Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: Possible role of l-arginine-NO-cGMP pathway and BDNF levels

Donato, Franciele; Gomes, Marcelo Gomes de; Goes, André Tiago Rossito; Filho, Carlos Borges; Fabbro, Lucian Del; Antunes, Michelle S.; Souza, Leandro Cattelan; Boeira, Silvana Peterini; Jessé, Cristiano Ricardo

doi:10.1016/j.brainresbull.2014.03.004

Cited by 97 publications

(67 citation statements)

References 45 publications

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“…antibacterial, anti-inflammatory and anti-angiogenic properties [43,44]. When regards hesperetine, authors indicate on its antiallergic, antidepressant and memory improving effect [45,46]. In turn, scutellarin reveals antihypertensive and antivirus [47,48], while chrysin -antitumor, anxiolytic and anticonvulsant activities [49][50][51][52].…”

Section: Resultsmentioning

confidence: 99%

Experimental Paper. Intrapopulation variability of flavonoid content in roots of Baikal skullcap (Scutellaria baicalensis Georgi)

Kosakowska

2017

Herba Polonica

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SummaryIntroduction: Baikal skullcap (Scutellaria baicalensis Georgi) is an important medicinal plant, indigenous to Asia. Due to a wide range of pharmacological activities, its roots has been used for ages in Traditional Chinese Medicine. Recently, the species has become an object of interest of Western medicine, as well. Objective: The aim of the study was to determine the variability of Baikal skullcap population originated from Mongolia and cultivated in Poland, in terms of content and composition of flavonoids in the roots. Methods: The objects of the study were 15 individual plants, selected within examined population and cloned in order to obtain a sufficient amount of raw material. The total content of flavonoids in roots was determined according to Polish Pharmacopeia 6th. The qualitative analysis of flavonoids was carried out using HPLC, Shimadzu chromatograph. Results: The dry mass of roots ranged from 25.88 to 56.14 g × plant-1. The total content of flavonoids (expressed as a quercetin equivalent) varied between 0.17 and 0.52% dry matter (DM). Nine compounds were detected within the group, with oroxylin A 7-Oglucuronide (346.90-1063.00 mg × 100 g-1DM) as a dominant, which differentiated investigated clones at the highest degree (CV=0.27). Baicalin (391.40-942.00 mg × 100 g-1DM), wogonoside (324.00-641.10 mg × 100 g-1DM) and hesperetine 7-O-glucoside (163.00-346.32 mg × 100 g-1DM) were also present in a considerable amounts. Clone 7 was distinguished by the highest content of all investigated compounds, except wogonin and oroxylin A 7-O-glucuronide. Conclusions: Results obtained in present study show a high variability within Baical skullcap investigated population in respect of flavonoid compounds detected in roots. Thus, the results may be used in future investigations concerning the selection and breeding of this species.

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Section: Resultsmentioning

confidence: 99%

Experimental Paper. Intrapopulation variability of flavonoid content in roots of Baikal skullcap (Scutellaria baicalensis Georgi)

Kosakowska

2017

Herba Polonica

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“…For example, depressed patients exhibit elevated plasma nitrate levels (9), whereas pre-clinical studies have demonstrated antidepressant-like effects following the local or systemic administration of NOS inhibitors (10)(11)(12)(13)(14)(15)(16). Furthermore, the Glu/NMDAR/NO/cGMP pathway has been shown to be involved in the antidepressantlike activity of a range of different drugs using rodent models (11)(12)(13)(17)(18)(19)(20)(21)(22). The specific brain area(s) that are involved in these effects remain unclear, but it appears that the hippocampus may play an important role.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression

Liebenberg

Joca

Wegener

2014

Acta Neuropsychiatr.

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Liebenberg N, Joca S, Wegener G. Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression.Objective: We investigated whether the nitric oxide (NO) precursor, L-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-D-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine. Methods: Flinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) with L-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluated ex vivo in the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activity and cGMP concentration. Results: L-Arginine pre-treatment prevented the antidepressant-like effect of ketamine in the FST, as well as a ketamine-induced increase in cGMP levels in the frontal cortex and hippocampus of FSL rats. Ketamine reduced cNOS activity only in the hippocampus, and this effect was not reversed by L-arginine. Conclusion: Both the behavioural and molecular results from this study indicate an involvement for the NO signalling pathway in the antidepressant action of ketamine. Although not easily interpretable, these findings broaden our knowledge of effects of ketamine on the NO system. Signficant outcomes• The behavioural results indicate the involvement of the nitric oxide (NO) signalling system in the antidepressant-like action of ketamine;• The molecular data reveals ketamine-induced changes in NO signalling in the frontal cortex and hippocampus, and indicates that increased cyclic guanosine monophosphate (cGMP) levels may be important for the antidepressant action of ketamine. Limitations• The behavioural test used in this study is not appropriate for the evaluation of onset of action of antidepressants, and the results can therefore not reveal whether NO signalling is specifically involved in the time of onset of ketamine's antidepressant effect.• The observation that L-arginine on its own did not increase, but instead decreased constitutive NOS (cNOS) activity in both brain regions tested, complicates the interpretation of the results. 90https://www.cambridge.org/core/terms. https://doi

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“…This effect may also be partially mediated through the increase of hippocampal brain-derived neurotrophic factor levels. 7 Potassium (K + ) channels are a key component of this electrical circuit and are controlled either by an electrical impulse or through signaling molecules. 8 The association of K + channels in the modulation of depression has been suggested by several preclinical studies.…”

Section: Introduction Dmentioning

confidence: 99%

Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice

Donato

Filho

Giacomeli

et al. 2015

Journal of Medicinal Food

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The administration of hesperidin elicits an antidepressant-like effect in mice by a mechanism dependent on an interaction with the l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, whose stimulation is associated with the activation of potassium (K + ) channels. Thus, this study investigated the involvement of different types of K + channels in the antidepressant-like effect of hesperidin in the mice tail suspension test (TST). The intracerebroventricular administration of tetraethylammonium (TEA, a nonspecific blocker of K + channels), glibenclamide (an ATP-sensitive K + channel blocker), charybdotoxin (a large-and intermediate-conductance calcium-activated K + channel blocker) or apamin (a small-conductance calcium-activated K + channel blocker) combined with a subeffective dose of hesperidin (0.01 mg/kg, intraperitoneally [i.p.]) was able to produce a synergistic antidepressant-like effect in the mice TST. Moreover, the antidepressant-like effect elicited by an effective dose of hesperidin (0.3 mg/kg, i.p.) in TST was abolished by the treatment of mice with pharmacological compounds K + channel openers (cromakalim and minoxidil). Results showed that the antidepressantlike effect of hesperidin in TST may involve, at least in part, the modulation of neuronal excitability through inhibition of K + channels and may act through a mechanism dependent on the inhibition of l-arginine-NO pathway.

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Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: Possible role of l-arginine-NO-cGMP pathway and BDNF levels

Cited by 97 publications

References 45 publications

Experimental Paper. Intrapopulation variability of flavonoid content in roots of Baikal skullcap (Scutellaria baicalensis Georgi)

Experimental Paper. Intrapopulation variability of flavonoid content in roots of Baikal skullcap (Scutellaria baicalensis Georgi)

Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression

Evidence for the Involvement of Potassium Channel Inhibition in the Antidepressant-Like Effects of Hesperidin in the Tail Suspension Test in Mice

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