Route of administration determines the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin — are they prodrugs?

Vissiennon, C; Nieber, K; Kelber, O; Butterweck, Veronika

doi:10.1016/j.jnutbio.2011.03.017

Cited by 132 publications

(99 citation statements)

References 43 publications

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“…Adolf Nahrstedt on the occasion of his 75th birthday for his achievements in SJW research. otic treatment, the anxiolytic effect of kaempferol and quercetin disappeared, whereas it was still present for the positive control diazepam [34]. Results support the hypothesis that the flavonoids are not only absorbed as aglyca, as is known from pharmacokinetic studies [35,36], but also as their hydroxyphenylacetic acid metabolites, and act therefore also as prodrugs.…”

Section: Dedicationsupporting

confidence: 75%

The mechanisms of action of St. John’s wort: an update

Schmidt¹,

Butterweck

2015

Wien Med Wochenschr

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Pharmacological research confirms and supports the clinically observed antidepressant efficacy of St. John's wort (Hypericum perforatum L., SJW). This contribution is an update of a former review by the authors in 2007. Positive evidence of antidepressant effects has been found with SJW preparations, extract fractions, and single constituents. The efficacy of SJW is obviously defined by a range of parallel mechanisms of action, triggered by different constituents. In vitro research showed, among other tests, positive effects in neurotransmitter regulation (in beta adrenergic systems and glutamate receptors) and ion channel conductance. Antidepressant effects were confirmed in typical in vivo models such as the forced swimming test, the open field test, the tail suspension test, or a model of stress-impaired memory. The overall effect cannot be attributed to a single constituent or fraction. SJW is therefore an outstanding example of the total extract being defined as the active constituent of herbal medicines.

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Section: Dedicationsupporting

confidence: 75%

The mechanisms of action of St. John’s wort: an update

Schmidt¹,

Butterweck

2015

Wien Med Wochenschr

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“…Some healthrelated benefits are associated with this group of compounds, including strengthening of the immune system, protecting against cancer, and reducing capillary fragility (Lu et al, 2013). Because many flavonoid glycosides exhibit low oral bioavailability due to the microbial hydrolysis and conjugation that occurs in the intestine and the liver, this type of compound is generally considered a natural prodrug (Arroo et al, 2008(Arroo et al, , 2009; the health benefits are attributed to the metabolites capable of reaching the circulation (Dorjgochoo et al, 2012;Vissiennon et al, 2012;Romano et al, 2013). However, there have been few biologic/pharmacologic evaluations of the resultant conjugates (Terao, 1999;Koga and Meydani, 2001) because of limited access to the pure compounds.…”

Section: Introductionmentioning

confidence: 99%

The Presystemic Interplay between Gut Microbiota and Orally Administered Calycosin-7-O-β-d-Glucoside

Ruan

et al. 2015

Drug Metab Dispos

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Presystemic interactions with gut microbiota might play important roles in the holistic action of herbal medicines in their traditional oral applications. However, research interests usually focus on biologic activities of the in vivo available herb-derived components and their exposure in circulation. In this study, we illustrated the importance of studying the presystemic interplay with gut microbiota for understanding the holistic actions of medicinal herbs by using calycosin-7-O-b-D-glucoside (C7G), the most abundant flavonoid and chemical marker in Astragali Radix, as a model compound. When C7G was orally administrated to rats, calycosin-39-O-glucuronide (G2) was the major circulating component in the blood together with a minor calycosin but not C7G. Rat gut microbiota hydrolyzed C7G in vitro rapidly and produced its aglycone calycosin. Calycosin exhibited higher permeability than C7G and further underwent extensive glucuronidation to yield 3ʹ-glucuronide as the dominant metabolite. Bioactivity assays revealed that G2 exhibited similar or more potent proangiogenic effects than calycosin in human umbilical vein endothelial cells in vitro and in the vascular endothelial growth factor receptor tyrosine kinase inhibitor II-induced blood vessel loss model in zebrafish. More interestingly, the incubation of C7G with gut microbiota from both normal and colitic rats showed a probiotics-like effect through stimulating the growth of the beneficial bacteria Lactobacillus and Bifidobacterium. In conclusion, C7G interacts reciprocally with gut microbiota after oral dosing, which makes it not only an angiogenic prodrug but also a modulator of gut microbiota.

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“…The sedative and partly the anticonvulsant actions are attributed to the activation of α 1 -containing receptors, while suppression of anxiety -to the α 2 /α 3 subtypes (RuDolPh & möhleR, 2006). Sedative effects have been demonstrated for flavonoids (maRtínez et al, 2009;ViSSiennona et al, 2011) and plant extracts containing procyanidins, flavonoids, and other polyphenols (Jiang et al, 2007). There are also data that flavonoids may have anxiolytic and sedative effects that could be mediated by activation of GABAergic nonbenzodiazepine binding sites (De caRValho et al, 2011).…”

Section: Effect Of Amfj On Locomotor Activitymentioning

confidence: 99%

Effects ofAronia melanocarpafruit juice on exploratory behaviour and locomotor activity in rats

Valcheva-Kuzmanova¹,

Eftimov²,

Tashev³

et al. 2014

Acta Alimentaria

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The main bioactive substances in Aronia melanocarpa fruit juice (AMFJ) are polyphenols (flavonoids, procyanidins, and phenolic acids). A great number of polyphenols are able to traverse the blood-brain barrier. In recent years more attention is drawn to the ability of these substances to influence central nervous system functions. The aim of the present study was to investigate the effects of AMFJ on exploratory behaviour and locomotor activity in male Wistar rats. AMFJ was administered orally for 7, 14, 21, and 30 days at three increasing doses (2.5, 5, and 10 ml kg -1 ). The changes in exploratory behaviour and locomotor activity were recorded in an Opto Varimex apparatus. It was found that the low doses of AMFJ (2.5 and 5 ml kg -1 ) for all treatment periods did not significantly affect exploratory behaviour and locomotor activity of rats compared to the saline-treated controls. AMFJ at the highest dose of 10 ml kg -1 had no significant effect on exploration and locomotion for the treatment periods of 7 and 14 days, while for the periods of 21 and 30 days it significantly decreased the number of horizontal and vertical movements, which might be the result of a sedative effect. At all the doses and testing periods, AMFJ did not disturb the progressive decrease in motor behaviour, suggesting habituation.Keywords: exploratory behaviour, locomotor activity, Aronia melanocarpa, ratsAronia melanocarpa (Michx.) Elliot, also known as black chokeberry, is a shrub, member of the Rosaceae family. Native to North America, it is now extensively cultivated in Europe. Aronia melanocarpa fruit juice (AMFJ) is one of the richest sources of natural polyphenols. These polyphenols are flavonoids (mainly from the subclass of anthocyanins), procyanidins, and phenolic acids (DeneV et al., 2012). Plant polyphenols are able to access the brain via the blood brain barrier and represent novel therapeutic agents in diseases of the central nervous system. In aged rats, anthocyanins from blueberry have been found in the cerebellum, cortex, hippocampus, or striatum in their unmetabolized forms (anDReS-lacueVa et al., 2005). These findings were the first to suggest the ability of polyphenolic compounds to cross the blood brain barrier and localize in various brain regions. WilliamS and co-workers (2008) reported that flavanol levels were higher than anthocyanin levels in brain tissue of aged rats supplemented with blueberries. RangeloRDonez and co-workers (2010) detected relatively high concentrations of quercetin in the hippocampus, striatum, and cerebellum.

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Route of administration determines the anxiolytic activity of the flavonols kaempferol, quercetin and myricetin — are they prodrugs?

Cited by 132 publications

References 43 publications

The mechanisms of action of St. John’s wort: an update

The mechanisms of action of St. John’s wort: an update

The Presystemic Interplay between Gut Microbiota and Orally Administered Calycosin-7-O-β-d-Glucoside

Effects ofAronia melanocarpafruit juice on exploratory behaviour and locomotor activity in rats

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