Neuroinflammation and Acetylcholinesterase Inhibitory Potentials of a Spiroketal-Enol Ether Polyyne Isolated from Artemisia pallens Wall. ex DC.

Artemisia pallens Wall. ex DC (Asteraceae) is cultivated for the production of high-value essential oil from its aerial biomass. In this study, the chemical composition of the root (crop-residue) essential oil was investigated for the first time, using column-chromatography, GC-FID, GC-MS, LC-QTOF, and NMR techniques, which led to the identification of twenty constituents, with isolation of (E)-2-(2',4'-hexadiynylidene)-1,6-dioxaspiro [4.5]dec-3-ene (D6). The D6 was evaluated in vitro for neuroinflammation and acetylcholinesterase inhibitory potential. It showed inhibition of neuroinflammation in a concentration-dependent manner with significant inhibition of pro-inflammatory cytokines (TNF-α and IL-6) in LPS-stimulated BV2 microglial cells. D6 did not have any significant effect on the viability of the cells at the therapeutic concentrations. D6 also has shown acetylcholinesterase inhibitory potential (51.90±1.19 %) at the concentration of log 106  nM. The results showed that D6 has a potential role in the resolution of neuroinflammation, and its acetylcholinesterase inhibitory potential directs further investigation of its role in the management of Alzheimer's disease-related pathogenesis.

Phytochemical characterization, in vivo and in vitro biological activities of Atriplex lindleyi Moq. subsp. inflata.

ETHNOPHARMACOLOGICAL RELEVANCE: Atriplex lindleyi Moq. subsp. inflata from Algeria is known for its traditional use for therapeutic properties. AIM OF THE STUDY: We analysed quantitatively and qualitatively the infusion and diethyl ether, n-butanol and ethereal extracts of A. lindleyi, as well as assessed their acute toxicity, anti-inflammatory, antinociceptive and antioxidant activities. MATERIALS AND METHODS: The total phenolic and flavonoid contents were quantified. The anti-inflammatory effect was assessed using a carrageenan-induced paw oedema assay and the antinociceptive effect was evaluated using an acetic acid-induced writhing method. In addition, antioxidant activity was examined by three tests: DPPH, reducing power and phenanthroline assays. RESULTS: The quantity of total phenols in the roots of A. lindleyi was larger than in the aerial parts, while the amounts of total flavonoids were larger in the aerial parts than in the roots. The HPLC profiles allowed us to identify 32 compounds belonging to the phenolic acid and flavonoid classes. Intraperitoneal administration of the infusions and phenolic extracts in mice did not cause any symptoms of toxicity or mortality. Results revealed that the aerial parts and roots of A. lindleyi had potential anti-inflammatory and antinociceptive activities and were higher than diclofenac and paracetamol, respectively. The diethyl ether extract (DEE) of aerial parts and roots showed the greatest antioxidant activity in comparison to the other tested extracts. CONCLUSION: The phenolic composition attempted to be identified by HPLC confers this plant's pharmacological potential. The antioxidant potential may be due to active ingredients, including ascorbic acid, in the two studied parts of A. lindleyi, which is a bioactive molecule with strong antioxidant properties. Also, detecting salicylic acid, the active antinociceptive ingredient of aspirin, gallic and ferulic acids may justify this subspecies' antinociceptive and anti-inflammatory potentials.

Protein S-palmitoylation is markedly inhibited by 4″-alkyl ether lipophilic derivatives of EGCG, the major green tea polyphenol: In vitro and in silico studies.

S-palmitoylation is a dynamic lipid-based protein post-translational modification facilitated by a family of protein acyltransferases (PATs) commonly known as DHHC-PATs or DHHCs. It is the only lipid modification that is reversible, and this very fact uniquely qualifies it for therapeutic interventions through the development of DHHC inhibitors. Herein, we report that 4″-alkyl ether lipophilic derivatives of EGCG can effectively inhibit protein S-palmitoylation in vitro. With the help of metabolic labeling followed by copper(I)-catalyzed azide-alkyne cycloaddition Click reaction, we demonstrate that 4″-C14 EGCG and 4″-C16 EGCG markedly inhibited S-palmitoylation in various mammalian cells including HEK 293T, HeLa, and MCF-7 using both in gel fluorescence as well as confocal microscopy. Further, these EGCG derivatives were able to attenuate the S-palmitoylation to the basal level in DHHC3-overexpressed cells, suggesting that they are plausibly targeting DHHCs. Confocal microscopy data qualitatively reflected spatial and temporal distribution of S-palmitoylated proteins in different sub-cellular compartments and the inhibitory effects of 4″-C14 EGCG and 4″-C16 EGCG were clearly observed in the native cellular environment. Our findings were further substantiated by in silico analysis which revealed promising binding affinity and interactions of 4″-C14 EGCG and 4″-C16 EGCG with key amino acid residues present in the hydrophobic cleft of the DHHC20 enzyme. We also demonstrated the successful inhibition of S-palmitoylation of GAPDH by 4″-C16 EGCG. Taken together, our in vitro and in silico data strongly suggest that 4″-C14 EGCG and 4″-C16 EGCG can act as potent inhibitors for S-palmitoylation and can be employed as a complementary tool to investigate S-palmitoylation.

The impact of PEEK pretreatment using H2SO4, riboflavin, and aluminum trioxide on the extrusion bond strength to canal dentin luted with Polymethyl methacrylate and resin-based composite cement.

OBJECTIVE: To evaluate the effects of various surface pretreatment methods, including H2SO4, Riboflavin, and Al2O3, as well as different luting cement types, namely Methyl Methacrylate based Cement (MMBC) and composite-based cement (CBC), on the extrusion bond strength (EBS) of poly-ether-ether-ketone (PEEK) posts bonded to canal dentin. MATERIALS AND METHODS: This study involved 120 single-rooted human premolar teeth that underwent endodontic treatment. Following root canal preparation, PEEK posts were fabricated from PEEK blanks using a CAD-CAM system, resulting in a total of 120 posts. The posts were randomly assigned to one of four groups based on their post-surface conditioning: Group A H2SO4, Group B RF, Group C Al2O3, and Group D (NC), each consisting of 30 posts. Within each group, there were two subgroups based on the type of luting cement used for bonding. Subgroups A1, B1, C1, and D1 (n=15 each) utilized CBC, while Subgroups A2, B2, C2, and D2 (n=15 each) used MMBC.The bond strength between the PEEK posts and root dentin was assessed using a universal testing machine, and the failure modes were examined under a stereomicroscope. Statistical analysis, including one-way analysis of variance (ANOVA) and Tukey's Post Hoc test with a significance level of p=0.05, was performed to analyze the data and evaluate the effects of surface treatment and luting cement type on the bond strength. RESULTS: Group B2, which underwent RF conditioning followed by Super-Bond C&B cement application, exhibited the highest bond strength scores at the coronal section (9.57±0.67 MPa). On the other hand, Group D1, which had no conditioning (NC) and used Panavia® V5 cement, showed the lowest EBS at the apical third (2.39±0.72 MPa). The overall results indicate that the different conditioning regimens and luting cement types did not significantly influence the bond strength of PEEK posts to root dentin (p>0.05). CONCLUSIONS: Riboflavin activated by photodynamic therapy (PDT) and H2SO4 can be effective surface conditioners for PEEK posts. These treatments have shown potential for enhancing the bond strength between PEEK and resin cement. Additionally, the study revealed that MMA-based cement outperformed composite-based cement in terms of bond integrity with PEEK posts.

Poly-Ether Ether-Ketone Post Conditioned with Sulfuric Acid, Rose Bengal Activated by Photodynamic Therapy and Sandblasting on Pushout Bond Strength to Radicular Dentin Luted with Methyl Methacrylate and Composite-Based Cement.

Objective: Assessment of post surface conditioners [sulfuric acid (SA), Rose Bengal (RB), and sandblasting (SB)] and different luting cements [methyl methacrylate (MMA)-based cement and composite-based cement] on pushout bond strength (PBS) of poly-ether ether-ketone (PEEK) post bonded to canal dentin. Materials and methods: Endodontic treatment was performed on 120 single-rooted human premolar teeth. The preparation of the post space was performed and 4 mm of gutta-percha was retained in the apical region of the root. One hundred and twenty PEEK posts were fabricated from a PEEK blank utilizing a Computer aided design-Computer aided manufacture (CAD-CAM) system. The PEEK posts were allocated randomly into four groups based on post surface conditioning (n = 30). Group A: SA, Group B: RB, Group C: SB, and Group D: No conditioning (NC). Each group was further divided into two subgroups based on the luting cement used for bonding (n = 15). Group A1, B1, C1, and D1 specimens were cemented using composite-based resin cement. However, Group A2, B2, C2, and D2 posts were luted with MMA-based resin cement. PBS assessment using a universal testing machine was performed. Failure modes were analyzed under a stereomicroscope. The data relating to the effects of surface treatment and luting types of cement were analyzed using one-way analysis of variance (ANOVA) and Tukey's post hoc test (p = 0.05). Results: Coronal section of Group B2: RB+Super-Bond C&B [9.61 ± 0.75 megapascals (MPa)] displayed the highest bond scores of PEEK after root dentin. Whereas it was also discovered that Group D1: NC+Panavia®V5 (2.05 ± 0.72 MPa) presented the lowest PBS scores. Intergroup comparison analysis revealed that Group A2: SA+Super-Bond C&B and Group B2: RB+Super-Bond C&B displayed no significant difference in their bond scores. Conclusions: RB and SA possess the potential to be used as a PEEK post conditioner. MMA-based cement displayed better performance than composite-based cement.

Antioxidant and Anti-Inflammatory Activities of Phenolic Acid-Rich Extract from Hairy Roots of Dracocephalum moldavica.

This study evaluates the antioxidant properties and anti-inflammatory potential of polyphenolic acid-rich fractions of 80% methanolic extract from the hairy roots of Dracocephalum moldavica. The fractionation of the crude extract yielded the following: a diethyl ether fraction rich in caffeic acid (DM1) (25.85 mg/g DWE), an n-butyl fraction rich in rosmarinic acid (DM3) (43.94 mg/g DWE) and a water residue rich in salvianolic acid B (DM4) (51.46 mg/g DWE). The content of these compounds was determined using high-performance liquid chromatography (HPLC). Their antioxidant activity was evaluated based on DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt) and FRAP assays. The anti-inflammatory activity of the fractions was determined by their effect on nuclear factor kappa-B (NF-κB) activation and interleukin-1ß (IL-1ß) production in LPS E. coli stimulated monocytes. The level of pro-inflammatory IL-1ß in cells was measured using ELISA. The activation of NF-κB in THP1-Blue™ cells, resulting in the secretion of SEAP (secreted embryonic alkaline phosphatase), was detected spectrophotometrically using Quanti-Blue reagent. Among the tested fractions, the diethyl ether fraction (DM1) showed the highest antioxidant potential, with an EC50 value of 15.41 µg/mL in the DPPH assay and 11.47 µg/mL in ABTS and a reduction potential of 10.9 mM Fe(II)/g DWE in FRAP. DM1 at a concentration of 10 mg/mL also efficiently reduced LPS-induced SEAP secretion (53% inhibition) and IL-1ß production (47% inhibition) without affecting the normal growth of L929 fibroblast cells.

Chemical Profile and Biological Potential of Hornodermoporus martius (Agaricomycetes) from Paraguay.

To further knowledge of the biological activity of native neotropical fungal species, this study aimed to determine the chemical composition and microbiological activity of Hornodermoporus martius. Ethanol, hexane, diethyl ether, and ethyl acetate fractions and the water residue were analyzed and resulted in a total phenolic compound content between 13 and 63 mg of gallic acid equivalents per gram of crude extract. The total antioxidants ranged between 3 and 19 mg of ascorbic acid equivalents per gram of crude extract, and the percentage of antioxidant activity was determined to be between 6 and 25%. A preliminary profile of compounds is provided for the first time for the species; the results from the nonpolar fraction showcased the presence of saturated and unsaturated acids, fatty alcohol, sterols, and cis-vaccenic acid. Our findings also revealed antimicrobial properties from compounds within the hexane and diethyl ether fractions at concentrations of 1 mg mL-1, which inhibited the growth of certain gram-positive and gram-negative bacteria. For the first time in academic literature, our work analyzed and documented the chemical characteristics and microbial properties of H. martius, suggesting potential for medicinal applications.

Solvent-like bis (2-chloro-1-methylethyl) ether occurrence in drinking water: Multidimensional risk assessment integrated health and aesthetic aspects.

Bis (2-chloro-1-methylethyl) ether (DCIP), one U.S. Environmental Protection Agency priority pollutant, could pose health and/or odor risk in water environment. In this study, odor characteristics, occurrence and source of DCIP in drinking waters of China were investigated based on sensory analysis and a nation-wide investigation covering 140 drinking water treatment plants. Then multi-risk integrated health and aesthetic aspects through oral and inhalation (showering) exposure by drinking water were first estimated. Sensory evaluation showed DCIP exhibited "solvent-like" odor with thresholds of 34.8 ng/L in air and 142.0 ng/L in water. DCIP was detected at comparable concentrations in raw and finished waters (<1280 ng/L) and was by-product from industrial production of epichlorohydrin/propylene oxide. Lifetime Average Daily Dose through oral exposure was 0-36.65 ng/day/kg, corresponding to odor activity values of 0-8.4 and hazard quotients of far < 1, indicating drinking tap water might cause odor issues rather than significant health hazard. The proportion of sensitive population to DCIP's odor was 6.1%. In contrast, residents rarely detect DCIP's odor by inhalation. The presence in drinking water as industrial by-product, poor removal using conventional water treatment and potential to be T&O issues, indicates urgent demand for pollutant source control to protect DCIP from entering source waters.

Melanogenesis Inhibitory Activity, Chemical Components and Molecular Docking Studies of Prunus cerasoides Buch.-Ham. D. Don. Flowers.

Safe depigmenting agents are currently increasing in the cosmetic or pharmaceutical industry because various compounds have been found to have undesirable side effects. Therefore, the present study aimed to investigate the melanogenesis inhibitory effects of Prunus cerasoides Buch. -Ham. D. Don. flower extracts and their molecular mechanism in B16F10 mouse melanoma cells. Moreover, we also examined phenolic and flavonoid contents, antioxidant activity, chemical constituents of potential extracts, and molecular docking. The highest phenolic and flavonoid contents with the greatest scavenging activity were found in the butanol extract of the P. cerasoides flower compared to other extracts. From all extracts, only crude, diethyl ether, and butanol extracts showed an inhibition of mushroom tyrosinase activity, cellular tyrosinase activity, and melanin content as well as the downregulation of the gene expression of the microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) in α-MSH-stimulated B16F10 cells. Based on the molecular docking study, n-hexadecanoic acid, heptadecanoic acid, octadecanoic acid, 9,12-octadecadienoic acid, 9,12,15-octadecanoic acid, and eicosanoic acid might show an inhibitory effect against tyrosinase and MITF. In conclusion, this finding demonstrates that both the diethyl ether and butanol extracts of the P. cerasoides flower can effectively reduce tyrosinase activity and melanin synthesis through the downregulation of the melanogenic gene expression in B16F10 cells and through the molecular docking study. Taken together, the diethyl ether and butanol extracts of the P. cerasoides flower could be an anti-melanogenic ingredient for hyperpigmentary or melasma treatment.

Virtual screening of DrugBank database for hERG blockers using topological Laplacian-assisted AI models.

The human ether-a-go-go (hERG) potassium channel (Kv11.1) plays a critical role in mediating cardiac action potential. The blockade of this ion channel can potentially lead fatal disorder and/or long QT syndrome. Many drugs have been withdrawn because of their serious hERG-cardiotoxicity. It is crucial to assess the hERG blockade activity in the early stage of drug discovery. We are particularly interested in the hERG-cardiotoxicity of compounds collected in the DrugBank database considering that many DrugBank compounds have been approved for therapeutic treatments or have high potential to become drugs. Machine learning-based in silico tools offer a rapid and economical platform to virtually screen DrugBank compounds. We design accurate and robust classifiers for blockers/non-blockers and then build regressors to quantitatively analyze the binding potency of the DrugBank compounds on the hERG channel. Molecular sequences are embedded with two natural language processing (NLP) methods, namely, autoencoder and transformer. Complementary three-dimensional (3D) molecular structures are embedded with two advanced mathematical approaches, i.e., topological Laplacians and algebraic graphs. With our state-of-the-art tools, we reveal that 227 out of the 8641 DrugBank compounds are potential hERG blockers, suggesting serious drug safety problems. Our predictions provide guidance for the further experimental interrogation of DrugBank compounds' hERG-cardiotoxicity.

As a novel anticancer candidate, ether extract of Dendrobium nobile overstimulates cellular protein biosynthesis to induce cell stress and autophagy.

Increasing data has confirmed the potential anticancer properties of Dendrobium, a traditional Chinese herb. However, most anticancer compositions from the plant of Dendrobium were usually extracted by high polar solvent, while weak polar compositions with excellent anticancer activity remained largely unexplored. In this study, the differences between ether extract and ethanol extract of Dendrobium nobile Lindl. on chemical components and anticancer activities were investigated, as well as the anticancer mechanisms among different extracts. The results demonstrated that the ether extract exhibited a stronger anticancer effect than ethanol extract, and its anticancer effect was mainly due to weak polar compounds rather than polysaccharides and alkaloids. Quantitative proteomics suggested that the ether extract significantly stimulated the over-expression of immature proteins, the endoplasmic reticulum stress and unfolded protein response were subsequently induced, the intracellular reactive oxygen species level was seriously elevated, and oxidative stress occurred in the meanwhile. Eventually, autophagy and apoptosis were activated to cause cell death. Our findings demonstrate that the ether extract of D. nobile is a potential candidate for anticancer drug development, and that future research on anticancer drugs derived from medicinal plants should also concentrate on weak polar compounds.

Antioxidant, antibacterial, and antileishmanial potential of Micromeria nervosa extracts and molecular mechanism of action of the bioactive compound.

AIMS: This study aimed to determine the antibacterial and antileishmanial potential of Micromeria nervosa extracts. The identification of the antileishmanial compound and the study of its molecular mechanism of action have also been undertaken. METHODS AND RESULTS: Ethanol extract showed high polyphenol content and diethyl ether extract exhibited high DPPH scavenging and low beta-carotene bleaching activity (IC50 = 13.04 ± 0.99 and 200.18 ± 3.32 µg mL-1, respectively). However, diethyl ether extract displayed high antibacterial activity against Gram-positive strains including methicillin-resistant Staphylococcus aureus (MIC = 31.25 µg mL-1), Staph. aureus ATCC6538 (MIC = 62.5 µg mL-1), and Listeria monocytogenes ATCC 19115 (MIC = 125 µg mL-1), as well as high antileishmanial activity against the promastigote forms of L. infantum and L. major (IC50 = 11.45 and 14.53 µg mL-1, respectively). The active compound was purified using bioassay-guided fractionation and thin layer chromatography, and identified as ursolic acid using high-performance liquid chromatography coupled with a photodiode array and mass spectrometry. The purified compound was strongly inhibitory against the promastigote and amastigote forms of L. infantum and L. major (IC50 = 5.87 and 6.95 µg mL-1 versus 9.56 and 10. 68 µg mL-1, respectively) without overt cytotoxicity against Raw 264.7 macrophage cells (SI = 13.53 and 11.43, respectively). The commercial compound (ursolic acid) showed similar activity against amastigotes and promastigotes forms of L. infantum and L. major. Moreover, its molecular mode of action against leishmaniasis seems to involve the expression of the ODC and SPS genes involved in thiol pathway. CONCLUSION: Extracts of M. nervosa can be considered as a potential alternative to antimicrobial and antileishmanial drugs.

A Discovery-Based Metabolomic Approach Using UPLC-Q-TOF-MS/MS Reveals Potential Antimalarial Compounds Present in Artemisia annua L.

In 1972, Nobel laureate Youyou Tu's research team conducted clinical trials on the dried material of Artemisia annua L. from Beijing extracted by ether and then treated with alkali (called "ether neutral dry"), which showed that artemisinin was not the only antimalarial component contained. The biosynthesis of sesquiterpenoids in A. annua has increased exponentially after unremitting cultivation efforts, and the plant resources are now quite different from those in the 1970s. In consideration of emerging artemisinin resistance, it is of great theoretical and practical value to further study the antimalarial activity of A. annua and explore its causes. The purpose of this study is to clarify scientific questions, such as "What ingredients are synergistic with artemisinin in A. annua?", and "Are there non-artemisinin antimalarial ingredients in A. annua?". In this paper, Beijing wild A. annua was used as a control and two representative cultivation species of A. annua were selected to evaluate the antimalarial activity of the herbal medicine. The antimalarial activity of different extracts on mice was studied using the Peters' four-day suppressive test. UPLC-Q-TOF-MS was used to obtain mass spectrum data for all samples, and a UNIFI platform was used for identification. A multivariate statistical method was used to screen the different compounds with positive correlations. The antimalarial activity of different components from the ether extract and alkali treatments was determined and antimalarial components other than artemisinin were obtained. A total of 24 flavonoids, 68 sesquiterpenoids and 21 other compounds were identified. Compounds associated with differential antimalarial activity were identified. The material basis for the antimalarial activity of A. annua was clarified. The antimalarial components of A. annua include two categories: first, artemisinin and non-artemisinin antimalarial active components, of which the non-artemisinin antimalarial active components may include 5α-hydroperoxy-eudesma-4(15),11-diene; second, several antimalarial synergistic ingredients in A. annua, including arteanniun B, arteanniun B analogues and polymethoxy flavonoids.

LC-PDA-MS and GC-MS Analysis of Scorzonera hispanica Seeds and Their Effects on Human Breast Cancer Cell Lines.

Scorzonera hispanica is an herbaceous perennial cultivated in Central and Southern Europe. This study aimed to qualitatively and quantitatively evaluate the composition of oil, extracts, and fractions (SH1-SH12) obtained from S. hispanica seeds. Furthermore, an evaluation of biological activities in breast cancer cell lines was also performed. GC-MS analysis revealed that the primary components of the seed oil (SH12) were fatty acids and ß-sitosterol. In the evaluation of extracts (SH1-SH3, SH8-SH10) and fractions (SH4-SH7, SH11) composition, the presence of apigenin, derivatives of p-coumaric and caffeic acids, was reported. In the biological assays, methanolic extract (SH1), diethyl ether (SH4), and chloroform (SH11) fractions exhibited cytotoxicity toward cells. The highest activity was observed for fatty acids- and 3,4-dimethoxycinnamate-rich SH11 (IC50: 399.18 µg/mL for MCF-7, 781.26 µg/mL for MDA-MB-231). SH11 was also observed to induce apoptosis in MCF-7 cells (52.4%). SH1, SH4, and SH11 attenuate signaling pathways and affect the expression of apoptosis-, autophagy-, and inflammation-related proteins. SH12 was non-toxic toward either cancer or normal cell lines in concentrations up to 1 mg/mL. The results suggest that S. hispanica seeds exhibit a wide range of potential uses as a source of oil and bioactive compounds for complementary therapy of breast cancer.

Ether lipid deficiency disrupts lipid homeostasis leading to ferroptosis sensitivity.

Ferroptosis is an iron-dependent form of regulated cell death associated with uncontrolled membrane lipid peroxidation and destruction. Previously, we showed that dietary dihomo-gamma-linolenic acid (DGLA; 20: 3(n-6)) triggers ferroptosis in the germ cells of the model organism, Caenorhabditis elegans. We also demonstrated that ether lipid-deficient mutant strains are sensitive to DGLA-induced ferroptosis, suggesting a protective role for ether lipids. The vinyl ether bond unique to plasmalogen lipids has been hypothesized to function as an antioxidant, but this has not been tested in animal models. In this study, we used C. elegans mutants to test the hypothesis that the vinyl ether bond in plasmalogens acts as an antioxidant to protect against germ cell ferroptosis as well as to protect from whole-body tert-butyl hydroperoxide (TBHP)-induced oxidative stress. We found no role for plasmalogens in either process. Instead, we demonstrate that ether lipid-deficiency disrupts lipid homeostasis in C. elegans, leading to altered ratios of saturated and monounsaturated fatty acid (MUFA) content in cellular membranes. We demonstrate that ferroptosis sensitivity in both wild type and ether-lipid deficient mutants can be rescued in several ways that change the relative abundance of saturated fats, MUFAs and specific polyunsaturated fatty acids (PUFAs). Specifically, we reduced ferroptosis sensitivity by (1) using mutant strains unable to synthesize DGLA, (2) using a strain carrying a gain-of-function mutation in the transcriptional mediator MDT-15, or (3) by dietary supplementation of MUFAs. Furthermore, our studies reveal important differences in how dietary lipids influence germ cell ferroptosis versus whole-body peroxide-induced oxidative stress. These studies highlight a potentially beneficial role for endogenous and dietary MUFAs in the prevention of ferroptosis.

Hemimycale Arabica Induced Non-Cytotoxic Anti-Migratory Activity in Hepatocellular Carcinoma In Vitro.

OBJECTIVE: In this work, we represented new non-cytotoxic treatments to avoid serious side effects of current used cytotoxic anticancer drugs. These treatments can compensate in finding convenient treatment for each individual case using a single agent from marine sponge Hemimycale arabica. METHODS: The ethanol extract was partitioned by cold sequential liquid-liquid extraction to afford petroleum ether, diethyl ether, dichloromethane and ethyl acetate fractions. Chemical composition of H. arabica was performed by gas-liquid chromatography and gas chromatography-mass spectroscopy. Anticancer activity was evaluated by means of cytotoxicity, apoptosis induction, tumor cell migration inhibition and expression analysis of proliferation and migration-related genes. RESULTS: Our results revealed that all treatments were non-cytotoxic except for dichloromethane fraction which exhibited moderate cytotoxic activity. Caspase-independent apoptosis was induced by total ethanol and dichloromethane fractions while ethyl acetate fraction induces caspase-dependent apoptosis. All treatments inhibited matrix metalloproteinase-independent migration. Petroleum ether and dichloromethane inhibited migration through the down-regulation of FGF and it could be used as anticancer therapy for VEGF-resistance patients. While ethanol inhibited tumor cell migration through down-regulation of all tested genes expression. Ether and ethyl acetate fractions exerted anti-migratory activity without affecting the tested genes. All resuls were statistically significant at p˂0.05. CONCLUSION: Total ethanol extract is a promising non-cytotoxic anticancer agent because of its powerful apoptosis induction and capability to block tumor cell migration. Petroleum ether and ether fractions area weak non-cytotoxic anti-migratory agents. Dichloromethane could be a moderate cytotoxic anti-migratory agent induced caspase-independent apoptosis. It could be used in anticancer therapy for VEGF-resistance patients through downregulation of FGF. Ethyl acetate fraction considered a non-cytotoxic agent exerting moderate anti-migratory activity. The new sponge-derived treatments can solve different resistance problems to find a convenient treatment for each individual case using a single agent.

Ether lipid transfer across the blood-brain and placental barriers does not improve by inactivation of the most abundant ABC transporters.

Phospholipid transport from the periphery to the brain is an understudied topic. When certain lipid species are deficient due to impaired synthesis, though, transfer across the blood-brain barrier is essential for replenishing lipids in the brain. For example, the deficiency in plasmalogens, the most abundant ether lipids in mammals, has detrimental effects on the brain, which is a major issue in inherited peroxisomal disorders but also contributes to more common disorders like Alzheimer's disease. Oral administration of alkylglycerols like batyl alcohol, which carry a pre-formed ether bond, enables replenishment of ether lipids in various peripheral tissues. However, plasmalogen deficiency in the brain cannot be overcome by this approach. Here, we tried to increase cerebral plasmalogen uptake by modulating the efflux transport across the blood-brain barrier. We hypothesized, based on previous literature, that at least some ether lipid species readily enter endothelial cells of the barrier through the transporter MFSD2A but are re-exported by ATP-binding cassette (ABC) transporters. By crossbreeding Mdr1a-/-/Mdr1b-/-/Bcrp-/- and ether lipid-deficient Gnpat-/- mice as well as pharmacological inhibition with MK-571 to inactivate the major ABC transporters at the blood-brain barrier, we evaluated the potential of combined ABC transporter inhibition and oral batyl alcohol administration for the treatment of plasmalogen deficiency. We found that even in the absence of the most abundant ABC transporters, batyl alcohol supplementation did not restore plasmalogen levels in the brain, despite the presence of a wide spectrum of ether lipid subspecies in the plasma as demonstrated by lipidomic analysis. Surprisingly, batyl alcohol treatment of pregnant Gnpat+/- dams had beneficial effects on the plasmalogen levels of Gnpat-/- offspring with defective ether lipid biosynthesis, independently of ABC transporter status at the placental barrier. Our results underline the autonomy of brain lipid homeostasis and indicate that peripheral supplementation of ether lipids is not sufficient to supply the brain with larger amounts of plasmalogens. Yet, the findings suggest that alkylglycerol treatment during pregnancy may pose a viable option to ameliorate some of the severe developmental defects of inborn ether lipid deficiency.

Phytochemical Analysis, Acute Toxicity, as well as Antihyperglycemic and Antidiabetic Activities of Corchorus olitorius L. Leaf Extracts.

Backgroundand Aim. Diabetes mellitus is a metabolic disorder that has no known cure with continuous endeavors to find a therapy for the condition. According to some studies, traditional leafy vegetables could prevent and manage diabetes by modifying the carbohydrate and lipid metabolism. In this study, a phytochemical analysis, acute toxicity, as well as antihyperglycemic and antidiabetic activity testing of the methanolic, diethyl ether, and aqueous leaf extracts of Corchorus olitorius L. was performed. Materials and Methods. Methanolic, diethyl ether, and aqueous leaf extracts of Corchorus olitorius L. were prepared by serial extraction. Phytochemical analysis was performed following standard methods. 52 mice were separated into 13 groups (A-M) of 4 and received extracts' doses ranging from 1000 mg/kg to 5000 mg/kg for the acute toxicity testing. For the antihyperglycemic and antidiabetic activities testing, 48 rats were divided into 8 groups of 6 and received 500 mg/kg of each extract. 10 mg/kg of glibenclamide and distilled water were used as controls. Data were analyzed using Prism GraphPad version 8.0.2 (263). Results. Phytochemical analysis revealed the presence of alkaloids, reducing sugars, saponins, and terpenoids. There were no acute toxicity signs observed in this study. Corchorus olitorius L. extracts demonstrated moderate antihyperglycemic and antidiabetic activities. The methanolic extract exhibited the highest degree of antihyperglycemic activity. However, there was no statistically significant difference between the extracts and the negative control (p > 0.05), but with glibenclamide (p < 0.01). Conclusion. Corchorus olitorius L. is a safe and potential postprandial antidiabetic vegetable that could minimize the rise in blood glucose after a meal. We therefore recommend further investigations into the antidiabetic properties of the vegetable using purified extracts.

Antimicrobial, antioxidant, antiviral activity, and gas chromatographic analysis of Varanus griseus oil extracts.

There is an urgent need to develop natural antimicrobials for the control of rapidly mutating drug-resistant bacteria and poultry viruses. Five extracts were prepared using diethyl ether, ethyl acetate, methanol, 1-butanol and n-hexane from abdominal fats of Varanus griseus locally known as Indian desert monitor. Antibacterial, antioxidant and antiviral activities from oil extracts were done through disc diffusion method, stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay and in ovo antiviral assay, respectively. The gas chromatography mass spectrometry (GC-MS) analyses were used to determine principal active compounds and chemical profile of each oil extract. n-Hexane extract showed clear zones of inhibition (ZOI) against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae (12 ± 0.5 mm, 9 ± 0.5 mm, and 9 ± 0.5 mm) while diethyl ether extract exhibited significant antibacterial activity (11 ± 0.5 mm) against Proteus vulgaris only. In case of drug-resistant strains, methanol extract was active (6 ± 0.5 mm) against Staphylococcus aureus, whereas n-hexane extract has shown ZOI 11 ± 0.5 mm against P. aeruginosa. Range of percentage scavenging activity of V. griseus oil extracts from DPPH free radical assay was 34.9-70.7%. For antiviral potential, growth of new castle disease virus (NDV) was effectively inhibited by all five extracts (HA titer = 0-4). The highest antiviral activity against avian influenza virus (H9N2) was observed from methanol, diethyl ether and 1-Butanol oil extracts with HA titers of 2, 2 and 0, respectively. Methanol, diethyl ether, 1-butanol and n-hexane oil extracts produced best hemagglutination assay (HA) titer values (0, 0, 4 and 0) against infectious bronchitis virus (IBV). Ethyl acetate and 1-Butanol extract exhibited good antiviral potential against infectious bursal disease virus (IBDV) with indirect hemagglutination assay (IHA) titers of 8 and 4, respectively. Main classes of identified compounds through gas chromatography were aldehydes, fatty acids, phenols and esters. GC-MS identified 11 bioactive compounds in V. griseus oil extracts. It is summarized that V. griseus oil has strong antioxidant activity and good antimicrobial potential because of its bioactive compounds.

Prediction of methane per unit of dry matter intake in growing and finishing cattle from the ratio of dietary concentrations of starch to neutral detergent fiber alone or in combination with dietary concentration of ether extract.

Previous research demonstrated that a fixed value of 0.2433 (SE = 0.0134) Mcal of CH4/kg of dry matter intake (DMI) could be used to predict CH4 production with accuracy and precision on par with similar equations in the literature. Slope bias was substantially less for the fixed-coefficient equation than noted for the other DMI- or gross energy intake (GEI)-based equations, but mean bias was substantially greater, presumably reflecting the failure of the fixed-coefficient approach to account for dietary factors that affect CH4 production. In this article, we report on the use of the dietary ratio of concentrations of starch to neutral detergent fiber (NDF) and dietary ether extract (EE) concentration to improve the accuracy and precision of the fixed-coefficient equation. The same development data set used to create the fixed-coefficient equation was used in the present study, which included 134 treatment means from 34 respiration calorimetry studies. Based on stepwise regression with dietary NDF, starch, crude protein, EE, and the starch:NDF ratio as possible dependent variables, the starch:NDF ratio and EE were the only dietary variables selected (P ≤ 0.15). The study-adjusted relationship with the starch:NDF ratio (r2 = 0.673; root mean square error [RMSE] = 0.0327) was: Mcal of CH4/kg of DMI = 0.2883 - 0.03474 × starch:NDF; whereas the relationship with a model that included both starch:NDF ratio and dietary EE (r2 = 0.738; RMSE = 0.0315) was: Mcal of CH4/kg of DMI = 0.3227 - 0.0334 × starch:NDF - 0.00868 × % EE. A previously published independent data set with 129 treatment means from 30 respiration calorimetry studies was used to evaluate these two equations, along with two additional equations in which g/d of CH4 was predicted directly from DMI, starch:NDF ratio, and/or dietary EE. The two Mcal of CH4/kg of DMI equations had superior fit statistics to the previously published 0.2433 Mcal of CH4/kg of DMI equation, with a substantial decrease in mean bias and improved concordance correlation coefficients. Moreover, the Mcal of CH4/kg of DMI equations resulted in improved fit relative to direct prediction of g/d of CH4 from DMI, the starch:NDF ratio, and % EE. Based on these results, further evaluation of the dietary ratio of starch-to-NDF concentrations and EE concentration to predict methane production per unit DMI in beef cattle is warranted.

Accurate and precise equations to predict enteric methane production are an important tool as the beef industry works to mitigate greenhouse gas emissions. We predicted the megacalories of methane per unit of dry matter intake using data from growing and finishing beef and dairy steers and heifers. The predicted value was then multiplied by dry matter intake to estimate methane production. The most important predictor variables were the ratio of dietary starch to neutral detergent fiber concentrations and dietary ether extract concentration. When tested with an independent data set, predicting methane per unit dry matter intake from the ratio of starch to neutral detergent fiber, with or without the addition of dietary ether extract as a predictor variable, yielded better fits to the independent data set than equations in which the daily production of methane was predicted directly from dry matter intake, the ratio of starch to neutral detergent fiber, and/or dietary ether extract. Predictions could potentially be further refined by adjusting the starch component of the ratio for degradability in the rumen (e.g., degree of gelatinization or processing) and the neutral detergent fiber content for the contributions from roughage vs. grains and grain byproducts.