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      Ginkgo biloba extract (GbE) attenuates obesity and anxious/depressive-like behaviours induced by ovariectomy

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          Abstract

          While several pieces of evidence link obesity and mood disorders in menopause, the mechanisms involved are not yet fully understood. We have previously demonstrated that Ginkgo biloba extract (GbE) both attenuated diet-induced obesity of male rats and restored serotonin-induced hypophagia in ovariectomized female rats. The present study aimed at exploring whether GbE treatment ameliorates ovariectomy-related obesity and anxious/depressive-like behaviours. Wistar female rats were either ovariectomized (OVX) or sham-operated (Sham). After 2 months, either 500 mg/kg of GbE or vehicle were administered daily by gavage for 14 days. Anxious/depressive-like behaviours were assessed by the Elevated Plus Maze and the Forced Swim Tests, respectively. Ovariectomy caused high visceral adiposity, hyperleptinemia, and hypercholesterolemia, and increased the anxiety index ( p = 0.048 vs. Sham + GbE) while it decreased the latency to immobility ( p = 0.004 vs. Sham). GbE treatment in OVX rats improved body composition, adiponectin levels and blood lipid profile. It also reduced the anxiety index ( p = 0.004) and increased the latency to immobility ( p = 0.003) of OVX rats. Linear regression analysis demonstrated that leptin ( p = 0.047) and total cholesterol levels ( p = 0.022) were associated with anxious-like behaviours while body adiposity ( p = 0.00005) was strongly associated with depressive-like behaviours. The results showed that GbE therapy was effective in attenuating the deleterious effects of ovariectomy on body composition, lipid profile, and anxious/depressive-like behaviours. Further studies are warranted to better understand the therapeutic potential of GbE in menopause.

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          Behavioural despair in rats: a new model sensitive to antidepressant treatments.

          Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity. Anxiolytic compounds did not affect immobility whereas major tranquilisers enhanced it. Immobility was also reduced by electroconvulsive shock, REM sleep deprivation and "enrichment" of the environment. It was concluded that immobility reflects a state of lowered mood in the rat which is selectively sensitive to antidepressant treatments. Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests.
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            Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat.

            A novel test for the selective identification of anxiolytic and anxiogenic drug effects in the rat is described, using an elevated + -maze consisting of two open arms and two enclosed arms. The use of this test for detecting such drug effects was validated behaviourally, physiologically, and pharmacologically. Rats made significantly fewer entries into the open arms than into the closed arms, and spent significantly less time in open arms. Confinement to the open arms was associated with the observation of significantly more anxiety-related behaviours, and of significantly greater plasma corticosterone concentrations, than confinement to the closed arms. Neither novelty nor illumination was a significant contributor to the behaviour of the rats on the + -maze. A significant increase in the percentage of time spent on the open arms and the number of entries into the open arms was observed only within clinically effective anxiolytics (chlordiazepoxide, diazepam and, less effectively, phenobarbitone). Compounds that cause anxiety in man significantly reduced the percentage of entries into, and time spent on, the open arms (yohimbine, pentylenetetrazole, caffeine, amphetamine). Neither antidepressants nor major tranquilisers had a specific effect. Exposure to a holeboard immediately before placement on the + -maze showed that behaviour on the maze was not clearly correlated either with exploratory head-dipping or spontaneous locomotor activity.
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              Inflammation: depression fans the flames and feasts on the heat.

              Depression and inflammation fuel one another. Inflammation plays a key role in depression's pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health.
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                Author and article information

                Contributors
                eliane.beraldi@gmail.com
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                8 January 2021
                8 January 2021
                2021
                : 11
                : 44
                Affiliations
                [1 ]GRID grid.411249.b, ISNI 0000 0001 0514 7202, Disciplina de Fisiologia da Nutrição, Departamento de Fisiologia, , Universidade Federal de São Paulo, ; Rua Botucatu, 862, Edifício de Ciências Biomédicas, 2º andar, Vila Clementino, São Paulo, SP CEP: 04023-062 Brasil
                [2 ]GRID grid.411249.b, ISNI 0000 0001 0514 7202, Setor de Fisiologia e Farmacologia, Departamento de Ciências Biológicas, , Universidade Federal de São Paulo, ; Diadema, SP Brasil
                Article
                78528
                10.1038/s41598-020-78528-3
                7794418
                33420094
                f53f3a74-7af5-41cf-9eda-ff1b02dc6523
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 February 2020
                : 9 November 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002322, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior;
                Funded by: FundRef http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 453924/2014-0
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001807, Fundação de Amparo à Pesquisa do Estado de São Paulo;
                Award ID: 2012/03172-4
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                metabolism,endocrine system and metabolic diseases,anxiety,depression
                Uncategorized
                metabolism, endocrine system and metabolic diseases, anxiety, depression

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