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The flavonoid hesperidin and its aglycone are widely recognized for their functionality, wherein bioavailability is the key to ensuring their bio-efficacy for diverse health benefits. The aim of the present study was to evaluate the pharmacokinetics of a inclusion complex of hesperetin-7-O-glucoside with β-cyclodextrin (HEPT7G/βCD) in Sprague-Dawley (SD) rats, and in a randomized, double-blind, placebo-controlled, and crossover study in healthy human subjects. A significantly higher bioavailability (P < 0.01) of hesperetin metabolites derived from the HEPT7G/βCD inclusion complex compared with hesperetin-lecithin (Peretin-D) and α-monoglucosyl hesperidin formulations was observed in SD rats administered with identical doses by oral gavage feeding. Furthermore, in healthy human subjects, an acute single dose of the HEPT7G/βCD inclusion complex significantly enhanced the plasma hesperetin metabolites concentration (P < 0.001) and displayed an improved pharmacokinetic profile (P < 0.001) compared to an identical dose of hesperetin from hesperidin in maltodextrin (placebo: HES-Dex). The Tmax was nearly 10-fold faster (P = 0.016) after subjects consumed the HEPT7G/βCD inclusion complex compared with HES-Dex, and the MRT was significantly lowered (P = 0.011), respectively. Results also indicated the absence of any sequence (order effect) and period effect. No adverse effects were reported, and no clinically significant changes were noticed in blood biochemical markers. The oral intake of the HEPT7G/βCD inclusion complex in human subjects was well tolerated and safe. In summary, the bioavailability of hesperetin metabolites was regulated with HEPT7G/βCD inclusion complex consumption due to shifting the absorption site from the colonocyte to the enterocyte, and probably due to higher -2R enantiomer content. Such modulation of metabolites may be beneficial for regulating the biological functions of the dietary HEPT7G/βCD inclusion complex when used in foods, functional beverages, dietary supplements, and nutraceuticals.

Dose-response of prebiotic partially hydrolyzed guar gum (PHGG) dietary fiber supports the gut microbiome abundance and improves gastrointestinal health, which is imperative for healthy skin. In this 12 week of open-label randomized, paralleled, and controlled study, we investigated the role of PHGG on skin barrier function including the measurements of the stratum corneum hydration levels using the non-invasive electrical methods along with a questionnaire to determine near-surface hydration distribution, micro-topography and texture properties of the skin. Healthy male and female volunteers (N = 49; M 34 & F 15; mean age: 35.6 ± 3.2 years) were recruited. Study subjects were randomized into three groups (U0: non-ingestion; U1: 6 g/day PHGG; and U2: 12 g/day PHGG). The moisture content of the skin stratum corneum and skin texture parameters were determined at baseline (0 W), after 4 weeks (4 W), 8 weeks (8 W), and 12 weeks (12 W). The result indicates ingestion of 6 and 12 g/day PHGG dietary fiber helps maintain a constant moisture level in the surface skin stratum corneum (i.e. prevents drying skin conditions) during seasonal fluctuations. An amelioration of bowel movement reported in the study may show a link between improved gut environment and increased hydration level of the skin stratum corneum that prevents dryness, roughness, and textural disorder to the skin during winter conditions. In summary, the consumption of prebiotic PHGG dietary fiber could be pivotal to increased formation of bacterially produced metabolites that strengthen the skin integrity and regulate the moisture content of the skin stratum corneum.

Iron is specifically important to athletes, and attention has grown to the association between sports performance and iron regulation in the daily diets of athletes. The study presents new insights into stress, mood states, fatigue, and sweating behavior among the non-anemic athletes with sweating exercise habits who consumed a routine low dose (3.6 mg/day) of iron supplementation. In this double-blind, randomized, placebo-controlled, parallel-group study, both non-anemic male (N = 51) and female (N = 42) athletes were supplemented either with a known highly bioavailable iron formulation (SunActive® Fe) or placebo during the follow-up training exercise period over four weeks at their respective designated clinical sites. The effect of oral iron consumption was examined on fatigue, stress profiles, as well as the quality of life using the profile of mood state (POMS) test or a visual analog scale (VAS) questionnaire, followed by an exercise and well-being related fatigue-sweat. Also, their monotonic association with stress biomarkers (salivary α-amylase, salivary cortisol, and salivary immunoglobulin A) were determined using spearman's rank correlation coefficient test. Repeated measure multivariate analysis of variance (group by time) revealed that the total mood disturbance (TMD) score was significantly lower (P = 0.016; F = 6.26) between placebo and iron supplementation groups over the four weeks study period among female athletes. Also, a significant reduction in tired feeling/exhaustion after the exercise (P = 0.05; F = 4.07) between the placebo and iron intake groups was noticed. A significant within-group reduction (P ≤ 0.05) was noticed in the degree of sweat among both male and female athletes after 2 and 4 weeks of iron supplementation, while athletes of the placebo intake group experienced a non-significant within-group reduction in the degree of sweat. Overall, the result indicates routine use of low dose (3.6 mg/day) iron supplementation is beneficial for non-anemic endurance athletes to improve stress, mood states, subjective fatigue, and sweating conditions.

Isoquercitrin has a higher bioavailability than quercetin and has various pharmacological effects. In the present study, we aim to elucidate the structure of the novel isoquercitrin-γ-cyclodextrin (IQC-γCD) inclusion complex derived through controlled enzymatic hydrolysis of rutin into isoquercitrin in-situ included in γ-cyclodextrin. Several vibrational, electronic and analytical spectral measurement techniques (FTIR, 1H-NMR, 13C-NMR, UV-Vis, DSC, PXRD, Raman spectroscopy, and SEM) were employed. The detailed structural comparison of the IQC-γCD inclusion complex with isolated isoquercitrin revealed the shielding of isoquercitrin –OH groups inside the γ-CD cavity, and thus, confirmed the successful formation of the inclusion complex that exhibit distinct spectroscopic features from both guest and host molecules. The phase-solubility studies showed that isoquercitrin formed a 1:1 stoichiometric inclusion complex with γ-CD. The aqueous solubility of isoquercitrin was significantly enhanced by complexation with γ-CD complex possibly due to increased isoquercitrin dissolution rate compared to the isolated isoquercitrin. The IQC-γCD inclusion could have enhanced pharmacokinetics that will be useful for future applications in functional foods and health benefits.

Isoquercitrin has been drawing increasing commercial concern since it has better bioavailability than quercetin and displays a wide range of in-vivo and in-vitro pharmacological effects. The main objective of the present study was to evaluate the pharmacokinetics of the IQC-γCD inclusion complex in Sprague-Dawley (SD) rats and in a controlled non-randomized, double-blind, and crossover study among the healthy volunteers. For instance, in SD rats administrated with IQC-γCD formulation by oral gavage feeding (0.05 mM/Kg body weight) showed significantly higher bioavailability (P

Flavonoids are biologically active natural products of great interest for their potential applications in functional foods and pharmaceuticals. A hesperetin-7-O-glucoside inclusion complex with β-cyclodextrin (HEPT7G/βCD; SunActive® HCD) was formulated via the controlled enzymatic hydrolysis of hesperidin with naringinase enzyme. The conversion rate was nearly 98%, estimated using high-performance liquid chromatography analysis. The objective of this study was to investigate the stability, solubility, and spectroscopic features of the HEPT7G/βCD inclusion complex using Fourier-transform infrared (FTIR), Raman, ultraviolet–visible absorption (UV–vis), 1H- and 13C- nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC–MS), scanning electron microscopy (SEM), and powdered X-ray diffraction (PXRD) spectroscopic techniques including zeta potential, Job’s plot, and phase solubility measurements. The effects of complexation on the profiles of supramolecular interactions in analytic features, especially the chemical shifts of β-CD protons in the presence of the HEPT7G moiety, were evaluated. The stoichiometric ratio, stability, and solubility constants (binding affinity) describe the extent of complexation of a soluble complex in 1:1 stoichiometry that exhibits a greater affinity and fits better into the β-CD inner cavity. The NMR spectroscopy results identified two different configurations of the HEPT7G moiety and revealed that the HEPT7G/βCD inclusion complex has both –2S and –2R stereoisomers of hesperetin-7-O-glucoside possibly in the –2S/–2R epimeric ratio of 1/1.43 (i.e., –2S: 41.1% and –2R: 58.9%). The study indicated that encapsulation of the HEPT7G moiety in β-CD is complete inclusion, wherein both ends of HEPT7G are included in the β-CD inner hydrophobic cavity. The results showed that the water solubility and thermal stability of HEPT7G were apparently increased in the inclusion complex with β-CD. This could potentially lead to increased bioavailability of HEPT7G and enhanced health benefits of this flavonoid.

The gut microbiomes association towards a favorable health profile is a rapidly emerging active area of research. This randomized, double-blind, crossover, placebo-controlled study elucidates the impact of prebiotic partially hydrolyzed guar gum (PHGG) dietary fiber on the relative abundance of the gut microbiomes (16S rRNA gene sequencing) and their significant correlation with fecal defecation characteristics among healthy male athletes. Subjects followed a daily six grams dietary intake of either PHGG or placebo for four weeks, following a three weeks washout period, subjects followed another four weeks of crossover alternative administration. Fecal defecation characteristics were assessed using a questionnaire along with quality of life (QOL) questions. The results demonstrated that genus level alteration in gastrointestinal microbiomes relative abundance was correlated to representative changes in fecal defecation characteristics, especially in reduction of diarrhea (P = 0.035) and fecal excretory feeling (P = 0.038). The PHGG intake led to a significant increase in phylum Actinobacterium (P = 0.04), along with a significant decrease in Bacteroidetes (P = 0.036). Also, a trending decrease in Firmicutes (P = 0.09) was noticed. At genus level, a significant alteration in the relative abundance of Bifidobacterium (P = 0.047) and Clostridium subcluster XI (P = 0.044) were observed with PHGG intake compared with placebo. Reduction in diarrhea was associated with the relative abundance of phylum Firmicutes/Bacteroidetes ratio and genera Bacteroides/Prevotella ratio for the PHGG intervention compared to placebo. In summary, the finding reveals that even at relatively low dosage, intake of prebiotic PHGG dietary fiber modulates gastrointestinal microbiomes, and thus improves gut health.

Catechins are a part of the chemical family of flavonoids, a naturally occurring antioxidant, and a secondary metabolite in certain plants. Green tea catechins are well recognized for their essential anti-inflammatory, photo-protective, antioxidant, and chemo-preventive functions. Ultraviolet radiation is a principal cause of damage to the skin. Studies observed that regular intake of green tea catechins increased the minimal dose of radiation required to induce erythema. The objectives of this systematic review and meta-analysis are to determine the effectiveness of green tea catechins in cutaneous erythema and elucidate whether green tea catechin consumption protects against erythema (sunburn) inflammation. A comprehensive literature search was conducted to identify the relevant studies. Two researchers carried out independent screening, data extraction, and quality assessment according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The pooled effect of green tea catechins on protection against erythema was assessed using approaches fixed-effects or random-effects model to quantify the effectiveness of green tea catechins in the erythema dose–response. Studies not be included in meta-analyses were summarized narratively. Six randomized controlled studies of enrolled studies regularly administrated green tea catechins orally for 6 to 12 weeks involving healthy volunteers comprising a total of 100 participants were included in the analysis. The results revealed green tea catechins have favorable protection against erythema inflammation even at increased minimal erythema dose (MED) of ultraviolet radiation. Meta-analysis results confirm oral supplementation of green tea catechins is highly effective at low-intensity ultraviolet radiation-induced erythema response (MED range; 1.25–1.30) compared to placebo, showing a significant pooling difference (p = 0.002) in erythema index (SMD: −0.35; 95% CI, −0.57 to −0.13; I2 = 4%, p = 0.40) in the random-effects model. The pro-inflammatory signaling pathways through oral supplementation with green tea catechins are an attractive strategy for photo-protection in healthy human subjects and could represent a complementary approach to topical sunscreens. Therefore, studies that involved green tea catechin in topical applications to human subjects were also evaluated separately, and their meta-analysis is presented as a reference. The evidence indicates that regular green tea catechin supplementation is associated with protection against UV-induced damage due to erythema inflammation.

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Identification of reproducible biomarker(s) to facilitate longitudinal monitoring of disease progression and provide readouts for therapeutic response has remained elusive. One factor that has complicated the identification of suitable biomarkers in this mouse model has been that variations in animal husbandry appear to significantly influence readouts. In the current study, we cross-compared a number of biological parameters in blood from Cln3Δex7/8 mice and control, non-disease mice on the same genetic background from multiple animal facilities in an attempt to better define a surrogate marker of CLN3-Batten disease. Interestingly, we found that significant differences between Batten and non-disease mice found at one site were generally not maintained across different facilities. Our results suggest that colony variation in the Cln3Δex7/8 mouse model of CLN3-Batten disease can influence potential biomarkers of the disease.

The preventive efficacies and safety of Emblica Officinalis Gatertn (Amla), a most important and extensively studied plant in the traditional Indian Ayurvedic system of medicine, are presented. Eligible healthy adult subjects (n = 15) were randomized to receive either amla or placebo (500 mg per day) during an 18-week study. The efficacy parameters evaluated were the vascular function, blood hematology, oxidative and inflammatory biomarkers, glucose and lipid profiles, urinalysis, and liver hepatotoxicity. The amla intake showed significant improvements in the primary efficacy parameter of blood fluidity. There were also improvements in the secondary endpoints including lowering of von Willebrand factor (vWF), reduced 8-hydroxy-2'-deoxyguanosine (8-OHdG) as well as thrombin (TM) biomarkers of oxidative stress along with a significant improvement in HDL-cholesterol and lowering the LDL-cholesterol levels. No substantial changes were observed in liver hepatotoxicity, urinalysis, and hematology after consumption of amla compared to baseline or placebo. In addition, no adverse events, changes safety parameters or tolerance issues were observed after consumption of amla. In conclusion, amla supplementation showed acceptable palatability, improved endothelial functions and reduced oxidative stress., (© 2019 The Author(s).)