Methanol leaf extract of Paullinia pinnata exerts sleep-enhancing and anticonvulsant effects via a mechanism involving the GABAergic pathway.

Purpose: Leaf extracts of Paullinia pinnata L. (Sapindaceae) are used in ethnomedicine for the treatment of central nervous system-related diseases such as insomnia and epilepsy. We determined the bioactive constituents, sleep-enhancing and anti-convulsant potentials, and possible mechanisms of action of P. pinnata methanol leaf extract (PPME).

Methods: Gas Chromatography-Mass spectrometry (GC-MS) was used to identify the bioactive compounds in PPME. Adult Swiss albino mice were used. Oral LD was estimated before administering PPME at oral doses of 100, 200, and 400 mg/kg to test for sleep-enhancing and anticonvulsant properties. To evaluate the possible mechanisms involved, mice were pretreated for five days with isoniazid (NIH) a GABA synthesis inhibitor before re-evaluation of sleep-enhancing property. The activities of glutamic acid decarboxylase (GAD), superoxide dismutase (SOD), catalase (CAT), and the level of malondialdehyde (MAD) in the brain of mice were also evaluated after a 7-day treatment with the extract.

Results: Twenty-five phytochemical compounds were identified from GC-MS analysis with fatty acid esters of lauric and fumaric acids being the most abundant. The oral LD of PPME was estimated to be greater than 5000 mg/kg. Doses of PPME significantly (p < 0.001) reduced sleep latency and increased the duration of sleep of phenobarbital-treated mice. Except for 100 mg/kg, the doses also significantly protected mice against maximum electroshock (p < 0.001) and pentylenetetrazole (p < 0.05) but not strychnine-induced convulsions. Pretreatment with isoniazid (INH) almost completely reversed the sleep-enhancing effects of PPME. The activities of GAD, SOD, and CAT, and level of MDA in brains of the mice were significantly (p < 0.001) increased by doses of PPME administered for five days.

Conclusion: The extract possesses sleep-enhancing and anticonvulsant properties which depend on increased level of GABA in the brain. Its antioxidant action may be neuroprotective against free radicals-induced damage.