Explore the vast range of titles available.

The use of herbal medicines containing Petasites hybridus extracts has a long history in the treatment of various ailments. The observed effects are primarily due to pharmacologically active compounds such as petasin, isopetasin, and neopetasin. In evidence-based phytotherapy, extracts from leaves and rhizomes are applied for different indications. While leaf extracts are administered to treat allergic rhinitis symptoms, rhizome extracts are utilized among others in the management of gastrointestinal spasms and migraines. The quality and source of plants are critical for producing authorized herbal medicinal products. Although the preparation of P. hybridus leaf extracts from cultivated plant material is already established, the rhizomes used for preparing extracts are still derived from commercial wild collections. However, switching to cultivation is desirable to ensure consistent quality and availability. For regulatory purposes, comparative pharmacological studies are needed to assess the bioactivity of plant material from different sources. Therefore, this study analyzed rhizome extracts from wild harvesting and cultivation for their petasin composition (i.e., isopetasin, neopetasin, petasin) and spasmolytic effects on Ca2+-dependent precontracted guinea pig ileum ex vivo. The results confirm petasins as active compounds of P. hybridus rhizome extracts. Moreover, they demonstrate that the total content of petasins determines the spasmolytic effects, regardless of the individual composition of the different petasins. No significant differences in efficacy were found between cultivated and wild-collected rhizomes, demonstrating that cultivated material is a reliable, consistent, and sustainable alternative for P. hybridus rhizome extract production.

The sugar alcohol erythritol occurs naturally in fruits and fermented foods, is used as a sweetener, and is also endogenously synthesized via the pentose-phosphate pathway and metabolized into erythronate. Untargeted metabolomic studies have associated elevated plasma erythritol and erythronate concentrations with metabolic disorders, while weight loss has been linked to decreased plasma erythritol concentrations. In this trial, two complementary analyses were performed to identify predictors of fasting erythritol and erythronate concentrations across different populations and to assess changes in these metabolites following bariatric surgery-induced weight loss. Fasting plasma samples from 30 lean adolescents, 50 lean adults, and 138 adults with obesity (including 15 who had undergone bariatric surgery) were analyzed to measure erythritol, erythronate, glucose, and insulin concentrations. Across all populations, age but not body mass index (BMI), glucose, or insulin, was a significant predictor of fasting erythritol concentrations. Fasting erythronate concentrations were associated with both age and BMI. Post-surgery, change in BMI but not fasting glucose or insulin was a predictor of changes in fasting erythritol concentrations, while time was the only predictor of changes in fasting erythronate concentrations. Although the metabolic processes regulating the endogenous erythritol and erythronate production remain unclear, our findings suggest that age-related physiological changes may influence fasting concentrations of both erythritol and erythronate.

Cimicifuga racemosa extracts, particularly the ethanolic extract Ze 450, are widely used to alleviate menopausal symptoms, such as hot flushes and excessive sweating. While their clinical efficacy is well established, the effects of these interventions on systemic energy metabolism remain unclear. This pilot study investigated the impact of Ze 450 on body composition, metabolic markers, and voluntary physical activity in non-ovariectomized female Wistar rats. Animals (N = 36) received Ze 450 at either 30 mg/kg or 130 mg/kg body weight, with or without access to voluntary wheel running over four weeks. Neither treatment influenced body weight gain or final body weight, indicating normal growth across all groups. Post-mortem analyses included visceral fat mass, serum cholesterol, and leptin levels. Both Ze 450 and running reduced visceral fat mass, adipocyte size, and circulating leptin levels, suggesting that they share overlapping mechanisms. Serum cholesterol was significantly lowered by running but remained unaffected by Ze 450, while liver weight and alanine aminotransferase activity were unchanged, confirming hepatic safety. Collectively, Ze 450 improved key metabolic parameters related to adiposity and appetite without affecting hepatic integrity, highlighting its potential as a safe, non-hormonal metabolic modulator complementary to physical activity.

Cimicifuga racemosa (CR) extracts contain diverse constituents such as saponins. These saponins, which act as a defense against herbivores and pathogens also show promise in treating human conditions such as heart failure, pain, hypercholesterolemia, cancer, and inflammation. Some of these effects are mediated by activating AMP-dependent protein kinase (AMPK). Therefore, comprehensive screening for activating constituents in a CR extract is highly desirable. Employing machine learning (ML) techniques such as Deep Neural Networks (DNN), Logistic Regression Classification (LRC), and Random Forest Classification (RFC) with molecular fingerprint MACCS descriptors, 95 CR constituents were classified. Calibration involved 50 randomly chosen positive and negative controls. LRC achieved the highest overall test accuracy (90.2%), but DNN and RFC surpassed it in precision, sensitivity, specificity, and ROC AUC. All CR constituents were predicted as activators, except for three non-triterpene compounds. The validity of these classifications was supported by good calibration, with misclassifications ranging from 3% to 17% across the various models. High sensitivity (84.5–87.2%) and specificity (84.1–91.4%) suggest suitability for screening. The results demonstrate the potential of triterpene saponins and aglycones in activating AMP-dependent protein kinase (AMPK), providing the rationale for further clinical exploration of CR extracts in metabolic pathway-related conditions.

Background Membrane lipids have an important function in the brain as they not only provide a physical barrier segregating the inner and outer cellular environments, but are also involved in cell signaling. It has been shown that the lipid composition effects membrane fluidity which affects lateral mobility and activity of membrane-bound receptors. Methods Since changes in cellular membrane properties are considered to play an important role in the development of depression, the effect of St. John’s wort extract Ze 117 on plasma membrane fluidity in peripheral blood mononuclear cells (PBMC) was investigated using fluorescence anisotropy measurements. Changes in fatty acid residues in phospholipids after treatment of cortisol-stressed [1 μM] PBMCs with Ze 117 [10–50 µg/ml] were analyzed by mass spectrometry. Results Cortisol increased membrane fluidity significantly by 3%, co-treatment with Ze 117 [50 µg/ml] counteracted this by 4.6%. The increased membrane rigidity by Ze 117 in cortisol-stressed [1 μM] PBMC can be explained by a reduced average number of double bonds and shortened chain length of fatty acid residues in phospholipids, as shown by lipidomics experiments. Conclusion The increase in membrane rigidity after Ze 117 treatment and therefore the ability to normalize membrane structure points to a new mechanism of antidepressant action of the extract.

Random forest, support vector machine, logistic regression, neural networks and k-nearest neighbor (lazar) algorithms, were applied to a new Salmonella mutagenicity dataset with 8,290 unique chemical structures utilizing MolPrint2D and Chemistry Development Kit (CDK) descriptors. Crossvalidation accuracies of all investigated models ranged from 80 to 85% which is comparable with the interlaboratory variability of the Salmonella mutagenicity assay. Pyrrolizidine alkaloid predictions showed a clear distinction between chemical groups, where otonecines had the highest proportion of positive mutagenicity predictions and monoesters the lowest.

The coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (SARS-CoV-2), has spread worldwide, affecting over 250 million people and resulting in over five million deaths. Antivirals that are effective are still limited. The antiviral activities of the Petasites hybdridus CO2 extract Ze 339 were previously reported. Thus, to assess the anti-SARS-CoV-2 activity of Ze 339 as well as isopetasin and neopetasin as major active compounds, a CPE and plaque reduction assay in Vero E6 cells was used for viral output. Antiviral effects were tested using the original virus (Wuhan) and the Delta variant of SARS-CoV-2. The antiviral drug remdesivir was used as control. Pre-treatment with Ze 339 in SARS-CoV-2-infected Vero E6 cells with either virus variant significantly inhibited virus replication with IC50 values of 0.10 and 0.40 μg/mL, respectively. The IC50 values obtained for isopetasin ranged between 0.37 and 0.88 μM for both virus variants, and that of remdesivir ranged between 1.53 and 2.37 μM. In conclusion, Ze 339 as well as the petasins potently inhibited SARS-CoV-2 replication in vitro of the Wuhan and Delta variants. Since time is of essence in finding effective treatments, clinical studies will have to demonstrate if Ze339 can become a therapeutic option to treat SARS-CoV-2 infections.

Gut hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) play a role as satiation factors. Strategies to enhance satiation peptide secretion could provide a therapeutic approach for obesity. Carbohydrates and lipids have been extensively investigated in relation to peptide release. In contrast, the role of proteins or amino acids is less clear. Our aim was to compare the effects of the amino acids L-tryptophan (L-trp) and L-leucine (L-leu) separately on gastric emptying and gut peptide secretion. The study was conducted as a randomized (balanced), double-blind, parallel-group trial. A total of 10 lean and 10 non-diabetic obese participants were included. Participants received intragastric loads of L-trp (0.52 g and 1.56 g) and L-leu (1.56 g), dissolved in 300 mL tap water; 75 g glucose and 300 mL tap water served as control treatments. Results of the study are: i) L-trp at the higher dose stimulates CCK release (p = 0.0018), and induces a significant retardation in gastric emptying (p = 0.0033); ii) L-trp at the higher dose induced a small increase in GLP-1 secretion (p = 0.0257); iii) neither of the amino acids modulated subjective appetite feelings; and iv) the two amino acids did not alter insulin or glucose concentrations. L-trp is a luminal regulator of CCK release with effects on gastric emptying, an effect that could be mediated by CCK. L-trp's effect on GLP-1 secretion is only minor. At the doses given, the two amino acids did not affect subjective appetite feelings. ClinicalTrials.gov NCT02563847.

IntroductionPrevious studies in humans and rats suggest that erythritol might positively affect vascular function, xylitol decrease visceral fat mass and both substances improve glycaemic control. The objective of this study was to investigate the impact of a 5-week intake of erythritol and xylitol on vascular function, abdominal fat and blood lipids, glucose tolerance, uric acid, hepatic enzymes, creatinine, gastrointestinal tolerance and dietary patterns in humans with obesity.MethodsForty-two participants were randomised to consume either 36 g erythritol, 24 g xylitol, or no substance daily for 5 weeks. Before and after the intervention, arterial stiffness (pulse wave velocity, arteriolar-to-venular diameter ratio), abdominal fat (liver volume, liver fat percentage, visceral and subcutaneous adipose tissue, blood lipids), glucose tolerance (glucose and insulin concentrations), uric acid, hepatic enzymes, creatinine, gastrointestinal tolerance and dietary patterns were assessed. Data were analysed by linear mixed effect model.ResultsThe 5-week intake of erythritol and xylitol showed no statistically significant effect on vascular function. Neither the time nor the treatment effects were significantly different for pulse wave velocity (time effect: p=0.079, Cohen’s D (95% CI) −0.14 (−0.54–0.25); treatment effect: p=0.792, Cohen’s D (95% CI) control versus xylitol: −0.11 (–0.61–0.35), control versus erythritol: 0.05 (0.44–0.54), erythritol versus xylitol: 0.07 (–0.41–0.54)). There was no statistically significant effect on abdominal fat, glucose tolerance, uric acid, hepatic enzymes and creatinine. Gastrointestinal tolerance was good except for a few diarrhoea-related symptoms. Participants of all groups reduced their consumption of sweetened beverages and sweets compared with preintervention.ConclusionsThe 5-week intake of erythritol and xylitol showed no statistically significant effects on vascular function, abdominal fat, or glucose tolerance in people with obesity.Clinical trial registration NCT02821923.

Aim: The objective was to investigate the effect of metamizole on renal function in healthy, salt-depleted volunteers. In addition, the pharmacokinetics of the four major metamizole metabolites were assessed and correlated with the pharmacodynamic effect using urinary excretion of the prostacyclin metabolite 6-keto-prostaglandin F1α. Methods: Fifteen healthy male volunteers were studied in an open-label randomized controlled parallel group study. Eight subjects received oral metamizole 1,000 mg three times daily and seven subjects naproxen 500 mg twice daily for 7 days. All subjects were on a low sodium diet (50 mmol sodium/day) starting 1 week prior to dosing until the end of the study. Glomerular filtration rate was measured using inulin clearance. Urinary excretion of sodium, potassium, creatinine, 6-keto-prostaglandin F1α, and pharmacokinetic parameters of naproxen and metamizole metabolites were assessed after the first and after repeated dosing. Results: In moderately sodium-depleted healthy subjects, single or multiple dose metamizole or naproxen did not significantly affect inulin and creatinine clearance or sodium excretion. Both drugs reduced renal 6-keto-prostaglandin F1α excretion after single and repeated dosing. The effect started 2 h after intake, persisted for the entire dosing period and correlated with the concentration-profile of naproxen and the active metamizole metabolite 4-methylaminoantipyrine (4-MAA). PKPD modelling indicated less potent COX-inhibition by 4-MAA (EC 50 0.69 ± 0.27 µM) compared with naproxen (EC 50 0.034 ± 0.033 µM). Conclusions: Short term treatment with metamizole or naproxen has no significant effect on renal function in moderately sodium depleted healthy subjects. At clinically relevant doses, 4-MAA and naproxen both inhibit COX-mediated renal prostacyclin synthesis.