Antinociceptive, anti-inflammatory and anticonvulsant evaluation of the hydroethanolic leaf extract of calotropis procera (ait) r. Br. (apocynaceae)

ABSTRACT Pain, inflammation, and epilepsy remain a real and currently, a major problem in clinical medicine which requires new agents with improved efficacy for more effective therapy. Plant sources can serve as a basis for the search for these novel drugs. The analgesic, anti-inflammatory and anticonvulsant effects of hydroethanolic extract 70% v/v of Calotropis procera (CPE) which is widespread in Ghana and other tropical areas in the subregion was evaluated. A primary neurological assessment revealed that CPE has some central nervous system depressant and analgesic effects. It also showed impairment on motor coordination in the rotarod test. The extract potentiated duration of sleeping time in the pentobarbitone interaction test and analgesic properties were also further confirmed in the tail immersion test while it delayed pentylenetetrazole-induced convulsions. The anti-inflammatory assessment showed that CPE was able to significantly reduce both carrageenan-induced (F4,15=6.24, P=0.0105) and formalin-induced inflammation (F4,15=100.9, P<0.0001) in rats. The analgesic effects were demonstrated in the acetic acid-induced writhing and formalin-induced paw licking tests. Writhing induced by acetic acid was significantly reduced (F4,15=24.14, P<0.0001) on treatment with oral doses of CPE (30-300 mg/kg). The extract significantly inhibited both phase 1 and phase 2 states induced by injection of formalin (F4,60=12.21, P<0.0001) comparable to morphine, the standard analgesic used. The extract significantly attenuated hyper-nociception induced by tumour necrosis factor-alpha, interleukin 1β, bradykinin, and prostaglandin E2. The anti-nociceptive effect exhibited by CPE in the formalin test was reversed by systemic administration of naloxone and theophylline. The extract was further evaluated for anticonvulsant activity in rodents using animal models, picrotoxin–induced convulsions, strychnine-induced convulsions, and pilocarpine-induced status epilepticus. CPE (100–300 mg/kg) exhibited anticonvulsant effect against strychnine-induced clonic seizures by significantly reducing the duration (F6,20=4.196, P=0.0068) and frequency (F6,21=5.438, P=0.0016) of convulsions. The extract (100-300 mg kg-1) caused a profound dose-dependent delay in the onset of clonic convulsions induced by picrotoxin (F6,25=17.43, P<0.0001) and tonic convulsions (F6,20=43.45, P<0.0001) in mice. The duration of convulsions was reduced significantly (F6,19=41.71, P<0.0001). CPE (100-300 mg kg-1), showed profound anticonvulsant effect and protected against death induced the pilocarpine. ED50 (~ 0.1007) and Emax values calculated from the dose-response curves demonstrated that the extract was less potent than diazepam in reducing the duration and onset of convulsions but had comparable efficacies. Flumazenil – a GABAA receptor antagonist, did not reverse the onset or duration of convulsions produced by the extract in the picrotoxin-induced seizure model. Overall, the hydroethanolic leaf extract of Calotropis procera possesses analgesic, anti-inflammatory, and anticonvulsant properties.

Source: KNUST