Citrus bioflavonoids and sleep quality -
Melatonin 3 mg tablets. Item added to your cart. Check out Continue shopping. No reviews. Learn More. Buy Now. Couldn't load pickup availability Refresh. Melatonin 3 mg tablets Helps you fall asleep faster and stay asleep longer Supports restful sleep and helps regulate your mood Helpful for people with sleep disorders like insomnia Each bottle contains tablets with 3 mg of Melatonin each Other Ingredients: Dicalcium Phosphate, Vegetable Cellulose.
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Derived from citrus fruit peels, Citrus Bioflavonoids is rich in bioflavonoids — the natural pigments that give fruits and vegetables their brilliant color. Bioflavonoids both enhance the absorption and act in synergy with vitamin C to provide antioxidant protection, keep collagen healthy and help increase capillary strength.
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Add to cart. Couldn't load pickup availability Refresh. Loading store locator from Stockist store locator Skip to product information. Key Ingredient Quercetin Quercetin is a natural plant pigment classified as a bioflavonoid. Learn More About Quercetin Find out why this little known substance is the latest addition to your daily health regime.
Learn More. Key Ingredient Turmeric Native to Southeast Asia, the brilliant yellow spice turmeric is a member of the ginger family. What are the Benefits of Turmeric? Key Ingredient Oregano Oregano is no average herb.
What are the Benefits of Oregano? Key Ingredient Licorice Root Before it became a popular culinary ingredient, licorice was used as a medicine by ancient civilizations throughout Europe and Asia.
What are the Benefits of Licorice Root? Key Ingredient Echinacea Echinacea, a popular flowering plant native to North America, is no stranger to health enthusiasts.
What are the Benefits of Echinacea? Key Ingredient Cranberry For many people, these tart North American berries are too lip-puckering to eat fresh. What are the Benefits of Cranberry? Key Ingredient Milk Thistle This Mediterranean herb with spiky purple flowers, named after its milky white veins, has been treasured for its healing properties since the first century AD.
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Key Ingredient Pharma GABA Gamma-aminobutyric acid, also simply known as GABA, has been clinically shown to be effective in helping soothe a racing mind. What is Pharma GABA®? What Else Should I Know? Suggested Usage. Allergy Information. Where can I find this? Find this product from one of our trusted independent natural health retailers.
Bioflavonoids are plant compounds that Immune system support for athletes vitamin-like Bioflavoniods and Citeus superior antioxidant activity. Natural Factors Citrus Bioflavonoids are derived from the rind and pulp of citrus biovlavonoids. Citrus bioflavonoids and sleep quality hesperidin, a bioflavonoid also derived quaity citrus, qyality Citrus bioflavonoids and sleep quality antioxidant activity to help fight the effects of free radicals. Bioflavonoids are a group of plant pigments that are largely responsible for colours of many fruits and vegetables, and include a large number of nutrients with antioxidant activity. They are sometimes referred to as vitamin P because they have vitamin-like properties. Citrus bioflavonoids are derived from the rind and pulp of citrus fruits. Citrus bioflavonoids work synergistically with vitamin C as they are needed for vitamin C to be used effectively by the body.Citrus bioflavonoids and sleep quality -
Table 2. Overview of citrus flavonoids on cognitive performance and locomotor activity in preclinical models. Whilst a wealth of pre-clinical reviewed above and in vitro data exploring neurocognitive outcomes in relation to citrus flavonoids is currently available, the same cannot be said for human trials which remain considerably limited in number.
In our literature search, we identified 10 human studies five observational; five interventions assessing the effects of citrus flavonoids on brain health and cognition in healthy adults, or in addition to other co-morbidities including depression, dementia, schizophrenia, and stroke.
The benefits of citrus fruit consumption in the context of healthy aging were highlighted by a cross-sectional study involving elderly aged 70—74 years Norwegian individuals which explored the impact of different plant foods on cognitive performance Nurk et al.
Study participants underwent extensive cognitive testing in addition to completing comprehensive food frequency questionnaires. After adjustment for multiple testing, citrus fruits had the strongest association with cognitive test performance. Kendrick object learning, trial making, digit symbol and block design tasks all showed statistically significant improvements suggestive of better episodic memory, executive function, perceptual speed, and visuospatial skills Table 3.
Table 3. Overview of intervention studies on citrus fruits in brain health and disease in humans. Following on from these observations, Kean et al. In support of the cross-sectional study mentioned above, global cognition increased in response to chronic consumption of the flavanone-rich orange juice relative to control.
These effects were independent of mood and blood pressure which both remained unchanged Table 3. Acute neurological responses to citrus flavonoids have similarly been investigated Alharbi et al. Firstly, in a randomized, double-blind, placebo-controlled, crossover trial, Alharbi et al. From the cognitive battery performed, flavonoid rich orange juice consumption led to higher performance in Simple Finger Tapping measure of psychomotor speed and Continuous Performance Task measure of attention and more broadly executive function at 2 and 6 h respectively.
A non-significant trend for higher global cognitive performance all tests combined was also observed, as well as an increase in subjective alertness. Interestingly, significant improvements observed in cognition and subjective alertness at 6 h coincide with an anticipated peak in flavanone metabolites at 5—7 h Manach et al.
As with the previous study, Lamport et al. The study was single blind, randomized, cross over, by design involving healthy adult volunteers aged 18—30 years. High flavanone beverage intake significantly increased cerebral perfusion in the inferior frontal and middle right frontal gyrus in the right hemisphere at 2 h.
Similarly, at 2 h, improvement in digit symbol substitution test a measure of executive function was seen, correlating with the increased regional perfusion of the inferior frontal gyrus, known to be involved in executive function Aron et al. Despite the extensive cognitive battery, no additional effects were found.
However, as addressed by the authors, this study had a number of limitations. In particular, the fact MRI and cognitive test were performed on separate individuals, and that cognitive tests were only performed at 2 h limits comparative potential.
Additionally, as stated by the authors, the fact that the participants were generally young and highly educated may have limited the response given they were likely to be optimally functioning Table 3. Depression is a complex mood disorder which can often be challenging to treat effectively.
Preclinical studies have reported anti-depressant effects of flavonoids, usually attributable to their antioxidant and anti-inflammatory characteristics, and inhibition of monoamine oxidases Hritcu et al.
An important serological marker identified in depression is BDNF involved in processes within the central nervous system which has been observed to be significantly lower in patients with major depressive disorder compared to non-depressed control groups, and subsequently recovered antidepressant users Chen et al.
Interestingly, BDNF is often increased in response to flavonoid consumption Neshatdoust et al. These anti-depressant effects of citrus flavonoids were recently put to the test by Park et al. The results in relation to depression were by no means clear cut, with no apparent significant differences between high and low flavonoid groups after 8 weeks.
However, compared with baseline the results suggested potential improvement in BDNF, and to some extent to the Center for Epidemiological Studies Depression Scale CES-D , a psychiatric screening tool used to detect pre-existing mental disorders, although both treatments appeared to improve upon baseline CES-D scores Table 3.
there remains very limited evaluation at the human level. In a retrospective cohort study Zhang et al. FFQs in combination with the Japanese Long-term Care Insurance database were used over a 5. As dementia represents a wide range of neurodegenerative diseases, lack of further classification limits the extent to which we can attribute these effects to specific neurodegenerative diseases and should be considered in future studies Table 3.
Schizophrenia is a complex psychotic condition affecting cognition, the cognitive hallmark of schizophrenia being poor learning and retention of verbal information Bowie and Harvey, With a trend for other cognitive variables evident Bruno et al.
The protective effects of citrus flavonoids in cerebrovascular disease are well documented Testai et al. A prospective cohort study, assessing the association of dietary flavonoid intake toward stroke risk, followed 69, women 30—55 years from the NHS Study throughout a year period Cassidy et al.
These apparently protective effects did not influence haemorrhagic strokes Scheffers et al. A recent prospective cohort study Goetz et al. In agreement with the above-mentioned study of total flavonoids and other flavonoid subclasses did not show any statistically significant association with incident ischemic stroke, clearly showcasing the importance of the flavanone subclass Table 3.
Of particular relevance to the mitigation of stroke risk, and also neurodegenerative conditions, it is worth briefly mentioning the influence of citrus flavonoid intake on blood pressure, and vascular functions. RCTs in which flavonoids were administered in the form of orange juice have established significant reductions in blood pressure Morand et al.
The preclinical literature search distinguished fundamental mechanisms central to citrus flavonoids, with protective effects linked with anti-oxidative and anti-inflammatory action particularly well established. Yet, there are a number of areas requiring further investigation. First, the overwhelming majority of studies to date involve relatively young male animals making it difficult to establish whether or not the observable effects are sex or age specific.
Nor do we have an understanding of modulation by either factor. Second, the models employed tend to lean toward the severe side of the disease spectrum, thus translation to a healthy aging context, or milder conditions, remains to be fully determined, although some initial work provides supportive results Liaquat et al.
From a human perspective, there is an obvious lack of human clinical studies which needs to be addressed if a robust assessment of therapeutic potential is to be made.
Similarly, very few human studies have followed up on the mechanistic insights established in the preclinical setting. Future human studies should take note of the limitations arising from other human studies in which nutraceuticals were assessed in the context of brain health and disease, for example ensuring optimal participant targeting in demographics where significant change is most likely to occur , dosage, timing, and duration of treatment for measurable effects to be established.
The complex mixtures of polyphenols present in citrus fruits and juices and their bioactive nuances likely convey greater benefit than one purified compound, accumulatively acting upon multiple targets, and producing synergistic effects. Given the multifactorial nature of neurodegenerative diseases, one would speculate that this complex form would therefore offer greater efficacy, but this is yet to be fully determined.
In conclusion, although significant work remains to fully establish the benefits of citrus polyphenols in brain health and disease, the accumulating in vitro and preclinical data combined with the support of steadily emerging human studies indicates future potential.
MP, MMM, and DV wrote the manuscript. MP, MMM, EC, MM, and DV contributed to the literature search and edited the manuscript. All the authors contributed to the article and approved the submitted version.
MP and DV received unrestricted honorariums from the Fruit Juice Science Centre. The article reflects the views of the authors alone, and the funding source had no role in the preparation or submission of the manuscript.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Agosta, F. Dementia and neuroimaging. doi: PubMed Abstract CrossRef Full Text Google Scholar.
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Iglesias-Carres, L. Clinical trials in patients with proven sleep disorders indicate that the combination of orange extract with valerian root extract or hop extract is superior to both conventional preparations, ie valerian root extract or hop extract, given in a statistically significant manner.
The best effect was when a combination of three valerian root extract, hops extract and orange extract was administered. The experiments were carried out with the orange extract "Hesperidina Farma" from Exquim S. The valerian extract used was a dry extract "Valeriane extractum hydroalcoholicum siccum Ph.
Der Anteil an Xanthohumol und Isoxanthohumol beträgt mind. Die Veränderungen der EEG-Frequenzen wurde nach Gabe von Salzlösung Kontrolle bzw. Placebo bzw. oral von Orangenextrakt in verschiedenen Kombinationen mit anderen Extrakten bestimmt. The changes in the EEG frequencies were determined after administration of saline solution control or placebo or orally from orange extract in various combinations with other extracts.
Die Untersuchungen wurden analog der durch W. Dimpfel beschriebenen Methode Dimpfel W: Preclinical data base of pharmaco-specific rat EEG fingerprints Tele-Stereo-EEG. Eur J Med Res 8: — folgendermaßen durchgeführt: Sechs männlichen erwachsenen Fischer Ratten Tag-Nacht konvertiert wurden im Alter von 6 Monaten 4 bipolar konzentrische Elektroden zusammen mit einem Mikrostecker auf einer gemeinsamen Basisplatte implantiert.
Der Stecker diente der Aufnahme eines 4-Kanal-Senders zur telemetrischen Übertragung der aus frontalem Kortex, Hippocampus, Striatum und Formatio Reticularis abgeleiteten Feldpotentiale.
Die Unterteilung der Spektren in 6 verschiedene Frequenzbereiche erlaubte die Erfassung pharmako-spezifischer Veränderungen in Bezug auf die jeweils vor Applikation gemessenen Vorwerfe innerhalb dieser Frequenzbänder. The investigations were carried out analogously to the method described by W.
Dimpfel Dimpfel W: Preclinical data base of pharmaco-specific rat EEG fingerprints Tele-Stereo-EEG. Eur J Med Res 8: carried out as follows: Six male adult Fischer rats day-night converted were implanted at the age of 6 months 4 bipolar concentric electrodes together with a micro connector on a common base plate.
The plug was used to record a 4-channel transmitter for telemetric transmission of the field potentials derived from the frontal cortex, hippocampus, striatum and formatio reticularis. The signals were subjected to Fast Fourier Transformation in real time on a computer system "EEG Analysis" software, OS Science operating system, "LabTeam" lab computer from MediSyst, Linden, DE , and the power density spectra were each averaged over 60 minutes.
The subdivision of the spectra into 6 different frequency ranges allowed the detection of pharmaco-specific changes with respect to the pre-embrasures measured before each application within these frequency bands. Zum Applikationsprotokoll der Präparate: die Präparate wurden oral 45 Minuten nach Beginn der Messungen Vorwert appliziert.
Fünf Minuten später wurden die Messungen wieder gestartet, mindestens über die nächsten 5 Stunden kontinuierlich analysiert und in minütigen Perioden zusammengefaßt.
Die Testpräparate wurden in unterschiedlichen Kombinationen appliziert. Die experimentelle Serie wurde mit der Injektion von Salzlösung Kontrolle , die zu keiner auffälligen Änderung führte, begonnen.
The application protocol of the preparations: the preparations were administered orally 45 minutes after the start of the measurements pre-value. Five minutes later, measurements were restarted, continuously analyzed for at least the next 5 hours, and pooled into minute periods.
The test preparations were applied in different combinations. The experimental series was started with the injection of saline control , which did not lead to a noticeable change.
Der statistische Vergleich der Versuche zu den Ergebnissen, die nach Gabe von Salzlösung gemessen wurde, erfolgte nach Wilcoxon, Mann and Whitney auf der Basis der Veränderungen innerhalb der einzelnen Frequenzbänder in allen Hirnregionen als Variablen.
The statistical comparison of the experiments to the results measured after administration of saline solution was made according to Wilcoxon, Mann and Whitney based on the changes within the individual frequency bands in all brain regions as variables.
Bei den Untersuchungen der Veränderungen der EEG-Frequenzen der Ratte wurde aber überraschenderweise im Vergleich zur alleinigen Gabe von Baldrianextrakt oder Hopfenextrakt eine deutlich stärkere Zunahme der theta und beta1 Wellen nach Kombination mit Orangenextrakt gefunden, die bei einer Behandlung von Schlafstörungen nützlich ist, da die Zunahme dieser Frequenzen mit der Schlaftiefe korreliert.
Surprisingly, however, in the studies of changes in EEG frequencies of the rat, a significantly greater increase in the theta and beta1 waves after combination with orange extract, which is useful in the treatment of sleep disorders, was found when compared to the sole administration of valerian extract or hop extract of these frequencies correlates with the depth of sleep.
Die Verabreichung von Orangenextrakt in Kombination mit Baldrianwurzelextrakt oder Hopfenextrakt führte zu stabilen Veränderungen der Leistungsdichte in allen Hirngebieten, vor allem während der dritten bis fünften Stunde nach Applikation siehe.
Administration of orange extract in combination with valerian root extract or hops extract resulted in stable changes in power density in all brain areas, especially during the third to fifth hour after application see.
Die orale Verabreichung von Extraktkombinationen als Einzeldosis führte zu Veränderungen der elektrischen Hirnaktivität bei den Testtieren, die denen während des Schlafes ähnelten. Insbesondere ist dies überraschend, da die Präparate am Morgen, d. nach der Nachtruhe verabreicht wurden.
Oral administration of extract combinations as a single dose resulted in changes in brain electrical activity in test animals similar to those during sleep.
In particular, this is surprising because the preparations in the morning, d. were administered after sleep.
Die zeigt die zeitabhängigen Veränderungen der theta EEG Frequenzen nach oraler Verabreichung verschiedener Dosierungen von Orangenextrakt, Baldrianwurzelextrakt und Hopfenextrakt allein sowie als Dreierkombination.
In früheren Versuchen konnte gezeigt werden, daß vor allem die theta und beta1 Wellen des EEG die Schlaftiefe repräsentieren Dimpfel W, Hofmann H-C Mehrdimensionale Dokumentation des Schlafes auf der Grundlage der Frequenzanalyse. In Mayer G Hrgs. Jahrbuch Schlafmedizin Deutschland MMV Verlag, München.
Obwohl der Orangenextrakt bei alleiniger Gabe keine Erhöhung der theta Frequenzen bewirkt, ist zu erkennen, daß die trotz hoher Dosis ebenfalls nur geringe Wirkung von Baldrianwurzelextrakt oder Hopfenextrakt bei der Einzelapplikation durch die Kombination von Orangenextrakt, Baldrianwurzelextrakt und Hopfenextrakt massiv überboten wird und damit eine größere Schlaftiefe erreicht wird.
Zudem ist in der Kombination nur die halbe Dosis beider klassischen Extrakte vorhanden, was auf eine Potenzierung durch den Orangenextrakt schließen läßt. The shows the time-dependent changes in the theta EEG frequencies after oral administration of various doses of orange extract, valerian root extract and hops extract alone, and as a triplicate combination.
In previous experiments it could be shown, that above all the theta and beta1 waves of the EEG represent the sleep depth Dimpfel W, Hofmann HC Multidimensional documentation of sleep on the basis of the frequency analysis Mayer G Hrgs Yearbook Sleep Medicine Germany MMV Verlag, Munich , Although the orange extract when administered alone does not cause an increase in the theta frequencies, it can be seen that, in spite of the high dose, the valerian root extract also has only a slight effect or hop extract in the single application by the combination of orange extract, valerian root extract and hops extract massively outbid and thus a greater sleep depth is achieved.
In addition, in the combination only half the dose of both classic extracts is present, which suggests a potentiation by the orange extract. Ähnliches trifft für die für die Schlaftiefe wichtige beta1 Frequenz zu.
Wie in dargestellt übertrifft die Wirkung der Kombination die Wirkung beider Einzelextrakte deutlich, wobei Orangenextrakt allein keine Wirkung erkennen läßt. The same applies to the sleep depth important beta1 frequency. As in the effect of the combination clearly exceeds the effect of both single extracts, with orange extract alone showing no effect.
Diese Wirkung konnte bei Schlaf-gestörten Patienten bestätigt werden. Nachdem der auf der Basis der theta und beta Frequenzen definierte spektrale Frequenzindex Apparatus for determining sleep staging: US Pat.
Zweierkombinationen mit Orangenextrakt während einer Nacht bestimmt worden war, ergab sich eine erheblich größere Schlaftiefe für die Dreierkombination im Vergleich zu beiden Zweierkombinationen Es wurden immer dieselben Patienten im Abstand von mehreren Tagen untersucht.
Das Ergebnis der Studie ist in dokumentiert. This effect was confirmed in sleep-disordered patients. After the spectral index of frequencies defined on the basis of the theta and beta frequencies Apparatus for determining sleep staging: US Pat.
The result of the study is in documented. Betrachtet man darüber hinaus, wie viel Zeit die Patienten innerhalb einer jeweils bestimmten Schlaftiefe verbracht haben, ergibt sich eine klare Überlegenheit der Dreierkombination im Vergleich zu Placebo.
Dies ist in dokumentiert. Gleichzeitig ist ersichtlich, wie die Wirkung der Dreierkombination sich dem gesunden Schlaf nähert. Aus der Erkenntnis, das Orangenextrakt die für Schlaftiefe repräsentativen Parameter signifikant beeinflußt, muß geschlossen werden, daß der Zusatz von Orangenextrakt den Schlaf von Patienten deutlich bessert, was bislang unbekannt und auch nicht zu vermuten war.
In addition, considering how much time the patients spent within each particular sleep depth, the triple combination is clearly superior to placebo. This is in documented. At the same time it can be seen how the effect of the triple combination approaches healthy sleep.
From the finding that orange extract significantly affects the parameters representative of sleep depth, it must be concluded that the addition of orange extract significantly improves the sleep of patients, which was previously unknown and could not be assumed. Die bereits anhand einer früheren Studie publizierte Korrelation Dimpfel W, Hoffmann H-C, Schober F, Todorova A Validation of an EEG-derived spectral frequency index SFx for continuous monitoring of sleep depth in humans.
Eur J Med Res ; 3: — konnte auch in dieser Studie wieder belegt werden, wie in erkennbar ist. Daher muß auf Grund dieser Ergebnisse angenommen werden, daß eine Kombination pflanzlicher Schlafmittel mit Orangenextrakt zu einem hochpotenten Naturheilmittel zur Behandlung von Schlafstörungen mit geringem Nebenwirkungspotential führen wird.
The validity of the "spectral frequency index" SFx surrogate parameter evaluated and patented using the EEG record is also substantiated by the correlation analysis between the change in the SFx and the subjective quality of sleep recorded in a questionnaire.
The correlation already published on the basis of an earlier study Dimpfel W, Hoffmann HC, Schober F, Todorova A Validation of an EEG-derived spectral frequency index SFx for continuous monitoring of sleep depth in humans.
Eur J Med Res ; 3: was again demonstrated in this study, as in is recognizable. Therefore, based on these results, it must be assumed that a combination of herbal sleeping tablets with orange extract will result in a highly potent natural remedy for the treatment of sleep disorders with low side effect potential.
Eur J Med Res ; 3: — Dieser neue Parameter, als spektraler Frequenzindex SFx bezeichnet, erfaßt die Schlaftiefe kontinuierlich und somit auch die gleitenden Übergänge der ca. Dadurch werden u. auch alle Aufwachvorgänge, die bekanntlich zu wenig erholsamen Schlaf führen, automatisch mit erfaßt und ausgewertet.
Eur J Med Res ; 3: This new parameter, referred to as the spectral frequency index SFx , continuously records the depth of sleep and thus also the sliding transitions of the individual sleep phases lasting about 90 minutes.
As a result, among other things, all wake-up procedures, which are known to lead to less restful sleep, automatically detected and evaluated.
A double blind, randomized, placebo-controlled sleep-EEG study in a parallel design using the electrohypnogram. Eur J Med Res ; — Eur J Med Res ; Die vorgenannten Beispiele dienen der Erläuterung der Erfindung, ohne daß die Erfindung jedoch auf die speziell beschriebenen Ausführungsformen beschränkt sein soll.
The above examples serve to illustrate the invention, but without the invention being limited to the specifically described embodiments.
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Zitierte Patentliteratur Cited patent literature. Zitierte Nicht-Patentliteratur Cited non-patent literature. Effective date : Der IUAPC-Name von Hesperidin ist 2S 6-O- 6-Desoxy-α-L-mannopyranosyl -β-D-glucopyranosyl oxy -2,3-dihydrohydroxy 3-hydroxymethoxyphenyl -4Hbenzopyranon CAS-Nummer entsprechend der Summenformel C 28 H 34 O 15 und der allgemeinen Strukturformel:.
Wirkstoffkombinationen nach Anspruch 1, dadurch gekennzeichnet, daß sie Hesperidin in Form eines Pflanzenextrakts, bevorzugt eines Zitrusfruchtextrakts, insbesondere in Form von Orangenextrakt enthalten. Active substance combinations according to Claim 1, characterized in that they contain hesperidin in the form of a plant extract, preferably a citrus fruit extract, in particular in the form of orange extract.
Wirkstoffkombinationen nach Anspruch 3, dadurch gekennzeichnet, daß der pflanzliche Wirkstoff in Form eines Pflanzenextrakts eingesetzt wird. Active substance combinations according to Claim 3, characterized in that the herbal active ingredient is used in the form of a plant extract.
Schlafmittel oder Nahrungsergänzungsmittel nach Anspruch 5, dadurch gekennzeichnet, daß sie Hesperidin in Form eines Pflanzenextrakts, bevorzugt eines Zitrusfruchtextrakts, insbesondere in Form von Orangenextrakt enthalten. Sleep aid or dietary supplement according to claim 5, characterized in that it contains hesperidin in the form of a plant extract, preferably a citrus fruit extract, in particular in the form of orange extract.
Kombination nach Anspruch 9, dadurch gekennzeichnet, daß sie von bis mg Orangenextrakt, insbesondere von bis mg enthält. Combination according to claim 9, characterized in that it contains from to mg of orange extract, in particular from to mg. Kombination nach Anspruch 9 oder 10, dadurch gekennzeichnet, daß sie von 50 bis mg Hopfenextrakt, insbesondere von bis mg enthält.
Combination according to claim 9 or 10, characterized in that it contains from 50 to mg hops extract, in particular from to mg.
Kombination nach einem der Ansprüche 9—11, dadurch gekennzeichnet, daß sie von bis mg Baldrianwurzelextrakt, insbesondere von bis mg enthält. Combination according to any one of Claims , characterized in that it contains from to mg valerian root extract, in particular from to mg.
Schlafmittel oder Nahrungsergänzungsmittel nach einem der Ansprüche 5—7 oder 13, dadurch gekennzeichnet, daß sie zur oralen Verabreichung hergerichtet sind. Sleep aid or dietary supplement according to any one of claims or 13, characterized in that they are prepared for oral administration.
DEA DEA1 en. EPA EPA1 en. DEA1 true DEA1 en. DEA Ceased DEA1 en. EPA1 en. melanogaster model. The midgut of D. melanogaster is well comparable with the mammalian small intestine 24 , 25 , 26 , 27 making the fruit fly a valuable model organism for studying the effects of bioactive compounds on the intestinal barrier.
We also investigated the antioxidant properties of glycosylated flavanones and their aglycones in the fruit fly, as D. melanogaster is a well-established model in oxidative stress research 28 , 29 , Taken together, we demonstrated an efficient method of flavanone biotransformation via a combination of acid hydrolysis and 24 h-fermentation and provided a comprehensive approach to study the bioactivity of these biotransformed flavanones.
Superior antioxidant and anti-inflammatory activities were observed for biotransformed citrus extracts with increased hesperetin and naringenin content. First, we confirmed the degradation process described in Fig.
Our results indicated that α-L-rhamnosidase from prokaryotic source was able to hydrolyze the rutinosides narirutin and hesperidin, in which L-rhamnose is α-1,6-linked to β-D-glucoside, but did not cleave the neohesperidosides naringin and neohesperidin, in which L-rhamnose is α-1,2-linked to β-D-glucoside Supplementary Figure 1a.
In contrast, β-D-glucosidase increased naringenin and hesperetin by degradation of naringenin O -glucoside and hesperetin O -glucoside, respectively Supplementary Figure 1b.
Next, we screened four different LAB strains, namely L. plantarum DSM , Lacticaseibacillus rhamnosus NCTC L. rhamnosus , Levilactobacillus brevis DSM L.
brevis and Lacticaseibacillus paracasei DSM L. paracasei , to determine whether they produce the enzymes required for increasing the aglycone levels in AQE. The specific LAB strains were selected based on literature research 16 , 17 , 31 and their safety for use in food and feed.
Although flavonoids have a low water solubility, water was used as solvent for citrus extract preparation because other organic solvents such as ethanol would have greatly inhibited bacterial growth during fermentation.
After fermentation, the citrus extracts were centrifuged to remove the bacteria from the extract. Thus, the stated concentrations refer to flavonoids dissolved in the supernatant.
All tested bacteria were able to convert naringenin O -glucoside and hesperetin O -glucoside into the aglycones naringenin and hesperetin, respectively. These findings led us to the assumption that all strains have β-glucosidase activity but no noticeable α-rhamnosidase activity.
Thus, medium without glucose was used for fermentation of extracts. Next, we enhanced the efficiency of glycolytic cleavage by adding acid hydrolysis.
First, the L-rhamnose group was split off from naringin, neohesperidin, hesperidin and narirutin using citric acid, resulting in citric acid hydrolyzed extract CAE. In a next step, the resulting 7- O -glucosides, namely naringenin O -glucoside and hesperetin O -glucosides, were converted to aglycones by the bacterial β-glucosidase activity.
As presented in Fig. Thus, this strain was used for preparation of the final extracts Fig. As shown in Supplementary Figure 4 , co-cultivation of L. plantarum with different LAB strains did not improve the aglycone yield significantly.
a Representative images of L. plantarum, L. rhamnosus, L. brevis and L. paracasei showing gram-positive rods. Control refers to the sample without bacteria.
a Schematic diagram of extract preparation. Aqueous extract AQE was prepared with water instead of citric acid. For fermentation, AQE and CAE were incubated with L. Control extracts were diluted in modified MRS and incubated without bacteria referred to as AQE and CAE.
b Influence of hydrolysis with increasing citric acid CA concentrations 0. c Increase in aglycones after 24 h-incubation with L. d Flavonoid concentrations in the final extracts prepared with water AQE and FermAQE or 0.
Next, we performed acid hydrolysis with different citric acid concentrations to optimize the deglycosylation process. We first aimed to increase the content of 7- O -glucosides by acid hydrolysis so that they could be converted to aglycones by bacterial β-glucosidase activity.
The higher the acid concentration, the more efficient the hydrolysis of naringin to naringenin O -glucoside as well as neohesperidin to hesperetin O -glucoside was. Subsequent fermentation by L. plantarum significantly reduced these 7- O -glucosides to aglycones Fig. The increase of naringenin and hesperetin was significantly higher in fermented extract that was previously treated with 0.
Contrary to expectations, higher initial 7- O -glucoside levels due to higher citric acid concentrations 0. Thus, we used the lowest citric acid concentration 0. Flavanone profiles of the four final extracts AQE, FermAQE, CAE and FermCAE that were used for in vitro and in vivo experiments are provided in Fig.
As mentioned above, only dissolved flavonoids in the supernatant after centrifugation were considered for our final extracts. However, the entire fermentation product also includes precipitated flavonoids in the residue. We could show that the percentage of flavonoids in the pellet was low, with a maximum of 2.
Of these, aglycones accounted for the largest proportion with 0. Supplementary Figure 6 summarizes the proportions of flavonoids in supernatant and pellet for all extracts. Taken together, the combination of citric acid hydrolysis and fermentation with L. plantarum was proven to be the most effective method to transform glycosides into aglycones in the citrus extract.
To demonstrate, whether the amount of aglycones present in biotransformed citrus extracts is bioavailable to intestinal epithelial cells, we investigated the cellular uptake and transport of flavanones from AQE and FermCAE in differentiated Caco-2 cells.
For uptake tests, the cells were incubated with AQE or FermCAE 2. First, we could prove that cellular uptake of the aglycones naringenin and hesperetin was significantly better than uptake of glycosylated flavonoids in both AQE and FermCAE Fig. Moreover, when cells received higher concentrations of hesperetin and naringenin in form of FermCAE Fig.
a Schematic overview of uptake test 1 or transport test 2 in differentiated Caco-2 cells. Uptake of detectable flavonoids from c aqueous citrus extract AQE and d fermented citric acid hydrolyzed citrus extract FermCAE in Caco-2 cells, normalized to cell protein content.
e TEER values of Caco-2 monolayers before and during transport studies. Transport rate of detectable flavonoids from AQE g and FermCAE h across a Caco-2 monolayer. For transport tests, Caco-2 monolayers were incubated with AQE or FermCAE 2.
The monolayer integrity was controlled by transepithelial electrical resistance TEER measurements. More importantly, we showed that this remains true when flavonoids were applied as a mixture in form of the citrus extracts AQE and FermCAE Fig.
Our findings showed that citric acid hydrolysis and fermentation of citrus extract did not change the dynamics of cellular uptake or hinder cellular transport. On the contrary, we demonstrated that epithelial cells could take up and transport higher absolute amounts of flavonoids without reaching saturation within the concentrations in FermCAE.
Taken together, higher flavonoid contents, provided by biotransformed citrus extract, resulted in a significantly higher uptake and transport creating conditions for superior bioactivity of FermCAE.
The influence of individual flavanones naringin, naringenin, hesperidin and hesperetin and the four citrus extracts of different biotransformation level AQE, FermAQE, CAE and FermCAE on cell viability and intracellular reactive oxygen species ROS formation was investigated in Caco-2 and IPEC-J2 cells.
For ROS measurements, Caco-2 and IPEC-J2 cells were first treated with the phytochemicals and then with suitable stressors, respectively. We compared antioxidant effects of glycosylated flavanones naringin and hesperidin with their respective aglycones naringenin and hesperetin when applied at the same concentration flavonoid stocks prepared in dimethyl sulfoxide, DMSO.
Both aglycones, naringenin and hesperetin, exhibited a significantly stronger reduction of ROS formation in stressed Caco-2 cells than their glycosylated forms naringin and hesperidin Fig. Along with this, the biotransformed extract with the highest aglycone content, FermCAE at a concentration of 2.
Similar findings were obtained for stressed IPEC-J2 cells. In addition, FermCAE at a concentration of 2. Samples containing only bacteria FermBlank or citric acid solution CA Blank without flavanones did not reduce ROS formation in stressed intestinal epithelial cells.
This finding suggests that the superior effect of FermCAE over other citrus extracts was due to its higher aglycone content.
AQE stands for aqueous citrus extract, CAE for citric acid hydrolyzed citrus extract, FermAQE for fermented aqueous citrus extract, FermCAE for fermented citric acid hydrolyzed citrus extract.
Percentage of intracellular ROS accumulation in swine epithelial IPEC-J2 cells after treatment with pure flavanones c or citrus extracts d and subsequent stress induction by tert-butylhydroperoxide tBHP , normalized to stressor treatment.
Control refers to untreated cells; quercetin was used as antioxidant positive control. The wounded area is highlighted in yellow ocher.
Since high ROS levels are associated with impaired wound healing 32 , we next investigated whether the extracts could also improve cell migration and thereby potentially wound healing capacity of IPEC-J2 cells, using a scratch assay.
For this purpose, cells were pre-treated with 1. To compare cell migration between treatments, the cell front velocity, defined as the speed at which cells move toward each other, was calculated. In contrast, all citrus extracts restored cell migration ability, as evident by a significant rise in cell front velocities compared to stressor treatment.
The best effect was observed with FermCAE, which increased cell front velocity by 2. In comparison, the effect of AQE was lower, showing an increase in cell front velocity by 1. To summarize, these data indicate that the increase of naringenin and hesperetin in biotransformed citrus extracts leads to an enhanced reduction of oxidative stress and improved cell migration compared to the respective non-biotransformed extracts.
To study the influence of investigated extracts on inflammatory processes, we first performed a semi-quantitative cytokine array analysis. The concentrations were selected based on cytotoxicity testing Supplementary Figure 7. Membranes pre-loaded with antibodies specific for human cytokines were incubated with the supernatants of treated THP-1 cells.
Captured analytes were then visualized as spots Fig. Spot intensities of important cytokines that were upregulated upon LPS stimulation compared to control are presented in Fig. Both extracts, AQE and FermCAE, reduced the concentrations of insulin-like growth factor-binding protein 3 IGFBP-3 , interleukin 6 IL-6 , interleukin 17A ILA , C-X-C motif chemokine ligand 11 CXCL11 , CC-chemokine ligand 2 CCL2 , CC-chemokine ligand 7 CCL7 , C-X-C motif chemokine ligand 9 CXCL9 , CC-chemokine ligand 20 CCL20 , osteopontin, regulated upon activation, normal T-cell expressed and presumably secreted RANTES and tumor necrosis factor α TNF-α.
The previously most promising extract FermCAE caused stronger reduction of these cytokines than the non-biotransformed extract AQE. Three cytokines, epithelial neutrophil-activating protein 78 ENA or CXCL5 , granulocyte macrophage-colony stimulating factor GM-CSF and vascular endothelial-derived growth factor VEGF , were upregulated by treatment with both extracts but not with LPS alone.
Additional data of cytokine array analysis with the aglycone naringenin are provided in Supplementary Figure 8 , showing a similar cytokine profile to the one with the extracts. a Representative images of cytokine arrays incubated with supernatants of differentiated THP-1 macrophages treated with aqueous citrus extract AQE or fermented citric acid hydrolyzed citrus extract FermCAE under lipopolysaccharide LPS challenge.
Cytokines expressed are presented as duplicate spots. Important cytokines are outlined and marked with numbers. The corresponding spot intensities stated as arbitrary units, A. of these analytes are presented in b. Data of technical duplicates are shown.
c Heat map of cytokines with mean spot intensities in a color range from white low level to blue high level. Based on our findings, we selected five cytokines for further investigation via bead-based multiplex immunoassay Fig.
As expected, LPS significantly upregulated the secretion of these cytokines compared to unstimulated control. Distinctively, the anti-inflammatory effects of the aglycones naringenin and hesperetin were more pronounced than of their glycosylated forms.
Consistent with these data, flavonoid-rich extracts also strongly decreased IL-6, CXCL11, CCL7, CXCL9 and TNF-α Fig. Furthermore, the extract with the highest aglycone content, FermCAE, reduced pro-inflammatory cytokines more efficiently than the other extracts.
a Schematic graph of lipopolysaccharide LPS challenge of THP-1 cells 1 with subsequent multiplex bead-based cytokine immunoassay 2. In conclusion, the results of our in vitro experiments revealed that the aglycones naringenin and hesperetin have a higher bioactivity than respective glycosylated flavonoids found in citrus extracts.
Accordingly, the increase of the aglycone concentration in citrus extracts improved their anti-inflammatory properties. Based on the in vitro experimental results, we further investigated antioxidant and intestinal barrier protective properties of AQE and its corresponding biotransformed extract FermCAE in female D.
Considering the metabolic complexity of the whole organism compared to the cell culture, the effect of food matrix on bioavailability 33 , 34 and the involvement of gut microbiota of D.
melanogaster in intestinal function 35 , 36 , we doubled the treatment extract concentrations compared to the in vitro experiments. The dextran sulphate sodium DSS induced intestinal barrier challenge was performed simultaneously with AQE or FermCAE treatment Fig. DSS-induced rupture of intestinal barrier led to leakage of the blue dye through the entire fruit fly, turning them into so called Smurfs Fig.
The choice of the fruit fly sex was based on the technical aspect of the experiment, such as clear visual identification of Smurfs, and was not due to the expectation of sex-specific effects.
We scored and compared the mortality and visible midgut leakage Smurf phenotype separately, because some DSS-fed flies were not demonstrating Smurf phenotype Fig.
Our findings confirmed, that DSS significantly increases mortality and induces intestinal barrier rupture compared to control fruit flies. Importantly, we observed a significant decrease of mortality in D. melanogaster supplemented with higher concentrations of both citrus extracts Fig.
Visible damage of intestinal barrier was reduced for fruit flies treated with both extracts in a concentration-dependent manner Fig. a Schematic overview of in vivo challenges: 1 dextran sulphate sodium DSS challenge to reduce intestinal barrier integrity; 2 ferrous iron induced oxidative stress in female w D.
melanogaster fed with blue dye 1 with DSS-challenged intestinal barrier Smurf phenotype and 2 in control group. c , d Mortality and Smurf phenotype observed in D.
melanogaster challenged by DSS and treated with citrus extracts for 7 d. e , f Reactive oxygen species ROS level and metabolic activity of D.
RFU stands for relative fluorescence units. g , h Mortality and climbing performance of D. melanogaster stressed with ferrous iron and treated with citrus extracts for 7 d. Taken together, the aglycone-enriched biotransformed citrus extract demonstrated a significant protective effect in female D.
melanogaster under induced intestinal barrier challenge and reduced mortality in stressed fruit flies. To test whether the observed antioxidant effect of biotransformed extracts in vitro could be transferred to an in vivo model, we induced oxidative stress in female D.
In consistency with our in vitro results, citrus extracts significantly reduced ROS in fruit flies in a concentration-dependent manner Fig. Both concentrations of FermCAE also showed a trend towards better antioxidant activity compared to respective concentrations of AQE, with a significant difference between the 2.
No significant improvement of suppressed metabolic activity was observed in any of the stressed and extract-treated flies Fig. All groups with ferrous iron diet demonstrated nearly equal levels of metabolic activity reduction.
In parallel to biochemical parameters, we investigated climbing activity and mortality of D. melanogaster due to oxidative stress. Our findings revealed that FermCAE significantly reduced mortality in flies upon oxidative stress Fig.
This weak positive effect of AQE completely faded when the fitness level of D. melanogaster was concerned. In conclusion, biotransformed extract with highest aglycone content showed a significant antioxidant effect upon induced oxidative stress in female D.
melanogaster , while the protective effect of non-biotransformed extract was weak to absent. In this study, we demonstrated that combination of acid hydrolysis and fermentation with the probiotic bacterium L. plantarum improves the cellular bioavailability and bioactivity of food grade citrus extract due to deglycosylation of its prototypic flavonoids, making this plant material well applicable in nutraceuticals, food supplements or functional food and feed.
Providing mechanistic detail and quantification, we demonstrated the superior antioxidant activity of biotransformed citrus extract in two mammalian intestinal epithelial cell lines, IPEC-J2 and Caco-2, compared to non-biotransformed citrus extracts. Moreover, we were able to show that improvement of bioactivity by biotransformation was attributed to the increase in naringenin and hesperetin levels, which were better taken up by cells than glycosylated flavonoids.
Our findings are consistent with literature on flavonoid uptake in Caco-2 cells, where uptake of naringin normalized to cell protein was previously found to be low In contrast, uptake of its aglycone naringenin was comparatively higher, as confirmed in other studies 40 , Similarly, the transport rate of the aglycone hesperetin was also found to be superior than that of the glycoside hesperidin However, none of the aforementioned studies investigated the cellular uptake and transport of target flavonoids in a mixture within a matrix of a plant extract, in which compounds other than naringin, hesperidin and the respective aglycones were present.
Noteworthy, the extracts were dissolved in HBSS for uptake and transport studies, although HBSS does not mimic the properties and composition of gastrointestinal fluids. Due to technical limitations in HPLC analysis, it was not possible to use a solvent that better simulated intestinal fluids.
The necessary purification steps for removing the interfering compounds would have resulted in analyte concentrations below the detection limit. Considering the connection between oxidative stress and inhibition of wound healing, we could also confirm enhanced cell migration and thus wound healing capacity of IPEC-J2 cells incubated with biotransformed citrus extracts.
No studies were found on naringin, hesperidin and their respective aglycones in the context of our IPEC-J2 experiments. Moreover, the superior bioactivity of fermented citrus extract over non-fermented was confirmed in D. Previous studies indicated antioxidant activities of naringin 43 , 44 and hesperidin 37 , 45 in fruit flies.
In particular, the survival as well as climbing performance of D. melanogaster stressed by iron excess and treated with purified hesperidin was improved 37 , 45 , which is also confirmed with our results despite the slight differences in treatment duration and the way of hesperidin supplementation.
The simultaneous treatment with a different oxidative stressor — trichloroethylene — and hesperidin also significantly reduced the ROS level and restored acetylcholinesterase activity in the fruit flies compared to the stressor only group 37 , The antioxidant effects of the glycoside naringin were as well examined with a different stressor, such as paraquat, and resulted in improved survival rate, as well as locomotor activity 43 , In contrast, the aglycones naringenin and hesperetin or plant extracts containing them have not been investigated in D.
melanogaster so far. Here, we demonstrated an enhanced antioxidant capacity of biotransformed citrus extract with increased concentration of the respective aglycones fed to D. Fermented citrus extract not only reduced ROS level in chemically stressed fruit flies significantly stronger compared to non-biotransformed extract, but also led to superior reduction of stress-induced mortality.
In consensus with our in vitro cell migration experiments in intestinal epithelial cells, intestinal barrier challenge induced by DSS confirmed protective properties of biotransformed citrus extracts in vivo. DSS was proven to induce intestinal tissue damage in D. melanogaster 46 , but remains an underrated instrument to study the protective capacity of phytochemical compounds.
It was previously shown that DSS-induced intestinal inflammation could be reduced by anthocyanins Another study showed that the aglycone hesperetin ameliorated DSS-induced damage in Caco-2 cells, as well as reduces the damage in mice In the present study, we demonstrated that DSS-induced intestinal barrier damage and related mortality in D.
melanogaster were as well reduced due to supplementation of flavonoids in form of citrus extracts hesperetin and naringenin included and this reduction was even greater when aglycone-enriched extracts were applied.
It is important to mention that gut microbiota of living organisms can have an effect on flavonoid bioavailability. Therefore, in the conducted experiments, the intestinal bacteria of D. melanogaster might have influenced the intestinal deglycosylation or further metabolization of naringin and hesperidin in the fed extracts as well.
In the respective in vitro THP-1 model of inflammation, a significantly stronger reduction of pro-inflammatory cytokines could also be traced back to aglycones with naringenin expressing the maximal anti-inflammatory effect.
Our findings on reduction of IL-6 and TNF-α are in line with previously investigated anti-inflammatory properties of naringenin 49 and hesperetin 50 , 51 and expands these data with the anti-inflammatory properties of the biotransformed citrus extracts that contain both aglycones.
To our knowledge, we first demonstrated flavanone-related decreases of the chemokines CXCL11, CCL7, and CXCL9 in the LPS-stimulated macrophage model. In particular, we showed the superior anti-inflammatory properties of naringenin and hesperetin compared to their glycosylated forms naringin and hesperidin, respectively.
Reduction of CCL7 upon naringenin treatment was once demonstrated in high-fat diet-induced obese mice 52 , while CXCL9 and CXCL11 were not investigated in context of flavanones at all.
The topic whether aglycones are more beneficial in the human body than glycosylated citrus flavonoids has been discussed extensively in literature, and to our knowledge, there is still no clear answer.
For example, it has been reported that O -glycosylation of naringenin and hesperetin generally reduces the biological activity, such as anti-inflammatory and antioxidant properties of the compounds but can enhance other biological benefits such as anti-HIV activity, tyrosinase inhibition or anti-rotavirus activity At this point it has to be emphasized that findings from in vitro and in vivo studies are not directly applicable to humans without further investigations.
Therefore, it can neither be generalized that aglycones always have a better effect on human health nor that conversion to aglycones is required to achieve a beneficial effect on health. Given the demonstrated bioactivity of the aglycones naringenin and hesperetin, the question arises whether existing methods of flavonoid deglycosylation, such as enzymatic cleavage, acid treatment or application of genetically modified organisms, are optimal in terms of application field, sustainability and costs.
It was recently demonstrated that incubation with 0. However, application of hydrogen chloride is limited in food and feed technology, unlike citric acid 54 applied in this study. Moreover, citric acid is considered more environmentally friendly than hydrogen chloride because it is metabolized to carbon dioxide and water.
In our approach, a 4. plantarum compared to the citrus extract prepared with water. There have been previous attempts to use citric acid for deglycosylation of flavonoids The researchers increased the extraction yield of the aglycones apigenin and luteolin in celery extract by citric acid hydrolysis and treatment with the purified enzyme β-glucosidase.
They could even increase the content of the aglycones luteolin and apigenin by a factor of However, the biotechnological application of purified enzymes is associated with high costs, since enzyme production is energy- and labor-intensive 56 , and free enzymes cannot be conveniently reused.
In this regard, immobilized enzymes offer the advantage that they can be reused for multiple runs. While highly efficient, enzymatic cleavage, as well as application of bioengineered microorganisms also imply application limitations 58 and heavier environmental footprint.
In our study, we presented a combination of citric acid hydrolysis with tailored LAB fermentation for conversion of glycosylated flavanones to aglycones in food grade citrus extracts.
When material costs are considered, our suggested method is a cost-efficient alternative to the enzymatic deglycosylation and a sustainable technology that assists deglycosylation of flavanones.
For instance, costs of citric acid, LAB strains and nutrient media for initial LAB cultivation, required for biotransformation of one unit of food grade citrus extract, are lower compared to the costs for pure naringinase, required for deglycosylation of the same weight unit, even if the enzyme will be reused multiple times.
Moreover, food-grade components allow the biotransformed plant products to be used as dietary supplements, functional food and beverages, as well as additives for animal feed. Therefore, it might be of interest to use the entire fermentation product including dissolved and undissolved flavonoids as well as bacteria for large-scale applications.
In this study, however, we only used the supernatant with dissolved flavonoids as final extracts for in vitro and in vivo experiments.
Nevertheless, we consider our biotransformation approach a promising method to improve the bioavailability and bioactivity of plant extracts rich in flavanones.
Citrus bioflavonoids complex 60 T named complex 60 was purchased from Evesa Extractos Vegetales S. A Cadiz, Spain. Complex 60, a light brown powder, consists of whole dried fruit of Citrus aurantium var.
amara L. Only the supernatant was used for further experiments. After incubation, sodium citrate solution 0. The final citric acid hydrolyzed extract referred to as CAE was prepared with 0.
plantarum DSM , L. brevis DSM and L. paracasei DSM were obtained from the German Collection of Microorganisms and Cell Cultures GmbH Braunschweig, Germany , while L. rhamnosus NCTC was purchased from the National Collection of Type Cultures NCTC, Salisbury, UK. Modified MRS pH 6. Cells were observed via light microscopy Nikon Eclipse 80i, objective Plan Fluor × 1.
Photos were taken with the Nikon DS U1 camera 5 MPx using the NIS-Elements software Version 5. The pH value of the mixture of medium and extract was approximately 5.
Bioflavoonids you for visiting nature. You iCtrus using a browser version with limited support Citrus bioflavonoids and sleep quality CSS. Bifolavonoids obtain the best experience, Energy boosting herbs recommend you Citrus bioflavonoids and sleep quality a more Herbal weight loss aids to date browser or bioflavooids off compatibility mode Natural anti-aging supplements Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Many bioactive plant compounds, known as phytochemicals, have the potential to improve health. Unfortunately, the bioavailability and bioactivity of phytochemicals such as polyphenolic flavonoids are reduced due to conjugation with sugar moieties. Here, we combine acid hydrolysis and tailored fermentation by lactic acid bacteria Lactiplantibacillus plantarum to convert the biologically less active flavonoid glycosides hesperidin and naringin into the more active aglycones hesperetin and naringenin. In addition slefp essential micronutrients such Natural anti-aging supplements sleel C, citrus Diuretic effect on urinary frequency bikflavonoids a considerably rich source of non-essential bioactive bioflavonoods, in particular flavanones which quslity a Natural detox for fighting free radicals of the flavonoid Citruus. Encouragingly, results from human studies, although limited in number, appear to support this preclinical basis, with improvements in cognitive performance and disease risk observed across healthy and disease states. In addition, there should be further exploration of citrus polyphenols to establish therapeutic efficacy, particularly in the context of well-designed human interventions. A varied and balanced diet, rich in plant-derived material fruit and vegetablesis widely regarded as optimal for maintaining overall health and wellbeing. Unfortunately, typical modern dietary preferences are increasingly skewed in favor of nutrient poor, calorie dense, ultra-processed food choices.
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