Anxiolytic-like activity of 5-methoxyflavone in mice with involvement of GABAergic and serotonergic systems - in vivo and in silico evidences
Copyright © 2020. Published by Elsevier B.V..
Anxiety disorders are common worldwide and novel compounds are investigated for anxiolytic effect. A few studies have demonstrated the anxiolytic-like activity of natural and synthetic flavonoids. 5-methoxyflavone, a synthetic flavone derivative, has been reported to exhibit central nervous system depressant (sedative-hypnotic) effect in an earlier study. The present study was designed to investigate whether 5-methoxyflavone possesses anxiolytic-like activity in mice by employing two unconditioned models of anxiety such as elevated plus maze and light-dark box test. The possible role played by GABAergic (GABAA) and serotonergic (5HT1A) systems in the anxiolytic-like effect of 5-methoxyflavone was also investigated in the elevated plus maze test. Molecular docking studies were performed to ascertain the interaction of 5-methoxyflavone with GABAA (α2 subunit-containing) and 5HT1A receptors. 5-methoxyflavone treatment in mice (10, 20 or 40 mg/kg, i.p) increased the number of entries and time spent in the open arms in an elevated plus maze (p < 0.001). In the light-dark box test a significant increase in the time spent in light compartment (p < 0.001) and prolonged latency to enter the dark compartment (p < 0.01) were also observed. Pretreatment of mice with 5HT1A antagonist pindolol (10 mg/kg, i.p) or GABAA antagonist bicuculline (2 mg/kg, i.p) significantly attenuated the effect of 5-methoxyflavone in the elevated plus maze test. In silico studies provided evidences for good binding affinity of 5-methoxyflavone towards GABAA (α2 subunit-containing) and serotonergic (5HT1A) receptors by H-bond interactions. In conclusion, the present study identified a novel anxiolytic-like effect of 5-methoxyflavone involving GABAergic and serotonergic mechanisms.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology - 36(2020) vom: 15. Juli, Seite 100-110 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shanmugasundaram, Jaikumar [VerfasserIn] |
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| Links: |
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| Themen: |
5-methoxyflavone |
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| Anmerkungen: |
Date Completed 10.08.2021 Date Revised 10.08.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.euroneuro.2020.05.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311139418 |
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| 245 | 1 | 0 | |a Anxiolytic-like activity of 5-methoxyflavone in mice with involvement of GABAergic and serotonergic systems - in vivo and in silico evidences |
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| 520 | |a Copyright © 2020. Published by Elsevier B.V. | ||
| 520 | |a Anxiety disorders are common worldwide and novel compounds are investigated for anxiolytic effect. A few studies have demonstrated the anxiolytic-like activity of natural and synthetic flavonoids. 5-methoxyflavone, a synthetic flavone derivative, has been reported to exhibit central nervous system depressant (sedative-hypnotic) effect in an earlier study. The present study was designed to investigate whether 5-methoxyflavone possesses anxiolytic-like activity in mice by employing two unconditioned models of anxiety such as elevated plus maze and light-dark box test. The possible role played by GABAergic (GABAA) and serotonergic (5HT1A) systems in the anxiolytic-like effect of 5-methoxyflavone was also investigated in the elevated plus maze test. Molecular docking studies were performed to ascertain the interaction of 5-methoxyflavone with GABAA (α2 subunit-containing) and 5HT1A receptors. 5-methoxyflavone treatment in mice (10, 20 or 40 mg/kg, i.p) increased the number of entries and time spent in the open arms in an elevated plus maze (p < 0.001). In the light-dark box test a significant increase in the time spent in light compartment (p < 0.001) and prolonged latency to enter the dark compartment (p < 0.01) were also observed. Pretreatment of mice with 5HT1A antagonist pindolol (10 mg/kg, i.p) or GABAA antagonist bicuculline (2 mg/kg, i.p) significantly attenuated the effect of 5-methoxyflavone in the elevated plus maze test. In silico studies provided evidences for good binding affinity of 5-methoxyflavone towards GABAA (α2 subunit-containing) and serotonergic (5HT1A) receptors by H-bond interactions. In conclusion, the present study identified a novel anxiolytic-like effect of 5-methoxyflavone involving GABAergic and serotonergic mechanisms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 5-methoxyflavone | |
| 650 | 4 | |a Anxiolytic-like activity | |
| 650 | 4 | |a Docking | |
| 650 | 4 | |a GABA(A) (α(2) subunit-containing) receptor | |
| 650 | 4 | |a Serotonergic (5-HT(1A)) receptor | |
| 650 | 7 | |a 5-methoxyflavone |2 NLM | |
| 650 | 7 | |a Anti-Anxiety Agents |2 NLM | |
| 650 | 7 | |a Flavones |2 NLM | |
| 700 | 1 | |a Subramanian, Viswanathan |e verfasserin |4 aut | |
| 700 | 1 | |a Nadipelly, Jagan |e verfasserin |4 aut | |
| 700 | 1 | |a Kathirvelu, Parimala |e verfasserin |4 aut | |
| 700 | 1 | |a Sayeli, Vijaykumar |e verfasserin |4 aut | |
| 700 | 1 | |a Cheriyan, Binoy Varghese |e verfasserin |4 aut | |
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