Short-Term Cocoa Supplementation Influences Microbiota Composition and Serum Markers of Lipid Metabolism in Elite Male Soccer Players.

OBJECTIVES: Dietary strategies to improve arachidonic acid:eicosapentaenoic acid (AA:EPA) ratios are of interest due to potential reductions in inflammation and oxidative stress following exercise. The aim of this study was to investigate the impact of a novel dietary intervention, that is, the ingestion of 30 g of dark chocolate, on blood lipid profiles and gut microbiota composition in elite male soccer players. METHODS: Professional male soccer players were randomly assigned to the experimental group (DC) provided with 30 g of dark chocolate or to the control group (WC), provided with 30 g of white chocolate, for 30 days. Before and after intervention, blood, fecal sample, and anthropometry data were collected. For each outcome, two-way repeated-measure analysis of variance was used to identify differences between baseline and endpoint (Week 4), considering treatment (dark chocolate, white chocolate) as intersubjects' factors. Metagenomic analysis was performed following the general guidelines, which relies on the bioBakery computational environment. RESULTS: DC group showed increased plasma polyphenols (from 154.7 ± 18.6 µg gallic acid equivalents/ml to 185.11 ± 57.6 µg gallic acid equivalents/ml, Δ pre vs. post = +30.41 ± 21.50) and significant improvements in lipid profiles: total cholesterol (Δ -32.47 ± 17.18 mg/dl DC vs. Δ -2.84 ± 6.25 mg/dl WC, Time × Treatment interaction p < .001), triglycerides (Δ -6.32 ± 4.96 mg/dl DC vs. Δ -0.42 ± 6.47 mg/dl WC, Time × Treatment interaction p < .001), low-density lipoprotein (Δ -18.42 ± 17.13 mg/dl vs. Δ -2.05 ± 5.19 mg/dl WC, Time × Treatment interaction p < .001), AA/EPA ratio (Δ -5.26 ± 2.35; -54.1% DC vs. Δ -0.47 ± 0.73, -6.41% WC, Time × Treatment interaction p < .001) compared with WC group. In addition, 4 weeks of intervention showed a significant increase in high-density lipoprotein concentration in DC group (Δ + 3.26 ± 4.49 mg/dl DC vs. Δ -0.79 ± 5.12 mg/dl WC). Microbial communities in the DC group maintained a slightly higher microbial stability over time (exhibiting lower within-subject community dissimilarity). CONCLUSION: Ingesting 30 g of dark chocolate over 4 weeks positively improved AA:EPA ratio and maintained gut microbial stability. Dark chocolate ingestion represents an effective nutritional strategy to improve blood lipid profiles in professional soccer players. What Are the Findings? Ingesting 30 g of dark chocolate for 4 weeks positively influences blood lipid AA: EPA ratio while maintaining gut microbial stability. What This Study Adds? Dietary intake of specific foods such as dark chocolate represents an alternative strategy to support the health and recovery of elite soccer players. What Impact Might This Have on Clinical Practice in the Future? From a clinical and translational perspective, dark chocolate ingestion positively modulates favorable blood lipid profiles and polyunsaturated fatty acid metabolism while maintaining gut microbial stability. Dark chocolate ingestion may be considered as an effective nutritional strategy in elite sport environments during periods of high-intensity training and congested competitions. Further research is required to determine functional outcomes associated with the observed improvements in blood lipid profiles.

Relationship between the root processing method and quality of herbal medicine of Rauvolfia serpentina cultivated in Japan.

Rauvolfia serpentina roots are used as herbal medicine for snake and insect bites, fever, malaria, abdominal pain, hypertension, and dysentery in Southeast Asian countries. This study evaluates the content of reserpine, ajmaline, and ajmalicine in R. serpentina roots obtained with an efficient root processing method. The plants were cultivated in Tanegashima Island in southern part of Japan, where NIBIOHN's experimental farm station is located. We examined both the type of cork layer removal method (manual work, drum mixer washing, and high-pressure washing) and dried roots. We found that the resulting active ingredient contents were not significantly different between manual work and 30 min of drum mixer washing, and high-pressure washing. The washing in a drum mixer for 30 min could be an efficient root processing method. The amount of each active ingredient was compared in each root part (large-, middle-, and small-diameter roots), and there were no significant difference in their contents. In conclusion, R. serpentina roots having a diameter ≥ 0.5 cm contain a similar amount of active ingredients, suggesting that the quality of the crude drug does not vary in the root part. Thus, our study provides significant insights into the use of R. serpentina roots for herbal medicine applications as well as constituents of active ingredients.

Cannabis sativa essential oils orally administered to CD1 mice: Tissue distribution of main constituents.

The essential oil (EO) obtained from hemp (Cannabis sativa L.) biomass is rich of bioactive constituents and its oral administration can be valuable. In this paper two different hemp EOs were orally administered to CD1 mice. One EO, obtained from the fresh plant material, resulted rich in monoterpenes (monoterpene rich oil, MRO) and the other, obtained from the dried biomass, contained mainly sesquiterpenes and CBD (sesquiterpene rich oil, SRO). The blood levels of the most abundant constituents were evaluated in the animals 30 and 90 min after oral administration of hemp EOs. Furthermore, compounds were also measured in brain, liver, kidney, spleen, and cecum content to evaluate their tissue distribution at the same times. Results showed the easy absorption and the ability of the major hemp EOs constituents to reach brain, liver, and kidney. Oral administration of MRO resulted in blood levels of monoterpenes in the range 45-115 ng/g at 30 min and significant tissue distribution with the detection of monoterpenes in brain, liver, and kidney. Oral administration of SRO resulted in blood levels, at 30 min, in the range 70-80 ng/g of sesquiterpenes and 139 ng/g of CBD. The compounds are still detectable in blood and brain 90 min after oral administration and significant concentrations of terpenoids are observed in liver and kidney. MRO and SRO can be considered as valuable sources of these bioactive compounds and further investigations are needed to evaluate the potential uses of hemp EO as constituent of innovative drug formulations.

Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice.

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin-the most concentrated flavonoid in HK-as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16-CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16-CDK6 interaction.

Bioactive alkaloids from Nepalese Corydalis chaerophylla D.C. acting on the regulation of PCSK9 and LDL-R in vitro.

Four new alkaloids Chaeronepaline-A (1), Chaeronepaline-B (2), Chaeronepaline-C (3), and Chaeronepaline-D (4) were isolated from Corydalis chaerophylla D.C. collected from Nepal and their structures were elucidated by spectroscopic data, 1D, 2D NMR and mass spectrometry. The structures were established as 3,12- Dimethoxy-5,6-dihydroisoquinolino [2,1-b] isoquinolin- 7- ium- 2, 9- diol (1), 7-methyl-5, 6, 7, 8-tetrahydroisoquinoline- 2, 3- methylenedioxy- (8-> 9)- 10, 12- methylenedioxy- benzoic-16-acid (2), 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline (3) and 7- methyl-5, 6, 7, 8- tetrahydro- 8H-spiro-9,14-dihydroxy-11,12-methylenedioxy-indane-isoquinoline-N-oxide (4). The new alkaloids were tested in human hepatoma cell line to assess their ability to modulate the expression of low-density lipoprotein receptor (LDL-R), of proprotein convertase subtilisin/kexin 9 (PCSK9) and to affect cellular cholesterol biosynthesis with the aim to evaluate their potential hypocholesterolemic effect. Results indicated that compounds 2 and 3 upregulate the LDLR, and inhibited the cholesterol biosynthesis with compound 2, which also reduced the secretion of PCSK9 by Huh7 cells. These in vitro data indicated a potential hypocholesterolemic effect of compound 2 that requires further in vivo validation.

Exploring Chemical Composition, Antioxidant, Enzyme Inhibitory and Cytotoxic Properties of Glaucium acutidentatum Hausskn. & Bornm. from Turkey Flora: A Novel Source of Bioactive Agents to Design Functional Applications.

The present study was performed to determine the chemical constituents, cytotoxicity, antioxidant and enzyme inhibition activities of the aerial parts of Glaucium acutidentatum Hausskn. and Bornm. (family Papaveraceae). Methanolic and aqueous extracts were prepared by maceration, homogenizer-assisted extraction (HAE) and infusion. Results showed that the highest total phenolic and flavonoids contents were obtained from the methanol extracts obtained by HAE (53.22 ± 0.10 mg GAE/g) and maceration (30.28 ± 0.51 mg RE/g), respectively. The aporphine, beznyltetrahydroisoquinoline, and protopine types of Glaucium alkaloids have been tentatively identified. Among them, glaucine was identified in all extracts. Flavonoids, phenolic acids, coumarins, organic acids and fatty acids were also detected. Methanolic extract obtained using the HAE method displayed the highest anti-DPPH (41.42 ± 0.62 mg TE/g), total antioxidant (1.20 ± 0.17 mmol TE/g), Cu2+ (113.55 ± 6.44 mg TE/g), and Fe3+ (74.52 ± 4.74 mg TE/g) reducing properties. The aqueous extracts obtained by infusion and HAE methods exerted the best anti-ABTS (103.59 ± 1.49 mg TE/g) and chelating (19.81 ± 0.05 mg EDTAE/g) activities, respectively. Methanolic extract from HAE recorded the highest acetylcholinesterase (2.55 ± 0.10 mg GALAE/g) and α-amylase (0.51 ± 0.02 mmol ACAE/g) inhibition activities, while that obtained by maceration showed the best butyrylcholinesterase (3.76 ± 0.31 mg GALAE/g) inhibition activity. Both extracts revealed the best tyrosinase inhibitory activity (25.15 ± 1.00 and 26.79 ± 2.36 mg KAE/g, p ≥ 0.05). G. acutidentatum maceration-derived aqueous extract showed selective anticancer activity against cells originating from human hypopharyngeal carcinoma. In conclusion, these findings indicated that G. acutidentatum is a promising source of alkaloids and phenolic compounds for variable pharmaceutical formulations.

Chemical Characterization, Free Radical Scavenging, and Cellular Antioxidant Properties of the Egadi Island Endemic Brassica macrocarpa Guss Leaf Extract.

The genus Brassica is an important source of food in the Mediterranean diet with documented nutritional and medicinal properties. However, few studies have investigated the phytochemical composition and the biological activity of wild Sicilian taxa. Thus, we aimed to study the chemical profile and the antioxidant potential, in vitro and in LPS-stimulated RAW 264.7 cells, of a methanolic extract of leaves of wild Brassica macrocarpa Guss (B. macrocarpa) (Egadi Islands; Sicily-Italy). B. macrocarpa methanolic extract showed a large amount of glucosinolates and different phenolic compounds. It exhibited antioxidant activity in the DPPH assay and in LPS-stimulated RAW 264.7 cells, being able to reduce NO and ROS levels and NOS2 mRNA expression. Our study demonstrated that Sicilian B. macrocarpa methanolic extract, in LPS-stimulated macrophages, efficiently counteracts oxidative stress and displays radical scavenging activity. Future studies are required to identify the contribution of the single phytocomponents, to characterize the action mechanism, and to reveal possible applications in human health.

Ultrasound-assisted extraction of bioactive compounds from goji berries: Optimization, bioactivity, and intestinal permeability assessment.

Lycium barbarum L. berries have a remarkable chemical composition and extensive biological activities, being a valuable component of health and nutraceutical practices. Nevertheless, a deep insight on the intestinal permeation of the pro-healthy bioactive compounds is urgently needed to predict the real effects on human body. This study attempted, for the first time, to optimize the Ultrasound-Assisted Extraction (UAE) of goji berries using a Response Surface Methodology approach and establish the intestinal permeation of the principal pro-healthy compounds. The optimal extraction conditions were a solid:liquid ratio of 8.75 % for 56.21 min, using an intensity of 59.05 W/m2. The optimal extract displayed a remarkable antioxidant capacity, with LC/DAD-ESI-MS analysis unveiled a diverse phytochemical profile, encompassing different compounds (e.g. glu-lycibarbarspermidine F, 2-glu-kukoamine, rutin, 3,5-dicaffeoylquinic acid). The intestinal co-culture model demonstrated that glu-lycibarbarspermidine F (isomer 2) (73.70 %), 3,5-dicaffeoylquinic acid (52.66 %), and isorhamnetin-3-O-rutinoside (49.31 %) traversed the intestinal cell layer, exerting beneficial health-promoting effects.

Combining chemical profiles and biological abilities of different extracts from Tanacetum nitens ( Boiss. & Noë) Grierson using network pharmacology.

Tanacetum nitens ( Boiss. & Noë)  Grierson is an aromatic perennial herb used in Turkish traditional medicine to treat headache, fever, and skin diseases. This study aimed to investigate the chemical composition, antioxidant, enzyme inhibition, and cytotoxic properties of T. nitens aerial parts. Organic solvent extracts were prepared by sequential maceration in hexane, dichloromethane, ethyl acetate, and methanol while aqueous extracts were obtained by maceration or infusion. Nuclear magnetic resonance (NMR) and LC-DAD-MS analysis allowed the identification and quantification of different phytoconstituents including parthenolide, tanacetol B, tatridin B, quinic acid derivatives, ß-sitosterol, and glycoside derivatives of quercetin and luteolin. The type and amount of these phytochemicals recovered by each solvent were variable and significant enough to impact the biological activities of the plant. Methanolic and aqueous extracts displayed the highest scavenging and ions-reducing properties while the dichloromethane and ethyl acetate extracts exerted the best total antioxidant activity and metal chelating power. Results of enzyme inhibition activity showed that the hexane, ethyl acetate, and dichloromethane extracts had comparable anti-acetylcholinesterase activity and the latter extract revealed the highest anti-butyrylcholinesterase activity. The best α-amylase and α-glucosidase inhibition activities were obtained from the hexane extract. The dichloromethane and ethyl acetate extracts exhibited the highest cytotoxic effect against the prostate carcinoma DU-145 cells. In conclusion, these findings indicated that T. nitens can be a promising source of biomolecules with potential therapeutic applications.

Identification of hydroxyquinazoline alkaloids from Justicia adhatoda L. leaves, a traditional natural remedy with NF-κB and AP-1-mediated anti-inflammatory properties and antioxidant activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Justicia adhatoda L. is used as traditional medicine in Nepal to treat cough, asthma, and inflammatory disorders, and is indicated as "Asuro". Leaves are used worldwide as herbal medicine due to cardiotonic, expectorant, anti-asthmatic, and bronchodilatory properties. The aim of this work was to study the phytochemical composition of leaves of Nepalese J. adhatoda and assess their anti-inflammatory and antioxidant properties in vitro. MATERIALS AND METHODS: Secondary metabolites were extracted from dried leaves using methanol (JAME: J. adhatoda methanol extract). They were analysed by means of liquid chromatography coupled with multiple-stage mass spectrometry (LC-MSn). Anti-inflammatory potential was determined by the NF-κB and AP-1 inhibition assay, and DPPH, ABTS, and ß-carotene bleaching assays were performed to assess its antioxidant properties. RESULTS: JAME is a rich source of secondary metabolites, especially quinazoline alkaloids such as vasicine, vasicinone, vasicoline, and adhatodine. 7-Hydroxy derivatives of peganidine, vasicolinone, and adhatodine were also identified by means of MSn data and are here reported in J. adhatoda for the first time. JAME inhibited NF-κB and AP-1 expression in THP-1 cells to a greater extent than the positive control prednisolone. A moderate radical-quenching property was observed in DPPH and ABTS assays, but the anti-carotene bleaching activity was significantly higher than the reference BHT. CONCLUSIONS: To the best of our knowledge, this is the first insight into the phytochemical composition of Asuro leaves from Nepal and their bioactivity. Our results will contribute to the valorisation of this medicinal species still widely used in the traditional and complementary medicine.

Analyzing the Chemical Constituents and In Vitro Biological Effects of Extracts Artemisia absinthium L. Extracts Obtained Using Different Methodologies and Solvents.

The present study aimed to investigate the chemical constituents of different extracts from aerial parts of A. absinthium and to evaluate their antioxidant and enzyme inhibition activity. Extracts were prepared by maceration, infusion or Soxhlet techniques. Results showed that the highest total phenolic and flavonoids contents was recorded respectively from the hexane extract prepared by maceration and ethyl acetate extract obtained by Soxhlet method. The characteristic compounds of Artemisia species artemetin, casticin, sesartemin and yangambin in addition to coumarins were identified in all extracts. Aqueous extract obtained by infusion exerted the highest radical scavenging and ions reducing properties while that prepared by maceration displayed the highest chelating power. Methanol extracts obtained by the two methods of extraction exerted the highest anti-Tyr activity while that obtained by maceration showed the best α-glucosidase inhibition activity. These findings indicated that A. absinthium is a rich source of bioactive molecules with possible therapeutic applications.

Gene Silencing of Angiopoietin-like 3 (ANGPTL3) Induced De Novo Lipogenesis and Lipid Accumulation in Huh7 Cell Line.

Angiopoietin-like 3 (ANGPTL3) is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL). Vupanorsen, an ANGPTL3 directed antisense oligonucleotide, showed an unexpected increase in liver fat content in humans. Here, we investigated the molecular mechanism linking ANGPTL3 silencing to hepatocyte fat accumulation. Human hepatocarcinoma Huh7 cells were treated with small interfering RNA (siRNA) directed to ANGPTL3, human recombinant ANGPTL3 (recANGPTL3), or their combination. Using Western blot, Oil Red-O, biochemical assays, and ELISA, we analyzed the expression of genes and proteins involved in lipid metabolism. Oil Red-O staining demonstrated that lipid content increased after 48 h of ANGPTL3 silencing (5.89 ± 0.33 fold), incubation with recANGPTL3 (4.08 ± 0.35 fold), or their combination (8.56 ± 0.18 fold), compared to untreated cells. This effect was also confirmed in Huh7-LX2 spheroids. A total of 48 h of ANGPTL3 silencing induced the expression of genes involved in the de novo lipogenesis, such as fatty acid synthase, stearoyl-CoA desaturase, ATP citrate lyase, and Acetyl-Coenzyme A Carboxylase 1 together with the proprotein convertase subtilisin/kexin 9 (PCSK9). Time-course experiments revealed that 6 h post transfection with ANGPTL3-siRNA, the cholesterol esterification by Acyl-coenzyme A cholesterol acyltransferase (ACAT) was reduced, as well as total cholesterol content, while an opposite effect was observed at 48 h. Under the same experimental conditions, no differences in secreted apoB and PCSK9 were observed. Since PCSK9 was altered by the treatment, we tested a possible co-regulation between the two genes. The effect of ANGPTL3-siRNA on the expression of genes involved in the de novo lipogenesis was not counteracted by gene silencing of PCSK9. In conclusion, our in vitro study suggests that ANGPTL3 silencing determines lipid accumulation in Huh7 cells by inducing the de novo lipogenesis independently from PCSK9.

Dibenzocyclooctadiene Lignans from Schisandra chinensis with Anti-Inflammatory Effects.

Schisandra chinensis (Schisandraceae) is a medicinal plant widely used in traditional Chinese medicine. Under the name Wu Wei Zi, it is used to treat many diseases, especially as a stimulant, adaptogen, and hepatoprotective. Dibenzocyclooctadiene lignans are the main compounds responsible for the effect of S. chinensis. As a part of ongoing studies to identify and evaluate anti-inflammatory natural compounds, we isolated a series of dibenzocyclooctadiene lignans and evaluated their biological activity. Furthermore, we isolated new sesquiterpene 7,7-dimethyl-11-methylidenespiro[5.5]undec-2-ene-3-carboxylic acid. Selected dibenzocyclooctadiene lignans were tested to assess their anti-inflammatory potential in LPS-stimulated monocytes by monitoring their anti-NF-κB activity, antioxidant activity in CAA assay, and their effect on gap junction intercellular communication in WB-ras cells. Some S. chinensis lignans showed antioxidant activity in CAA mode and affected the gap junction intercellular communication. The anti-inflammatory activity was proven for (-)-gomisin N, (+)-γ-schisandrin, rubrisandrin A, and (-)-gomisin J.

Advances in sample preparation methods for pesticide residue analysis in medicinal plants: A focus on Nepal.

Medicinal plant safety is a rising challenge worldwide due to the continued overuse of pesticides to their maximum residue limits. Due to the high demand for medicinal plants, their production is being increased and sometimes protected by pesticide use. The analysis of these residues requires robust analytical methods to ensure the safety and quality of medicinal plants. Developing effective sample preparation for detecting pesticides is challenging, due to their diverse natures, classes, and physico-chemical characteristics. Hence, existing techniques and strategies are needed to improve the reliability of the results. The review discusses the current state of sample preparation techniques, analytical methods, and instrumental technologies employed in pesticide residue analysis in medicinal plants. It highlights the challenges, limitations, and advancements in the field, providing insights into the analytical strategies used to detect and quantify pesticide residues. Reliable, accessible, affordable, and high-resolution analytical procedures are essential to ensure that pesticide levels in medicinal plants are effectively regulated. By understanding the complexities of pesticide residue analysis in medicinal plants, this review article aims to support the conservation of medicinal plant resources, promote public health, and contribute to the development of sustainable strategies for ensuring the safety and quality of medicinal plants in Nepal. The findings of this review will benefit researchers, policymakers, and stakeholders involved in the conservation of medicinal plant resources and the promotion of public health.

A Bronze Age lip-paint from southeastern Iran.

A small chlorite vial, discovered among numerous artifacts looted and recovered in the Jiroft region of Kerman province, southeastern Iran, contains a deep red cosmetic preparation that is likely a lip-coloring paint or paste. Through analytical research involving XRD (X-ray diffraction), SEM-EDS (scanning electron microscopy-energy-dispersive spectroscopy), and HPLC-MS (high-performance liquid chromatography-mass spectrometry) analyses, the mineral components of the reddish substance were identified as hematite, darkened with manganite and braunite, and traces of galena and anglesite, mixed with vegetal waxes and other organic substances. The mixture, thus observed, bears a striking resemblance to the recipes of contemporary lipsticks. We also report the first radiocarbon date ever obtained from a Bronze age cosmetic in the ancient Near East: results place the pigment in the early 2nd millennium BCE, a date compatible with several mentions of the powerful eastern-iranian civilization of Marhasi in coeval cuneiform texts of Mesopotamia, as well as with its currently emerging archaeological picture.

The kynurenine pathway in treatment-resistant schizophrenia at the crossroads between pathophysiology and pharmacotherapy.

Two cardinal elements in the complex and multifaceted pathophysiology of schizophrenia (SCZ) are neuroinflammation and dysregulation of glutamatergic neurotransmission, with the latter being especially involved in treatment-resistant schizophrenia (TRS). Interestingly, the Kynurenine (KYN) pathway (KP) is at the crossroad between them, constituting a potential causal link and a therapeutic target. Although there is preclinical and clinical evidence indicating a dysregulation of KP associated with the clinical phenotype of SCZ, clinical studies investigating the possible relationship between changes in biomarkers of the KP and response to pharmacotherapy are still limited. Therefore, we have studied possible differences in the circulating levels of biomarkers of the metabolism of tryptophan along the KP in 43 responders to first-line treatments (FLR) and 32 TRS patients treated with clozapine, and their possible associations with psychopathology in the two subgroups. Plasma levels of KYN were significantly higher in TRS patients than in FLR patients, indicating a greater activation of KP. Furthermore, the levels of quinolinic (NMDA receptor agonist) and kynurenic acid (NMDA negative allosteric modulator) showed a negative and a positive correlation with several dimensions and the overall symptomatology in the whole sample and in FLR, but not in TRS, suggesting a putative modulating effect of clozapine elicited through the NMDA receptors. Despite the cross-sectional design of the study that prevents us from demonstrating causation, these findings show a significant relationship among circulating KP biomarkers, psychopathology, and response to pharmacotherapy in SCZ. Therefore, plasma KP biomarkers should be further investigated for developing personalized medicine approaches in SCZ.

Phytochemical analysis of Clinopodium candidissimum (Munby) Kuntze growing in Algeria by an integrated HS-SPME-GC-MS, NMR and HPLC-DAD-MSn approach: valorisation of an endemic natural source of bioactive compounds.

Clinopodium candidissimum (Munby) Kuntze (Lamiaceae) is used in traditional medicine and as a food condiment in Algeria, where it is known as Zaater cheleuh and Nabta elbida. Here, we report the comprehensive characterisation of non-volatile polar constituents extracted from C. candidissimum aerial parts (a mixture of inflorescences, stems and leaves), and their aroma profile. Qualitative 1H-NMR and quali-quantitative HPLC-MSn analyses of fractions obtained with solvents at different polarity revealed the presence of aglyconic and glycosylated flavonoids (3.1%), phenylpropanoids (3.6%), gallic acid derivatives (0.76%), and triterpenoids (0.62%), among the others. On the other hand, HS-SPME-GC-MS allowed to identify 38 volatile constituents, among which the oxygenated monoterpenes pulegone (44.8%), piperitenone (6.6%), isopulegone (5.8%) and neo-menthol (3.8%), and the sesquiterpene hydrocarbons germacrene D (16.2%) and bicyclogermacrene (3.0%) were the most abundant. Overall, results indicate that C. candidissimum represents an endemic natural source of antioxidants and bioactive compounds, and they will be useful for further studies on this species.

Lipidomic Profile of Human Sperm Membrane Identifies a Clustering of Lipids Associated with Semen Quality and Function.

Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29). In parallel, we evaluated their serum lipid levels. Twenty-one lipids were identified by their mass/charge ratio and post-source decay spectra. Sulfogalactosylglycerolipid (SGG, seminolipid) was the most abundant lipid component in the membranes. In addition, we observed a significant proportion of PUFAs. Important differences have emerged between the fertile and infertile groups, leading to the identification of a lipid cluster that was associated with semen parameters. Among these, cholesterol sulfate, SGG, and PUFAs represented the most important predictors of semen quality. No association was found between the serum and sperm lipids. Dietary PUFAs and SGG have acknowledged antioxidant functions and could, therefore, represent sensitive markers of sperm quality and testicular function. Altogether, these results underline the important role of sperm membrane lipids, which act independently of serum lipids levels and may rather represent an independent marker of reproductive function.