Chemical and genetic basis of orange flavor.

Sweet orange (Citrus sinensis) exhibits limited genetic diversity and high susceptibility to Huanglongbing (HLB). Breeding HLB-tolerant orange-like hybrids is in dire need. However, our understanding of the key compounds responsible for orange flavor and their genetic regulation remains elusive. Evaluating 179 juice samples, including oranges, mandarins, Poncirus trifoliata, and hybrids, distinct volatile compositions were found. A random forest model predicted untrained samples with 78% accuracy and identified 26 compounds crucial for orange flavor. Notably, seven esters differentiated orange from mandarin flavor. Cluster analysis showed six esters with shared genetic control. Differential gene expression analysis identified C. sinensis alcohol acyltransferase 1 (CsAAT1) responsible for ester production in orange. Its activity was validated through overexpression assays. Phylogeny revealed the functional allele was inherited from pummelo. A SNP-based DNA marker in the coding region accurately predicted phenotypes. This study enhances our understanding of orange flavor compounds and their biosynthetic pathways and expands breeding options for orange-like cultivars.

A combination of rebaudioside A and neohesperidin dihydrochalcone suppressed weight gain by regulating visceral fat and hepatic lipid metabolism in ob/ob mice.

Rebaudioside A (Reb A) and neohesperidin dihydrochalcone (NHDC) are known as intense sweeteners. This study aimed to examine the anti-obesity effects of Reb A and NHDC. C57BL/6 J-ob/ob mice were supplemented with Reb A (50 mg/kg body weight [b.w.]), NHDC (100 mg/kg b.w.), or their combination (COMB) for 4 weeks. COMB-supplemented mice showed significant reduction in b.w. gain, food efficiency ratio, and fat mass. Additionally, mice in the COMB group showed suppressed levels of genes related to adipogenesis, lipogenesis, and lipolysis in the perirenal fat and the levels of hepatic triglyceride, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase. The lipogenesis and pro-inflammatory gene expressions were also downregulated in the liver, whereas ß-oxidation related genes were upregulated in the COMB group. In addition, mice that received COMB showed distinct gut microbiota structure, enriched in Blautia and Parabacteroides, and depleted in Faecalibaculum and Mucispirillum, in relation to the control group. These results suggest that supplementation with Reb A and NHDC may be an effective treatment for obesity-related metabolic disorders. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01391-1.

Sensory quality of Citrus scion hybrids with Poncirus trifoliata in their pedigrees.

Hybrids of Poncirus trifoliata L. Raf. with Citrus have shown degrees of tolerance to the deadly citrus greening disease, hence prompting interest as potential commercial varieties. Although P. trifoliata is known to produce fruit that is inedible, fruit from many advanced hybrid trees have not been evaluated for their quality potential. The sensory quality of selected Citrus hybrids with varying degrees of P. trifoliata in their pedigrees is reported herein. Four Citrus × P. trifoliata hybrids developed through the USDA Citrus scion breeding program-1-76-100, 1-77-105, 5-18-24, and 5-18-31-had acceptable eating quality and sweet and sour taste, with mandarin, orange, fruity-noncitrus, and floral flavors. On the other hand, hybrids with higher proportion of P. trifoliata in their pedigrees, US 119 and 6-23-20, produced a juice characterized by green, cooked, bitter, and Poncirus-like flavor and aftertaste. Partial least square regressions revealed that the Poncirus-like off-flavor is likely due to a combination of higher than typical amounts of sesquiterpene hydrocarbons (woody/green odor), monoterpenes (citrus/pine), and terpene esters (floral) and a lack of aldehydes with typical citrus odor (octanal, nonanal, and decanal). Sweetness and sourness were mostly explained by high sugars and acids, respectively. Further, carvones and linalool contributed to sweetness in the samples from early and late seasons, respectively. In addition to highlighting chemical contributors to sensory descriptors in Citrus × P. trifoliata hybrids, this study provides useful information on sensory quality for future citrus breeding efforts. PRACTICAL APPLICATION: The relationships between the sensory quality and secondary metabolites of Citrus × P. trifoliata hybrids described in this study help identify disease-resistant Citrus scion hybrids with acceptable flavor and help mobilize this resistance in future breeding efforts. It also shows potential of such hybrids to be commercialized.

Influences of Solubility and Vehicle Carriers on Eriodictyol Pharmacokinetics in Rats.

In this study, the pharmacokinetics of oral doses of eriodictyol in 1% sodium carboxymethylcellulose and in saline/PEG400/Tween80 (75/20/5, v/v/v) in rats were compared. The pharmacokinetics of eriocitrin administered as a dissolved solution in water were also characterized. Metabolites of eriodictyol and eriocitrin in whole blood consisted mainly of eriodictyol, homoeriodictyol, and hesperetin glucuronides and ring-fission metabolites. In whole blood, no free nonconjugated flavanone aglycones were detected. Significant differences were observed in the pharmacokinetics of eriodictyol administered as a suspension in 1% sodium carboxymethylcellulose versus administration as a dissolved solution in saline/PEG400/Tween80 (75/20/5, v/v/v). At a dose of 25 mg kg-1 eriodictyol administered with 1% sodium carboxymethylcellulose, a biphasic pharmacokinetic curve was observed, while only a single concentration peak was observed following an administration of 25 mg kg-1 eriodictyol dissolved in saline/PEG400/Tween80 (75/20/5, v/v/v). For all trials, the pharmacokinetics of eriodictyol differed from those of eriocitrin dissolved in water.

Neohesperidin Dihydrochalcone and Neohesperidin Dihydrochalcone-O-Glycoside Attenuate Subcutaneous Fat and Lipid Accumulation by Regulating PI3K/AKT/mTOR Pathway In Vivo and In Vitro.

Neohesperidin dihydrochalcone (NHDC), a semi-natural compound from bitter orange, is an intense sweetener. The anti-obesity effects of NHDC and its glycosidic compound, NHDC-O-glycoside (GNHDC), were investigated. C57BLKS/J db/db mice were supplemented with NHDC or GNHDC (100 mg/kg b.w.) for 4 weeks. Body weight gain, subcutaneous tissues, and total adipose tissues (sum of perirenal, visceral, epididymal, and subcutaneous adipose tissue) were decreased in the NHDC and GNHDC groups. Fatty acid uptake, lipogenesis, and adipogenesis-related genes were decreased, whereas ß-oxidation and fat browning-related genes were up-regulated in the sweetener groups. Furthermore, both sweeteners suppressed the level of triacylglycerol accumulation, lipogenesis, adipogenesis, and proinflammatory cytokines in the 3T3-L1 cells. The PI3K/AKT/mTOR pathway was also down-regulated, and AMP-acttvated protein kinase (AMPK) was phosphorylated in the treatment groups. These results suggest that NHDC and GNHDC inhibited subcutaneous fat and lipid accumulation by regulating the PI3K/AKT/mTOR pathway and AMPK-related lipogenesis and fat browning.

Eriodictyol Suppresses Porphyromonas gingivalis-Induced Reactive Oxygen Species Production by Gingival Keratinocytes and the Inflammatory Response of Macrophages.

Porphyromonas gingivalis is a key pathogen of periodontitis, an inflammatory disease that affects the tooth-supporting tissues. The aim of the present study was to investigate the effects of the flavanone eriodictyol on P. gingivalis-induced reactive oxygen species (ROS) production by gingival keratinocytes and the inflammatory response of macrophages. Porphyromonas gingivalis and H2O2 acted synergistically to induce ROS production by keratinocytes. The presence of eriodictyol significantly attenuated ROS production in a dose-dependent manner. We used a macrophage model to show that eriodictyol decreases the secretion of IL-1ß, IL-6, IL-8, and TNF-α induced by P. gingivalis. Evidence has been brought that this anti-inflammatory property of eriodictyol may be related to its ability to prevent the activation of the NF-κB signaling pathway by P. gingivalis. This periodontal pathogen was also found to be a potent inducer of matrix metalloproteinase (MMP) production by macrophages, including MMP-2, MMP-8, and MMP-9. Eriodictyol dose-dependently inhibited the production of all three MMPs. Lastly, eriodictyol inhibited the catalytic activity of both MMP-9 and P. gingivalis collagenase. In conclusion, eriodictyol may be a potential therapeutic agent for preventing and/or treating periodontal disease due to its antioxidant, anti-inflammatory, and anti-proteinase properties.

Steam Explosion (STEX) of Citrus × Poncirus Hybrids with Exceptional Tolerance to Candidatus Liberibacter Asiaticus (CLas) as Useful Sources of Volatiles and Other Commercial Products.

Florida citrus production has declined 75% due to Huanglongbing (HLB), a disease caused by the pathogenic bacterium Candidatus Liberibacter asiaticus (CLas). Methods to combat CLas are costly and only partially effective. The cross-compatible species Poncirus trifoliata and some of its hybrids are known to be highly tolerant to CLas, and thus can potentially serve as an alternative feedstock for many citrus products. To further investigate the commercial potential of citrus hybrids, three citrus hybrids, US-802, US-897, and US-942, were studied for their potential as feedstocks for citrus co-products using steam explosion (STEX) followed by water extraction. Up to 93% of sugars were recovered. US-897 and US-942 have similar volatile profiles to that of the commercial citrus fruit types and as much as 85% of these volatiles could be recovered. Approximately 80% of the pectic hydrocolloids present in all three hybrids could be obtained in water washes of STEX material. Of the phenolics identified, the flavanone glycosides, i.e., naringin, neohesperidin, and poncirin were the most abundant quantitatively in these hybrids. The ability to extract a large percentage of these compounds, along with their inherent values, make US-802, US-897, and US-942 potentially viable feedstock sources for citrus co-products in the current HLB-blighted environment.

Analysis and Potential Value of Compounds Extracted From Star Ruby, Rio Red, and Ruby Red Grapefruit, and Grapefruit Juice Processing Residues via Steam Explosion.

Culled whole grapefruit (WG) and grapefruit juice processing residues (GP) are currently incorporated into low-cost animal feed. If individual chemical components found within these side streams could be recovered as high-value coproducts, this would improve the overall value of the grapefruit crop. In this study, pectic hydrocolloids, sugars, volatiles, phenolics, and flavonoids were extracted from Star Ruby, Rio Red, and Ruby Red GP and WG using a continuous pilot scale steam explosion system. Up to 97% of grapefruit juice oils and peel oils could be volatilized and contained 87-94% d-limonene. The recovery of pectin, as determined by galacturonic acid content, was between 2.06 and 2.72 g 100 g-1. Of the phenolics and flavonoids analyzed in this study, narirutin and naringin were extracted in the amounts of up to 10,000 and 67,000 µg g-1, respectively.

Correlation between in vitro binding activity of sweeteners to cloned human sweet taste receptor and sensory evaluation.

The human sweet taste receptor is a TAS1R2/TAS1R3 heterodimer. To investigate the correlation between the in vitro affinity of sweeteners with stably expressed human sweet taste receptor in HEK-293 cells and human sensory evaluation, the receptor-ligand activity of bulk (sucrose, D-fructose, and allulose) and high-intensity sweeteners (saccharin, rebaudioside A, rebaudioside M, and neohesperidin dihydrochalcone) was compared by analyzing the Ca2+ release. The relative potency of the sweeteners was identified over a wide concentration range for EC50s. Relative to sucrose, bulk sweeteners showed similar concentration ranges and potency, whereas high-intensity sweeteners exhibited lower concentration ranges and higher potency. The log of the calculated EC50 of each sweetener relative to sucrose by the in vitro affinity assay was positively correlated (r = 0.9943) with the molar relative sweetness reported in the previous literatures. These results suggested a good correlation between the in vitro activity assay of sweeteners and human sensory evaluation.

Impact of citrus flavonoid supplementation on inflammation in lipopolysaccharide-induced periodontal disease in mice.

In general, the consumption of flavonoid-rich foods may influence the control/dysregulation of the magnitude and duration of inflammation and oxidative stress, which are known to contribute to multiple pathologies. Information regarding the impact of citrus flavonoid dietary supplementation on periodontal disease is still scarce. Herein, we investigated whether a diet supplemented with eriocitrin and eriodictyol could alter the course of the inflammatory response associated with LPS-induced periodontal disease in mice. Sixty BALB/c mice received a standard diet or a diet supplemented with different concentrations of eriocitrin or eriodictyol. After 30 days of food supplementation, a solution containing LPS from Escherichia coli was injected into the gingival tissues three times per week for four weeks. Neutrophils, mononuclear cells and eosinophils were assessed using a severity analysis system in H&E-stained sections and modified picrosirius red. The activities of myeloperoxidase (MPO), a marker of granulocyte infiltration, and eosinophil peroxidase (EPO) were determined spectrophotometrically. The oxidative damage was determined by measuring the malondialdehyde (MDA) content and anti-oxidative activity through the assessment of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Interleukin (IL)-1ß, TNF-α, and IL-10 were quantified by multiplex immunoassay. Periodontal inflammation was significantly inhibited by citrus flavonoid supplementation, including reduced flatness of the gingival epithelium and chronic and acute inflammatory cell infiltration, as well as loss of connective tissue in the gingival papillae. Both eriocitrin and eriodictyol inhibited gingival IL-1ß and TNF-α and increased IL-10 secondary to periodontitis. Significant protection and decreased MPO and EPO activity were detected in the periodontal tissue of citrus flavonoid-treated animals. In comparison with the LPS group, SOD, CAT and GPx activities were increased, while the MDA content was reduced, indicating decreased oxidative damage. These results suggest that a diet supplemented with the citrus flavonoids eriocitrin or eriodictyol may aid in the prevention of periodontitis, representing a potential method to enhance local immunity and host defense.

Physiological effects of tangeretin and heptamethoxyflavone on obese C57BL/6J mice fed a high-fat diet and analyses of the metabolites originating from these two polymethoxylated flavones.

Two compounds from citrus peel, tangeretin (TAN) and 3',4',3,5,6,7,8-heptamethoxyflavone (HMF), were investigated for their abilities to repair metabolic damages caused by an high-fat diet (HFD) in C57BL/6J mice. In the first 4 weeks, mice were fed either a standard diet (11% kcal from fat) for the control group, or a HFD (45% kcal from fat) to establish obesity in three experimental groups. In the following 4 weeks, two groups receiving the HFD were supplemented with either TAN or HMF at daily doses of 100 mg/kg body weight, while the two remaining groups continued to receive the standard healthy diet or the nonsupplemented HFD. Four weeks of supplementation with TAN and HMF resulted in intermediate levels of blood serum glucose, leptin, resistin, and insulin resistance compared with the healthy control and the nonsupplemented HFD groups. Blood serum peroxidation (TBARS) levels were significantly lower in the TAN and HMF groups compared with the nonsupplemented HFD group. Several differences occurred in the physiological effects of HMF versus TAN. TAN, but not HMF, reduced adipocyte size in the mice with pre-existent obesity, while HMF, but not TAN, decreased fat accumulation in the liver and also significantly increased the levels of an anti-inflammatory cytokine, IL-10. In an analysis of the metabolites of TAN and HMF, several main classes occurred, including a new set of methylglucuronide conjugates. It is suggested that contrasts between the observed physiological effects of TAN and HMF may be attributable to the differences in numbers and chemical structures of TAN and HMF metabolites.

Extraction Method Affects Contents of Flavonoids and Carotenoids in Huanglongbing-Affected "Valencia" Orange Juice.

A previous study using healthy "Valencia" orange fruit found that juicing extraction methods dramatically changed the orange juice (OJ) flavor and phytochemical profiles. The present study was conducted to confirm whether the same changes occur when Huanglongbing (HLB)-affected oranges were used. HLB has extensively spread to most OJ processing regions around the world, substantially deteriorating fruit and juice flavor quality and altering the phytochemical profiles. In this study, the effect of two major juice extractor types, a shear force extractor (SFE) and a reamer extractor (RE), on the juice quality and physiochemical profile was assessed using HLB-affected orange fruit. Juice extracted via SFE resulted in a lower yield with lower peel oil and higher pellet (peel tissue particles) content compared to juice obtained via RE. The SFE juice also had higher levels of hesperidin and other flavonoid glycosides, mainly due to plentiful peel tissue particles. The SFE juice was also abundant in carotenoids due to a large amount of flavedo particles in the juice. On the other hand, polymethoxylated flavones occurred at higher concentrations in the RE juice, and this may be due to the higher peel oil content in this juice. The SFE juice was rich in flavonoid glycosides and carotenoids, which are associated with potential antioxidant properties; however, the extra portion of the phytonutrients mostly existed in the pellets and possibly had low bioavailability. The results obtained from the HLB-affected oranges are in agreement with the previous observations of healthy oranges.

Pharmacokinetics and Biodistribution of Eriocitrin in Rats.

Eriocitrin plays a role in the reduction of oxidative stress and inflammation linked to the development of diabetes mellitus and atherosclerosis. We investigated the pharmacokinetics and distribution of eriocitrin metabolites in rats orally administered with eriocitrin. Plasma, urine, and organs were collected at 12 different time points from 0 to 24 h and analyzed by HPLC-PDA-MS. For the first time, the metabolism and distribution of orally administered eriocitrin were shown. Nine metabolites of eriocitrin were identified in rat urine, and seven in various tissues (eriodictyol, homoeriodictyol, hesperetin, and glucuronidated metabolites), and preliminary identifications of these metabolites are suggested. Overall, eriocitrin metabolites were widely distributed in the rat tissues, where homoeriodictyol and homoeriodictyol-7-O-glucuronide were the major metabolites. The half-lives of the metabolites in plasma were between 3 and 3.2 h, and the total bioavailability of eriocitrin was less than 1%.

Microencapsulation of Tangeretin in a Citrus Pectin Mixture Matrix.

The objectives of this research were to microencapsulate tangeretin, and to evaluate the basic characteristics of the microcapsule products. Tangeretin is a polymethoxyflavone (PMF) which has been revealed to possess various health benefits and is abundant in tangerine and other citrus peels. Microencapsulation technology is widely employed in the food and pharmaceutical industries to exploit functional ingredients, cells, and enzymes. Spray drying is a frequently applied microencapsulation method because of its low cost and technical requirements. In this research, tangeretin dissolved at different concentrations in bergamot oil was microencapsulated in a citrus pectin/sodium alginate matrix. The resulting microcapsule powder showed promising physical and structural properties. The retention efficiency of tangeretin was greater at a concentration of 2.0% (98.92%) than at 0.2% (71.05%), probably due to the higher temperature of the emulsion during the homogenizing and spray-drying processes. Encapsulation efficiency was reduced with increased concentration of tangeretin. Our results indicate that tangeretin could be successfully encapsulated within a citrus pectin/sodium alginate matrix using bergamot oil as a carrier.

Phenolics, flavonoids and antioxidant capacities in Citrus species with different degree of tolerance to Huanglongbing.

Huanglongbing (HLB) is a highly destructive disease to the citrus industry in Florida caused by the bacterium, Candidatus Liberibacter asiaticus(CLas) and is transmitted by Diaphorina citri. It is hypothesized that plants with high phenolic contents show higher tolerance to certain plant pathogens. In this regard, different citrus varieties and plants of genera related to Citrus were analyzed for their total phenolic and flavonoids contents, and their antioxidant capacities. In addition, the secondary metabolites in the leaves of seven citrus species were analyzed using high performance liquid chromatography-mass spectrometry (HPLC-MS). Colorimetric assays showed that curry leaf contained the highest total phenolic content and free radical scavenging activity (DPPH). Curry leaf also contained high concentrations of an unusual class of carbazole alkaloids. Tolerant Citrus species contained high levels of phenolics and flavonoids and showed high antioxidant capacities. Our results suggest that high phenolic and flavonoid leaf contents correlate with increased citrus tolerance to CLas bacterium. The results also suggest that the high level of carbazole alkaloids, known for their strong antimicrobial properties in curry leaf, could make it immune to the CLas bacteria. Understanding the mechanisms underpinning citrus tolerance to HLB will contribute to the development of commercially tolerant citrus cultivars.

Quercus leaf extracts display curative effects against Candidatus Liberibacter asiaticus that restore leaf physiological parameters in HLB-affected citrus trees.

Citrus greening, also called Huanglongbing (HLB), is one of the most destructive citrus diseases worldwide. It is caused by the fastidious gram-negative α-proteobacteria bacterium Candidatus Liberibacter asiaticus (CLas) and vectored by the Asian citrus psyllid (ACP), Diaphorina citri. Currently, there is no cure for HLB, no compounds have been successful in controlling HLB, and no sustainable management practices have been established for the disease. Thus, searching for alternative citrus greening disease mitigation strategies is considered an urgent priority for a sustainable citrus industry. The aim of this study was to use compounds extracted from oak, Quercus hemisphaerica, and to assess the antibacterial effects of these against CLas-infected citrus plants. The application of aqueous oak leaf extracts showed substantial inhibitory effects against CLas in citrus plants and the activity of genes related to starch. Significant differences were also observed in plant phenotypic and physiological traits after treatments. Citrus plants treated with oak extracts displayed an increase in stomatal conductance, chlorophyll content and nutrient uptake concurrently with a reduction of CLas titer, when compared to citrus plants treated with just water. The information provided from this study suggests a new management treatment program to effectively deal with the HLB disease.

Mitigation of Off-Flavor in Huanglongbing-Affected Orange Juice Using Natural Citrus Non-Volatile Compounds.

Huanglongbing (HLB) disease has reduced orange yield and flavor quality in Florida. Orange juice (OJ) and peel molasses (PM) compounds are "from the named fruit" (FTNF) and were tested for their effects on HLB-affected OJ taste. These and other "target" compounds, reportedly found in citrus, were spiked into off-flavored, HLB-affected reference juices. The spiked juice was evaluated by a sensory panel in comparison with unspiked juice for "sweetness", "sourness", "bitterness", "astringency", and "aftertaste". Of the target compounds, feruloyl putrescine, taxifolin, and neodiosmin most effectively reduced "bitterness", feruloyl putrescine reduced "astringency" and "aftertaste", while feruloyl putrescine and neodiosmin enhanced perceived "sweetness", perhaps due to reduced bitterness. OJ and PM fractions containing reported bitter limonoids, hydroxycinnamates, hesperidin, and/or polymethoxylated flavones enhanced "sourness', "bitterness", "astringency", and "aftertaste", and/or suppressed perceived "sweetness" (perhaps due to enhanced bitterness). Other fractions, containing feruloyl putrescine and/or vicenin-2 enhanced "sweetness" and reduced "bitterness", "sourness", "astringency", and/or "aftertaste". These potentially FTNF compounds may be useful for management of HLB-affected OJ juice flavor.

Detection of Phenylpropanoids in Citrus Leaves Produced in Response to Xanthomonas citri subsp. citri.

Citrus canker (CC), caused by the bacterial pathogen Xanthomonas citri subsp. citri, impacts citrus production in many areas of the world by reducing yields, degrading tree health, and severely blemishing the outer peels of fresh fruit. The relative susceptibility to CC among different species of Citrus varies from the highly susceptible lime (Citrus × aurantifolia), sweet orange (C. × sinensis), and grapefruit (C. × paradisi) to the much less susceptible calamondin (C. × microcarpa) and kumquat (C. japonica). This investigation compares the responses to infection with X. citri subsp. citri of these five genotypes with respect to phenylpropanoid compound profiles and relative increases or decreases of specific compounds postinoculation. In response to X. citri subsp. citri infection, all hosts possessed increased concentrations of phenylpropanoids in leaf tissue, whereas the similarly treated nonhost orange jessamine (Murraya paniculata) did not. Several of the tested genotypes exhibited notably increased production of fluorescent phenylpropanoids, including umbelliferone, herniarin, auraptene, scoparone, and others. The profiles of these compounds and their levels of production varied among the tested species yet all investigated Citrus genotypes exhibited increased concentrations of phenylpropanoids regardless of their degree of susceptibility to X. citri subsp. citri. Kumquat and calamondin, the tested genotypes least susceptible to X. citri subsp. citri, also exhibited the highest levels of the dihydrochalcone 3',5'-di-C-glucosyl phloretin, the aglycone portion of which, phloretin, is a known antibiotic, although levels of this compound were not affected by inoculation with X. citri subsp. citri.

Effectiveness of Eriomin® in managing hyperglycemia and reversal of prediabetes condition: A double-blind, randomized, controlled study.

This study evaluated the potential effectiveness of different doses of Eriomin® on hyperglycemia and insulin resistance associated with other metabolic biomarkers in prediabetic individuals. Prediabetes patients (n = 103, 49 ± 10 years) were randomly divided into four parallel groups: (a) Placebo; (b) Eriomin 200 mg; (c) Eriomin 400 mg; and (d) Eriomin 800 mg. Assessment of biochemical, metabolic, inflammatory, hepatic, renal, anthropometric markers, blood pressure, and dietary parameters were performed during 12 weeks of intervention. Treatment with all doses of Eriomin (200, 400, and 800 mg) had similar effects and altered significantly the following variables: blood glucose (-5%), insulin resistance (-7%), glucose intolerance (-7%), glycated hemoglobin (-2%), glucagon (-6.5%), C-peptide (-5%), hsCRP (-12%), interleukin-6 (-13%), TNFα (-11%), lipid peroxidation (-17%), systolic blood pressure (-8%), GLP-1 (+15%), adiponectin (+19%), and antioxidant capacity (+6%). Eriomin or placebo did not influence the anthropometric and dietary variables. Short-term intervention with Eriomin, at doses of 200, 400, or 800 mg/day, benefited glycemic control, reduced systemic inflammation and oxidative stress, and reversed the prediabetic condition in 24% of the evaluated patients.

Analysis of Fluorescence Spectra of Citrus Polymethoxylated Flavones and Their Incorporation into Mammalian Cells.

Citrus polymethoxylated flavones (PMFs) influence biochemical cascades in human diseases, yet little is known about how these compounds interact with cells and how these associations influence the actions of these compounds. An innate attribute of PMFs is their ultraviolet-light-induced fluorescence, and the fluorescence spectra of 14 PMFs and 7 PMF metabolites were measured in methanol. These spectra were shown to be strongly influenced by the compounds' hydroxy and methoxy substituents. For a subset of these compounds, the fluorescence spectra were measured when bound to human carcinoma Huh7.5 cells. Emission-wavelength maxima of PMF metabolites with free hydroxyl substituents exhibited 70-80 nm red shifts when bound to the Huh7.5 cells. Notable solvent effects of water were observed for nearly all these compounds, and these influences likely reflect the effects of localized microenvironments on the resonance structures of these compounds when bound to human cells.