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

• Published in: Pharmacognosy Magazine Vol. 15; no. 62; pp. 62 - 70
• Main Authors: Abdelhalim, Abeer, Khan, Imran, Karim, Nasiara
• Format: Journal Article
• Language: English
• Published: Bangalore Wolters Kluwer India Pvt. Ltd 01-04-2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd
• Subjects: Acids; Amino acids; Animals; Antidepressants; Aspartate; Brain research; Chemical properties; Dopamine; Drugs; Flavonoids; GABA; Health aspects; Ketamine; Mental depression; Mental disorders; N-methyl-D-aspartate; Natural products; Pharmacognosy; Pharmacological research; Physiological aspects; Salvia; Studies; Swimming; Pakistan; Antidepressant; GABAergic; Hispidulin; glutamatergic; tail-suspension test; forced swim test
• ISSN: 0973-1296; 0976-4062
• DOI: 10.4103/pm.pm_539_18

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.