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Year : 2019  |  Volume : 15  |  Issue : 62  |  Page : 62-70

The contribution of ionotropic gabaergic and N-methyl-D-Aspartic acid receptors in the antidepressant-like effects of hispidulin

1 Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia
2 Department of Pharmacy, University of Swabi, Pakistan
3 Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa, Pakistan

Correspondence Address:
Abeer Abdelhalim
Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pm.pm_539_18

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Background: Salvia triloba, commonly known as sage belongs to Lamiaceae family, is conventionally used as a brain-enhancing tonic. The purpose of this study was to evaluate hispidulin, a flavonoid isolated from S. triloba for its antidepressant-like effects and to identify its possible mechanisms of action. Materials and Methods: Mouse models of the forced swimming test (FST) and tail-suspension test (TST) were used to assess the antidepressant-like effects of hispidulin. Results: The results showed that hispidulin at the doses level of 1–10 mg/kg, intraperitoneal (ip) exerted significant antidepressant-like effects in both FST and TST. Pretreatment of animals with bicuculline (4 mg/kg, ip; a competitive γ-aminobutyric acid (GABA) antagonist) and N-methyl-D-aspartic acid (NMDA) (75 mg/kg, ip, glutamate receptor agonist) significantly blocked the reduction in immobility time of mice treated with hispidulin (3 mg/kg, ip) in FST. Furthermore, brain GABA levels were significantly decreased by coadministration of hispidulin with bicuculline, whereas glutamate levels were increased with combined administration of hispidulin and NMDA. Moreover, coadministration of sub-effective doses of hispidulin (0.5 mg/kg, ip) and ketamine (0.3 mg/kg, ip) or MK 801 (0.1 mg/kg, ip) also exerted significant antidepressant-like effects in FST. Conclusion: Taken together, these findings suggest that hispidulin possess significant antidepressant-like effects mediated most likely through GABAergic and glutamatergic mechanisms.

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