences of the presence of organic material with the activity of the antiseptic, its side effects, compatibility with other antiseptics, and cost. This article is part of a supplement entitled "Antisepsis in the critical patient", which is sponsored by Becton Dickinson.

Effect of Skin Maceration Treatment on Aroma Profiles of Kiwi Wines Elaborated with Actinidia deliciosa "Xuxiang" and A. chinensis "Hort16A".

Background: Kiwi has become an important and promising fruit to ferment kiwi wine in recent years in China. Objective: The objective of this study was to evaluate the effect of skin maceration treatment on aroma profiles of kiwi wine elaborated with two representative kiwi varieties (Actinidia deliciosa "Xuxiang" and A. chinensis "Hort16A"). Methods: Aroma profiles were characterized using solid-phase microextraction GC-MS method. Principal component analysis was used to separate and group the wines as well as for identifying the aroma components that best differentiate the wines. Results: Esters and alcohols were the two most abundant compounds in kiwi wine. Skin maceration treatment gave rise to a positive effect of aroma profiles, resulting in a significant increase of terpenes. A total of 11 volatile compounds were found at concentrations higher than their odor threshold in kiwi wine samples. Conclusions: The study could play a role in laying a foundation for the development of the kiwi fruit wine industry. Highlights: Different aroma profiles were presented because of variety differences. Skin maceration treatment gave rise to a positive effect of aroma profiles, which resulted in a significant increase of terpenes.

Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling.

Clinically, low and moderate alcohol intake improves human health with protection against metabolic syndromes, including type 2 diabetes; however, mechanisms that are associated with these effects remain to be elucidated. The aims of this study were to investigate the effects of moderate alcohol intake on thermogenic brown/beige adipocyte formation and glucose and lipid homeostasis, as well as the involvement of retinoic acid (RA) signaling in the entire process. C57BL6 male mice were supplemented with 8% (w/v) alcohol in water for 1 or 4 mo. Alcohol intake prevented body weight gain, induced the formation of uncoupling protein 1-positive beige adipocytes in white adipose tissue, and increased thermogenesis in mice, which is associated with decreased serum glucose and triacylglycerol levels. Mechanistically, alcohol intake increased RA levels in serum and adipose tissue, which was associated with increased expression of aldehyde dehydrogenase family 1 subfamily A1 (Aldh1a1). When RA receptor-α signaling was conditionally blocked in platelet-derived growth factor receptor-α-positive adipose progenitors, the effects of alcohol on beige adipogenesis were largely abolished. Finally, moderate alcohol prevented high-fat diet-induced obesity and metabolic dysfunction. In conclusion, moderate alcohol intake induces thermogenic brown/beige adipocyte formation and promotes glucose and lipid oxidation via elevation of RA signaling.-Wang, B., Wang, Z., de Avila, J. M., Zhu, M.-J., Zhang, F., Gomez, N. A., Zhao, L., Tian, Q., Zhao, J., Maricelli, J., Zhang, H., Rodgers, B. D., Du, M. Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling.

Antimicrobial Metabolites from a Marine-Derived Actinomycete in Vietnam's East Sea.

Two new compounds, a quinoline alkaloid (1) and a 1,4-dioxane derivative (2), were isolated from culture broth of the marine-derived actinomycete Micromonospora sp. (strain G019) by bioassay-guided fractionation. This actinomycete strain was isolated from sediment, collected at Cát Bà Peninsula, Vietnam. The taxonomic identification was achieved by analysis of 16S rRNA gene sequences. On the basis of morphological and phylogenetic evidence, strain G019 was assigned to the genus Micromonospora. The structures of 1 and 2 were established by spectroscopic data analysis, including one- and two-dimensional NMR, and MS. Compound 1 was found to have antibacterial activity against Escherichia coli (MIC: 48 µg/mL), Salmonella enterica (MIC: 96 µg/mL) and Enterococcus faecalis (MIC: 128 µg/mL), while compound 2 showed inhibitory activity against Enterococcusfaecalis (MIC: 32 µg/mL) and Candida albicans (MIC: 64 µg/mL).

Immunostimulating activity of polyhydric alcohol isolated from Taxus cuspidata.

A polyhydric alcohol (PAL) was isolated from Taxus cuspidata and its immunostimulatory activities were assessed. The primary monosaccharide composition of the PAL was determined to be glucose, where HPAEC analysis showed no significant amount of any other sugars. However, glycerol and xylitol were identified as the main sugar alcohols. Fourier-transform infrared (FT-IR) analysis indicated that the purified PAL is a complex glycitol, which structurally contains significant amount of hydroxyl groups. MALDI-TOF mass spectroscopy also demonstrated that PAL is a complex glycitol built in hexose polymerization. Enzyme linked immunosorbent assay showed that the PAL stimulates the release of the proinflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. Furthermore, treatment of RAW 264.7 cells with PAL for 24h remarkably increased the phosphorylation levels of ERK, p38 and JNK in a dose-dependent manner, whereas the total protein levels of ERK (t-ERK), p38 (t-p38) and JNK (t-JNK) remained unchanged. These results clearly demonstrate that PAL stimulates the immune response in RAW 264.7 cells through the activation of MAPKs (ERK, p38 and JNK) signaling pathway. To the best of our knowledge, this is the first study to demonstrate the primary structure and immune-stimulating activities of PAL from the fruit of T. cuspidata.

What caused the changes in the usage of Atractylodis Macrocephalae Rhizoma from ancient to current times?

Ancient Chinese medicine treatises on Atractylodis Macrocephalae Rhizoma (AMR), the rhizome of Atractylodes macrocephala Koidz, indicated that it possessed an expectorant effect. However, in modern times, it is commonly used as a tocolytic agent. In this study, the components of AMR that are responsible for its expectorant and tocolytic effects were evaluated in order to clarify the differences in its application between ancient and modern times. A decoction of AMR was separated into five fractions, namely, volatile oil (VO), petroleum ether (PE), alcohol eluate from macroporous resin (AE), water eluate from macroporous resin (WE), and polysaccharides (PS), using various separation methods. The expectorant experiment indicated that the VO fraction, which mainly contains atractylone, produced an obvious expectorant effect. The experiment that assessed the irritability of uterine smooth muscle (USM) showed that the PE, which is mainly composed of atractylenolides, and the PS, which is mainly composed of inulin-type polysaccharides, were the active fractions for tocolysis, but the VO fraction had the opposite action. These data suggested that volatile oils are the key components responsible for the usage change of AMR in both ancient and current usage.

[Study on method and its optimization of improving seed germination of Astragalus membranaceus as gansu traditional medicinal herb].

OBJECTIVE: To break the hard testa and improve seed germination situation of Astragalus membranaceus var. mongholicus, in order to solve the problems of low success rate of seed germination and seedling. METHODS: Longxi Astragalus membranaceus var. mongholicus seed was treated by soaking seed with 75% alcohol and concentrated sulfuric acid, warm-water incubating, grinding and comprehensive treating with warm-water incubating, grinding and sand culture. Its seed germination situation was evaluated by germination potential, germination rate and germination index. RESULTS: Different processing methods significantly improved seed germination with different effect. Comprehensive treatment with warm-water incubating, grinding and sand culture was the best one on Astragalus membranaceus var. mongholicus seed germination. Its germination potential, germination rate and germination index was 66.04%, 87.70% and 1.34,respectively. CONCLUSION: Comprehensive treatment with warm-water incubating, grinding and sand culture is an economic and effective processing method, which is suitable for actual production.

Triterpene alcohols and sterols from rice bran lower postprandial glucose-dependent insulinotropic polypeptide release and prevent diet-induced obesity in mice.

Obesity is now a worldwide health problem. Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone that is secreted following the ingestion of food and modulates energy metabolism. Previous studies reported that lowering diet-induced GIP secretion improved energy homeostasis in animals and humans, and attenuated diet-induced obesity in mice. Therefore, food-derived GIP regulators may be used in the development of foods that prevent obesity. Rice bran oil and its components are known to have beneficial effects on health. Therefore, the aim of the present study was to clarify the effects of the oil-soluble components of rice bran on postprandial GIP secretion and obesity in mice. Triterpene alcohols [cycloartenol (CA) and 24-methylene cycloartanol (24Me)], ß-sitosterol, and campesterol decreased the diet-induced secretion of GIP in C57BL/6J mice. Mice fed a high-fat diet supplemented with a triterpene alcohol and sterol preparation (TASP) from rice bran for 23 wk gained less weight than control mice. Indirect calorimetry revealed that fat utilization was higher in TASP-fed mice than in control mice. Fatty acid oxidation-related gene expression in the muscles of mice fed a TASP-supplemented diet was enhanced, whereas fatty acid synthesis-related gene expression in the liver was suppressed. The treatment of HepG2 cells with CA and 24Me decreased the gene expression of sterol regulatory element-binding protein (SREBP)-1c. In conclusion, we clarified for the first time that triterpene alcohols and sterols from rice bran prevented diet-induced obesity by increasing fatty acid oxidation in muscles and decreasing fatty acid synthesis in the liver through GIP-dependent and GIP-independent mechanisms.

Effect of wheatgrass on membrane fatty acid composition during hepatotoxicity induced by alcohol and heated PUFA.

Alcoholism is a broad term used for problems related to alcohol, medically considered as disease, specifically an addictive illness, abuse, and dependence. It is the major cause of liver disease in western countries. Alcoholic liver disease encompasses the hepatic alterations leading to fatty liver, hepatitis, and fibrosis or cirrhosis. Fried food items prepared with repeatedly heated polyunsaturated fatty acid (PUFA) exacerbate the disturbances induced by alcohol. The use of herbs to treat diseases is almost universal. Wheatgrass (WG) is used as a supplemental nutrition because of its unique curative properties. As it has antioxidant property, it prevents cancer, diabetes, and acts as liver cleanser. The present study was undertaken to evaluate the efficacy of WG on preserving membrane integrity in liver damage induced by alcohol and heated PUFA (ΔPUFA).The rats were divided into four groups. The animals in group 1 served as normal (standard diet), group 2 served as hepatotoxic (alcohol + ΔPUFA), group 3 served as treated (alcohol + ΔPUFA + WG), and group 4 served as WG control. The compositions of membrane fatty acid, total phospholipids, phospholipase A, C (PLA and PLC) were analyzed in liver to evaluate the effects of WG. Changes in fatty acid composition, decrease in phospholipids levels, and increase in PLA, PLC were observed in the diseased group. Restoration effect was seen in WG-treated rats. Histopathological observations were in correlation with the biochemical parameters. From the results obtained, we conclude that WG effectively protects the liver against alcohol and ΔPUFA-induced changes in fatty acid composition and preserves membrane integrity.

Concentration-dependent antagonistic persuasion of SDS and naphthalene derivatives on the fibrillation of stem bromelain.

Sodium dodecyl sulfate, a biological membrane mimetic, can be used to study the conversion of globular proteins into amyloid fibrils in vitro. Using multiple approaches, the effect of SDS was examined on stem bromelain (SB), a widely recognized therapeutic protein. SB is known to exist as a partially folded intermediate at pH 2.0, situation also encountered in the gastrointestinal tract (its site of absorption). In the presence of sub-micellar SDS concentration (500-1000 µM), this intermediate was found to exhibit great propensity to form large-sized ß-sheeted aggregates with fibrillar morphology, the hall marks of amyloid structure. We also observed inhibition of fibrillation by two naphthalene-based compounds, ANS and bis-ANS. While bis-ANS significantly inhibited fibril formation at 50 µM, ANS did so at relatively higher concentration (400 µM). Alcohols, but not salts, were found to weaken the inhibitory action of these compounds suggesting the possible involvement of hydrophobic interactions in their binding to protein. Besides, isothermal titration calorimetry and molecular docking studies suggested that inhibition of fibrillation by these naphthalene derivatives is mediated not just through hydrophobic forces, but also by disruption of π-π interactions between the aromatic residues together with the inter-polypeptide chain repulsion among negatively charged ANS/bis-ANS bound SB.

Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ulcers.

Gastroprotective mechanism of peganine hydrochloride isolated from Peganum harmala seeds was investigated. Peganine hydrochloride was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of peganine was observed against CRU (50.0%), AS (58.5%), AL (89.41%) and PL (62.50%) induced ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.45% protection against CRU, 49.97% against AS and 69.42% against PL model. Sucralfate, another reference drug (500mg/kg, p.o.) showed 62.50% protection in AL induced ulcer model. Peganine significantly reduced free acidity (33.38%), total acidity (38.09%) and upregulated mucin secretion by 67.91%, respectively. Further, peagnine significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 73.47µg/ml as compared to the IC50 value of omeprazole (30.24µg/ml) confirming its anti-secretory activity.

Arbortristoside-A and 7-O-trans-cinnamoyl-6ß-hydroxyloganin isolated from Nyctanthes arbortristis possess anti-ulcerogenic and ulcer-healing properties.

Nyctanthes arbortristis Linn (Oleaceae) is widely distributed in sub-Himalayan regions and southwards to Godavari, India commonly known as Harsingar and Night Jasmine. In continuation of our drug discovery program on Indian medicinal plants, we isolated arbortristoside-A (AT) and 7-O-trans-cinnamoyl-6ß-hydroxyloganin (6-HL) from the seeds of N. arbortristis. AT and 6-HL exhibited anti ulcer activity in experimentally induced ulcer models including cold restraint stress (CRU), alcohol (AL), pylorus ligation-induced gastric ulcer (PL) models and they also showed ulcer healing effect in chronic acetic acid-induced ulcer model (AC).