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Cannabidiol (CBD) is a non-psychoactive phyto-cannabinoid derived from the plant. CBD exhibits various interactions at receptor sites, prompting the research of its potential anti-inflammatory, immunomodulatory, psychological, and pain-relieving effects. This study aimed to investigate the physiological, biochemical, and psychometric effects of a brand-specific, hemp-derived CBD product in healthy adults over a 12-week observation period. 54 healthy males and females (age = 25 ± 7y; BMI = 24.82 ± 3.25 kg/m ) recruited from a large Southeastern University completed the study. Participants arrived at the laboratory after > 8 h of fasting, and > 48 h without alcohol consumption and vigorous exercise. Following baseline measurements (height, weight, blood pressure, electrocardiogram (ECG), and blood work), participants were stratified by sex and randomized to either CBD or placebo groups. Products were administered double-blinded, with both given in liquid form containing medium-chain triglyceride oil, while the CBD product specifically contained 50 mg/mL of CBD. Participants were instructed to consume 1 mL of their product twice daily and were given enough product to last until their next laboratory visit. Data were collected at baseline and on days 30 ± 3, 60 ± 3, and 90 ± 3. Blood was drawn for analysis of immune and inflammatory biomarkers. Chronic pain among participants was calculated using urine samples according to the foundational pain index (FPI). Self-reported psychometric questionnaires were utilized (Cohen's Perceived Stress Scale, Pittsburgh Sleep Quality Index, Profile of Mood States,10-item Likert scale for perceived pain) to assess stress, sleep quality, mood state, and body discomfort. To determine overall wellbeing, participants completed a daily survey indicating if they missed work or school due to illness. Change from baseline was calculated for each measure, and mixed effects models were used to determine differences between groups over time while adjusting for baseline values (α = 0.05). Data are presented as mean ± standard deviation. There were no Group-by-Time interactions or Group or Time main effects for immune or inflammatory biomarkers (  > 0.05). Analyses revealed no Group-by-Time interactions or main effects observed for perceived stress, sleep quality, overall mood disturbance, and all the profile of mood state subscales (  > 0.05), except \"vigor-activity.\" A Time main effect was found for the sub-score for \"vigor-activity\" (  = 0.007; Pre CBD = 19.5 ± 5.2, Post CBD = 17.3 ± 5.3; Pre PL = 19.0 ± 5.7, Post PL = 17.9 ± 7.1), which decreased from Visit 3 to Visit 4 (  = 0.025) and from Visit 3 to Visit 5 (  = 0.014). There was a Group main effect for FPI (  = 0.028; Pre CBD = 11.9 ± 14.4, Post CBD = 8.8 ± 10.9; Pre PL = 9.0 ± 14.2, Post PL = 12.9 ± 11.5), indicating that the placebo group had greater increases in pain over the intervention compared to the CBD group. No significant differences were found between groups in the incidence and prevalence of \"colds or flus\" (  > 0.05). CBD was safe and well tolerated in healthy adults. These findings show pain was lower in the CBD group, suggesting a potentially positive effect for consumption of CBD. \"Vigor-activity\" decreased across the intervention, which may be a confounding effect of the academic semester. While the dosage chosen was safe, more research may be warranted using higher doses as these may be needed to observe further therapeutic effects in healthy populations.

Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6), in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171) were randomized (1:1) to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI) score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs) in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in) and/or short duration of treatment may have masked a potential beneficial effect on sleep quality.

Intermittent fasting improves metabolic and cardiac health. However, increased hunger towards the end of the fasting period may affect compliance and limit its application. Our aim was to determine the effect of anorexigenic agent co-therapy on subjective ratings of appetite during the 16–24 h period of a day-long water-only intermittent fast. Thirty adult men were recruited and required to fast for 24 h from 18:00 h to 18:00 h on the same day of the week for three subsequent weeks. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 100 mg) of a bitter hops-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast. From 18–24 h of the 24 h fast, both the HD and LD treatment groups exhibited a statistically significant (p < 0.05) > 10% reduction in hunger. Additionally, the expected lunchtime increase in hunger that was present in the placebo group (12:00 h) was absent in both the HD and LD groups. These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during intermittent fasting, and show that bitter compounds may regulate appetite independently of meal timing.

Background Hops are the main components of beer that provide flavor and bitterness. Iso-α-acids, the bitter components of beer, have been reported to reduce body fat in humans, but the bitterness induced by effective doses of iso-α-acids precludes their acceptance as a nutrient. The matured hop bitter acids (MHBA) of oxidized hops appear to have a more pleasant bitterness compared to the sharper bitterness of iso-α-acids. While there has been little information concerning the identity of the MHBA compounds and their physiological effects, MHBA was recently found to be primarily composed of oxides derived from α-acids, and structurally similar to iso-α-acids. Here, we investigated the effects of matured hop extract (MHE) containing MHBA on reducing abdominal body fat in healthy subjects with a body mass index (BMI) of 25 to below 30 kg/m 2 , classified as “obese level 1” in Japan or as “overweight” by the WHO. Trial design A randomized, double-blind, placebo-controlled parallel group study. Methods Two hundred subjects (male and female aged 20 to below 65 years with a BMI of 25 or more and less than 30 kg/m 2 ) were randomly assigned to two groups. During a 12-week ingestion period, the subjects in each group ingested daily 350 mL of test-beverage, either containing MHE (with 35 mg MHBA), i.e. the namely active beverage, or a placebo beverage without MHE. The primary endpoint was reduction of the abdominal fat area as determined by CT scanning after continual ingestion of MHE for 12 weeks. Results Compared to the placebo group, a significant reduction was observed in the visceral fat area after 8 and 12 w, and in the total fat area after 12 w in the active group. There was also a concomitant decrease in body fat ratio in the active group compared to the placebo group. No adverse events related to the test beverages or clinically relevant abnormal changes in the circulatory, blood and urine parameters were observed in either group. Conclusions The present study suggests that continual ingestion of MHE safely reduces body fat, particularly the abdominal visceral fat of healthy overweight subjects. Trial registration UMIN-CTR UMIN000014185

To assess the efficacy and safety of NSF-3, a polyherbal sedative-hypnotic (containing standardized extracts of Valeriana officinalis, Passiflora incarnate and Humulus lupulus), in comparison to zolpidem in primary insomnia. The present study was designed as a parallel group, double- blind, randomized, controlled trial and registered with Clinical Trials Registry-India (CTRI/2011/12/002197). Patients diagnosed with primary insomnia with a perceived total sleep time of <6 hours per night and insomnia severity index >7 were included. They were treated with either NSF-3 (one tablet) or zolpidem (one 10 mg tablet) at bedtime for two weeks. Total sleep time, sleep latency and number of awakenings per night were assessed using a sleep diary. Quality of life and daytime sleepiness were evaluated by insomnia severity index and Epworth sleepiness score respectively. Vital signs, routine blood counts, liver and renal function tests, and treatment emergent adverse events were recorded for safety assessment. A total of 91 subjects were recruited, of which 39 in each group completed the study. There was significant improvement in total sleep time, sleep latency, number of nightly awakenings and insomnia severity index scores in both groups. However, no statistically significant difference was observed between the groups. Epworth sleepiness scores did not change significantly over the study period. Although 12 treatment emergent adverse events were reported with NSF-3 and 16 with zolpidem (commonest was drowsiness in both), most were mild and no serious adverse events were encountered. NSF-3 is a safe and effective short-term alternative to zolpidem for primary insomnia. It remains to be explored whether the benefits are sustained and whether there is dependence liability with this formulation upon long term use.

Hop ( Humulus lupulus L.) is an emblematic industrial crop in the French North East region that developed at the same time as the brewing activity. Presently, this sector, especially microbreweries, are interested in endemic wild hops, which give beer production a local signature. In this study, we investigated the genetic and metabolic diversity of thirty-six wild hops sampled in various ecological environments. These wild accessions were propagated aeroponically and cultivated under uniform conditions (the same soil and the same environmental factors). Our phytochemical approach based on UHPLC-ESI-MS/MS analysis led to the identification of three metabolic clusters based on leaf content and characterized by variations in the contents of twelve specialized metabolites that were identified (including xanthohumol, bitter acids, and their oxidized derivatives). Furthermore, molecular characterization was carried out using sixteen EST-SSR microsatellites, allowing a genetic affiliation of our wild hops with hop varieties cultivated worldwide and wild hops genotyped to date using this method. Genetic proximity was observed for both European wild and hop varieties, especially for Strisselspalt, the historical variety of our region. Finally, our findings collectively assessed the impact of the hop genotype on the chemical phenotype through multivariate regression tree (MRT) analysis. Our results highlighted the ’WRKY 224’ allele as a key discriminator between high- and low-metabolite producers. Moreover, the model based on genetic information explained 40% of the variance in the metabolic data. However, despite this strong association, the model lacked predictive power, suggesting that its applicability may be confined to the datasets analyzed.

Xanthohumol (Xn), a prenylated chalcone found in Hop (Humulus lupulus L.), has been shown to have potent anti-aging, diabetes, inflammation, microbial infection, and cancer properties. Unfortunately, this molecule has undesirable characteristics such as inadequate intake, low aqueous solubility, and a short half-life. To address these drawbacks, researchers have made numerous attempts to improve its absorption, solubility, and bioavailability. Polymeric drug delivery systems (PDDSs) have experienced significant development over the last two decades. Polymeric drug delivery is defined as a formulation or device that allows the introduction of a therapeutic substance into the body. Biodegradable and bioreducible polymers are the ideal choice for a variety of new DDSs. Xn formulations based on biodegradable polymers and naturally derived compounds could solve some of the major drawbacks of Xn-based drug delivery. In this regard, the primary concern of this study is on presenting innovative formulations for Xn delivery, such as nanoparticles (NPs), nanomicelles, nanoliposomes, solid lipid nanoparticles (SLNs), and others, as well as the received in vitro and in vivo data. Furthermore, this work describes the chemistry and broad biological activity of Xn, which is particularly useful in modern drug technology as well as the cosmetics industry. It is also important to point out that the safety of using Xn, and its biotransformation, pharmacokinetics, and clinical applications, have been thoroughly explained in this review.

Accelerated solvent extraction (ASE) is widely used for recovering bioactive compounds from hops; however, the extent to which global antioxidant assays reflect changes in molecular composition remains unclear. This study evaluated the relationship between global antioxidant parameters and targeted profiling of prenylated flavonoids in hop extracts obtained under different ASE conditions. Total antioxidant capacity (TAC), total phenolic content (TPC), and concentrations of xanthohumol, isoxanthohumol, and 8-prenylnaringenin were determined in extracts prepared using different solvents, extraction temperatures, and homogenization approaches. Global antioxidant parameters responded consistently to technological factors and exhibited a strong mutual correlation. In contrast, their correlations with individual prenylated flavonoids were moderate, indicating that global assays capture only part of the variability associated with specific bioactive compounds. Extraction temperature emerged as a key modulating factor, inducing compound-specific and partly non-linear responses that were not fully reflected by global antioxidant methods. Principal component analysis confirmed a shared chemical trend linking global and targeted parameters while separating extraction temperature as an independent technological driver. Overall, global antioxidant assays provide a robust but simplified assessment of hop extract quality. Their combination with targeted chromatographic analysis enables more accurate interpretation of extraction behavior and supports informed process optimization aimed at preserving and recovering bioactive compounds.

Prenylated chalcones and flavonoids gained increasing attention not only in nutrition but also in cancer prevention because of their biological and molecular activities in humans, which have been extensively investigated in vitro or in preclinical studies. These naturally occurring compounds exhibit antioxidant effects, modulate metabolism of carcinogens by inhibition of distinct phase 1 metabolic enzymes and activation of phase 2 detoxifying enzymes, and display antiinflammatory properties. In particular, their potential to prevent proliferation of tumor cells is noteworthy. Some representatives of this subclass of secondary plant compounds exert pronounced anti–tumor-initiating capacities and directly inhibit growth of cancer cells, whereas their toxic effects on healthy tissues are remarkably low. These promising pharmacologic characteristics are countered by low ingestion, low bioavailability, and little knowledge of their metabolism. This review focuses on the great potential of these plant- and nutrient-derived compounds for cancer prevention and therapy. Provided here is a comprehensive summary of the current knowledge and inherent modes of action, focusing on the prenylated chalcones xanthohumol, desmethylxanthohumol, and xanthogalenol, as well as the prenylated flavonoids isoxanthohumol, 6-prenylnaringenin, 8-prenylnaringenin, 6-geranylnaringenin, 8-geranylnaringenin, and pomiferin. •Foods like hops are important sources of prenylated chalcones and flavonoids.•Prenylated chalcones and flavonoids exhibit promising health-promoting properties in preclinical studies.•Prenylated derivatives are interesting for both prevention and treatment of cancer.

In recent years, there has been a surge in the production of kombucha—a functional beverage obtained via microbial fermentation of tea. However, fresh, unpasteurized kombucha is sensitive to quality deterioration as a result of, among other factors, oxidation. The addition of hops seems to be promising, due to their antioxidative properties, which may improve the stability of kombucha. However, aiming at retaining the highest antioxidative properties of kombucha, it remains unclear at which stage of the production process hops should be added. The study investigated the effect of hop supplementation during kombucha production on the basic physicochemical, antioxidative, and sensory properties of kombucha. Cascade hops in the concentrations 0.5 and 2 g/L were added at the onset of tea infusion and to the fresh, unpasteurized kombucha. The addition of hops (particularly at the pre-fermentation stage of production) led to a significant decrease in radical formation in the produced kombucha measured by electron spin resonance spectroscopy (ESR), which correlated with the higher DPPH antiradical activity and the elevated bitter α-acid content. From the sensory perspective, the post-fermentation addition of hops to kombucha resulted in a significantly higher rating of the overall quality. This enhancement was directly associated with heightened bitterness, increased presence of fruity and citrusy aromas, and a simultaneous reduction in the intensities of acetic and tea-related attributes. The data presented in this study are relevant for kombucha producers, who want to deliver a sensory-novel product in combination with an improved oxidative stability. Key points • Hop addition in kombucha production improves the antioxidative activity of the beverage. • Hop α-acids display higher antioxidative properties in kombucha than polyphenols. • Oxidative stability of kombucha fortified with hops depends on the timing of hops addition. • Hop addition enriches the taste and aroma attributes of kombucha.