Pharmacokinetics of a Single Dose of Turmeric Curcuminoids Depends on Formulation: Results of a Human Crossover Study.

BACKGROUND: Curcuminoids from turmeric rhizome have significant health benefits but low bioavailability. OBJECTIVES: To assess the pharmacokinetics of a novel natural turmeric dried colloidal suspension compared with 4 other turmeric formulations (including a standardized extract) at their respective recommended dosages. METHODS: Thirty healthy men and women (18 to 45 y old) were enrolled in a randomized, open-labeled, crossover trial, and sequentially consumed single oral doses of standard turmeric extract (1500 mg), liquid micellar preparation (1000 mg), piperine-curcuminoid combination (1515 mg), phytosome formulation (1000 mg), or the dried colloidal suspension (300 mg). Eleven blood samples were obtained over 24 h, plasma was extracted with or without deconjugation with ß-glucuronidase or sulfatase, and ultra-high-pressure liquid chromatography/tandem MS was used to quantify the 3 parent curcuminoids and 12 metabolites. Classical pharmacokinetics parameters were derived. RESULTS: The total AUC values of unconjugated curcuminoids were highly variable within participants, with no significant differences between formulations. However, the AUC values for total curcuminoids (including all metabolites) showed significant product effects. Indeed, the micellar preparation delivered higher levels of total curcuminoids than any other formulation (8540 ng·h/mL), reaching significance when compared with the dried colloidal suspension and standard extract (6520 and 5080 ng·h/mL, respectively). After dose normalization, both micellar and dried colloidal formulations showed significantly higher AUC levels than the standard extract (respectively 136 and 72.9, compared with 3.7 ng·h/mL/mg). Total curcuminoid absorption levels were also significantly higher for the dried colloidal suspension when compared with either piperine or phytosome formulations. Interestingly, no significant differences were observed between the piperine-curcuminoid combination and the standard extract. No serious adverse events were reported. CONCLUSIONS: The administration of a low dose of the novel natural dried colloidal suspension provided high unconjugated and conjugated curcuminoid absorption, with significant beneficial differences when compared with the high dose of standard extract.This trial was registered at clinicaltrials.gov as NCT03621865.

para-Menthane as a Stable Terpene Derived from Orange By-Products as a Novel Solvent for Green Extraction and Solubilization of Natural Substances.

This study aims at investigating p-menthane, a novel bio-based solvent resulting from the hydrogenation of d-limonene, as a green alternative to n-hexane or toluene for the extraction and solubilization of natural substances. First, conductor-like combination of quantum chemistry (COSMO) coupled with statistical thermodynamics (RS) calculations show a comparable solubilization profile of p-menthane and n-hexane for carotene, volatile monoterpenes such as carvone and limonene, and model triglycerides. Other data obtained experimentally in solid/liquid extraction conditions further indicate that p-menthane showed similar performances to n-hexane for extracting carotenes from carrots, aromas from caraway seeds, and oils from rapeseeds, as these products showed a comparable composition. p-Menthane was also tested using common analytical extraction procedures such as Soxhlet for determination of oil content via multiple extraction stages, and Dean-Stark for determination of water content via azeotropic distillation. For both systems, yields were comparable, but for Dean-Stark, the distillation curve slope was higher when using p-menthane, and the time needed to attain 100% water recovery was 55% shorter than for toluene. Taken together, these results reveal the potential of p-menthane as a green replacer for petroleum-based solvents such as n-hexane or toluene.

What is the best ethanol-water ratio for the extraction of antioxidants from rosemary? Impact of the solvent on yield, composition, and activity of the extracts.

Extracts rich in antioxidants, such as rosemary extracts, are currently obtained by extraction of the plant material using hydro-alcoholic mixtures with high ethanol content. As this ratio is generally chosen by default and scarcely optimized, we intended to investigate the impact of the hydro-alcoholic composition on extract characteristics such as extraction yield, composition profile in selected compounds, and antioxidant/reducing activity such as Folin-Ciocalteu, DPPH, and ORAC. A theoretical determination of rosmarinic (RA) and carnosic (CA) acid solubilities in ethanol:water mixtures was also performed using COSMO-RS and was confronted to experiments. While the best solubilizing solvent (100% ethanol) was also the best extracting solvent for CA, it was not the case with RA since pure ethanol appeared as a poor solvent compared to 30% ethanol which was optimal. Finally, the best antioxidant activities were obtained with 30% ethanol.

Effect of a Hop Extract Standardized in 8-Prenylnaringenin on Bone Health and Gut Microbiome in Postmenopausal Women with Osteopenia: A One-Year Randomized, Double-Blind, Placebo-Controlled Trial.

Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blind, placebo-controlled, randomized trial, 100 postmenopausal, osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and either a hop extract (HE) standardized in 8-PN (n = 50) or a placebo (n = 50) for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed by DXA measurements and plasma bone biomarkers, respectively. Participant's quality of life (SF-36), gut microbiome composition, and short-chain fatty acid (SCFA) levels were also investigated. In addition to the CaD supplements, 48 weeks of HE supplementation increased total body BMD (1.8 ± 0.4% vs. baseline, p < 0.0001; 1.0 ± 0.6% vs. placebo, p = 0.08), with a higher proportion of women experiencing an increase ≥1% compared to placebo (odds ratio: 2.41 ± 1.07, p < 0.05). An increase in the SF-36 physical functioning score was observed with HE versus placebo (p = 0.05). Gut microbiome α-diversity and SCFA levels did not differ between groups. However, a higher abundance of genera Turicibacter and Shigella was observed in the HE group; both genera have been previously identified as associated with total body BMD. These results suggest that an 8-PN standardized hop extract could beneficially impact bone health of postmenopausal women with osteopenia.

Natural particles can armor emulsions against lipid oxidation and coalescence.

Traditional functional ingredients, such as conventional emulsifiers (surfactants, animal-derived proteins), and synthetic antioxidants may become obsolete in the development of clean-label, plant-based, sustainable food emulsions. Previously, we showed that tailor-made antioxidant-loaded particles can yield both physically and oxidatively stable emulsions, and we expected that natural particles with related properties could also show these beneficial effects. Here, we investigated Pickering emulsions prepared with natural plant particulate materials. Particles that showed weak aggregation in acidic aqueous media, indicating a relatively hydrophobic surface, were able to physically stabilize oil-in-water emulsions, through either Pickering stabilization (powders of matcha tea, spinach leaves, and spirulina cake), or an increase in viscosity (pineapple fibers). Matcha tea and spinach leaf particle-stabilized emulsions were highly stable to lipid oxidation, as compared to emulsions stabilized by conventional emulsifiers. Taking this dual particle functionality as a starting point for emulsion design is, in our view, essential to achieve clean-label food emulsions.

Genipap (Genipa americana L.) juice intake biomarkers after medium-term consumption.

Genipap (Genipa americana L.) is an exotic fruit largely consumed and well known, in Amazonian pharmacopeia, to treat anemia, measles and uterine cancer. It is also used as a diuretic, digestive, healing, laxative and antiseptic. The aim of this study was to apply an untargeted metabolomics strategy to determine biomarkers of food intake after short-term consumption of genipap juice. Sixteen healthy adult men were administered jenipap juice (250 mL) twice a day for three weeks. Before and after the three weeks of consumption. the subjects drank a control drink, and they consumed a standard diet. Urine was collected after 0-6 h, 6-12 h and 12-24 h. An ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics approach was applied to analyze the urine samples. Principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed to highlight experimental differences between groups. The value of the area under the curve (AUC) of the receiver operator characteristic (ROC) curve validated the identified biomarkers. Thirty-one statistically affected urinary metabolites were putatively identified and were mainly related to iridoids family, medium-chain fatty acids, and polyphenols. Also a group of urinary markers including dihydrocaffeic acid (DHCA), 1-(4-hydroxyphenyl)-1,2-propanediol and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were established as biomarkers of genipap consumption. Our findings have established a comprehensive panel of changes in the urinary metabolome and provided information to monitor endogenous alterations that are linked to genipap juice intake. These data should be used in further studies to understand the health implications of genipap juice consumption.

Sinapine, but not sinapic acid, counteracts mitochondrial oxidative stress in cardiomyocytes.

INTRODUCTION: When confronted to stress or pathological conditions, the mitochondria overproduce reactive species that participate in the cellular dysfunction. These organelles are however difficult to target with antioxidants. A feature of mitochondria that can be used for this is the negatively charged compartments they form. Most of mitochondrion-targeting antioxidants are therefore cationic synthetic molecules. Our hypothesis is that such mitochondriotropic traits might also exists in natural molecules. AIM: We tested here whether sinapine, a natural phenolic antioxidant-bearing a permanent positive charge, can target mitochondria to modulate mitochondrial oxidative stress. METHODS: Experiments were performed in-vitro, in-cellulo, ex-vivo, and in-vivo, using cardiac tissue. The sinapic acid -lacking the positively-charged-choline-moiety present in sinapine-was used as a control. Sinapine entry into mitochondria was investigated in-vivo and in cardiomyocytes. We used fluorescent probes to detect cytosolic (H2DCFDA) and mitochondrial (DHR123) oxidative stress on cardiomyocytes induced with either hydrogen peroxide (H2O2) or antimycin A, respectively. Finally, ROS production was measured with DHE 10 min after ischemia-reperfusion (IR) on isolated heart, treated or not with sinapine, sinapic acid or with a known synthetic mitochondrion-targeted antioxidant (mitoTempo). RESULTS: We detected the presence of sinapine within mitochondria in-vitro, after incubation of isolated cardiomyocytes, and in-vivo, after oral treatment. The presence of sinapic acid was not detected in the mitochondria. Both the sinapine and the sinapic acid limited cytosolic oxidative stress in response to H2O2. Only sinapine was able to blunt oxidative stress resulting from antimycin A-induced mtROS. Both mitoTempo and sinapine improved cardiac functional recovery following IR. This was associated with lower ROS production within the cardiac tissue. CONCLUSION: Sinapine, a natural cationic hydrophilic phenol, commonly and substantially found in rapeseed species, effectively (i) enters within the mitochondria, (ii) selectively decreases the level of mitochondrial oxidative stress and, (iii) efficiently limits ROS production during cardiac ischemia-reperfusion.

Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake.

Genipap (Genipa americana L.) is a native fruit from Amazonia that contains bioactive compounds with a wide range of bioactivities. However, the response to genipap juice ingestion in the human exposome has never been studied. To identify biomarkers of genipap exposure, the untargeted metabolomics approach in human urine was applied. Urine samples from 16 healthy male volunteers, before and after drinking genipap juice, were analyzed by liquid chromatography⁻high-resolution mass spectrometry. XCMS package was used for data processing in the R environment and t-tests were applied on log-transformed and Pareto-scaled data to select the significant metabolites. The principal component analysis (PCA) score plots showed a clear distinction between experimental groups. Thirty-three metabolites were putatively annotated and the most discriminant were mainly related to the metabolic pathways of iridoids and phenolic derivatives. For the first time, the bioavailability of genipap iridoids after human consumption is reported. Dihydroxyhydrocinnamic acid, (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate, hydroxyhydrocinnamic acid, genipic acid, 12-demethylated-8-hydroxygenipinic acid, 3(7)-dehydrogenipinic acid, genipic acid glucuronide, nonate, and 3,4-dihydroxyphenylacetate may be considered biomarkers of genipap consumption. Human exposure to genipap reveals the production of derivative forms of bioactive compounds such as genipic and genipinic acid. These findings suggest that genipap consumption triggers effects on metabolic signatures.

Rapid, cost-effective and accurate quantification of Yucca schidigera Roezl. steroidal saponins using HPLC-ELSD method.

Yucca GRAS-labelled saponins have been and are increasingly used in food/feed, pharmaceutical or cosmetic industries. Existing techniques presently used for Yucca steroidal saponin quantification remain either inaccurate and misleading or accurate but time consuming and cost prohibitive. The method reported here addresses all of the above challenges. HPLC/ELSD technique is an accurate and reliable method that yields results of appropriate repeatability and reproducibility. This method does not over- or under-estimate levels of steroidal saponins. HPLC/ELSD method does not require each and every pure standard of saponins, to quantify the group of steroidal saponins. The method is a time- and cost-effective technique that is suitable for routine industrial analyses. HPLC/ELSD methods yield a saponin fingerprints specific to the plant species. As the method is capable of distinguishing saponin profiles from taxonomically distant species, it can unravel plant adulteration issues.