title: Anticonvulsant, anxiolytic and hypnotic effects of aqueous bulb extract of Crinum glaucum A. chev (Amaryllidaceae): role of GABAergic and nitrergic systems.
abstract: Crinum glaucum A. Chev (Amaryllidaceae) (CG) is a bulbous plant widely used in folk medicine in the treatment of cough, asthma and convulsions. This study was carried out to investigate the anticonvulsant, anxiolytic and hypnotic effects of the aqueous bulb extract of C. glaucum and its possible mechanism (s) of action. The anticonvulsant activity of C. glaucum extract (400-1200 mg kg(-1) p.o.) was investigated using picrotoxin, strychnine, isoniazid, pentylenetetrazol and N-methyl-D-aspartate (NMDA)-induced seizures in mice while the elevated plus maze test (EPM) and hexobarbitone-induced sleeping time (HIST) were used to evaluate the anxiolytic and hypnotic effects, respectively. Animals were pretreated with flumazenil (3 mg kg(-1); i.p. GABA(A) receptor antagonist), cyproheptadine (4 mg kg(-1); i.p. 5-HT2 receptor antagonist), L-arginine (500 mg kg(-1); p.o. Nitric Oxide (NO) precursor) and L-Nitroarginine (L-NNA) (10 mg kg(-1) i.p. Nitric Oxide Synthase (NOS) inhibitor) were used to investigate the probable mechanism (s) of anticonvulsant activity. Oral administration of CG significantly (p < 0.001) delayed the onset of seizures induced by picrotoxin, strychnine, isoniazid and pentylenetetrazol with peak effect at 1200 mg kg(-1) in comparison to control groups. CG (800 and 1200 mg kg(-1)) strongly antagonized NMDA-induced turning behavior. Pretreatment of mice with cyproheptadine could not reverse the anticonvulsant effect of CG. However, pretreatment with flumazenil and L-NNA significantly (p < 0.05) reversed the anticonvulsant effect of CG while L-arginine pretreatment significantly (p < 0.001) delayed the onset of seizures when compared with control and extract (1200 mg kg(-1) only). CG potentiated hexobarbitone-induced sleeping time with peak effect at 400 mg kg(-1) and also significantly (p < 0.05) increased open arm exploration in EPM and had its peak anxiolytic effect at 100 mg kg(-1). The data obtained suggests that aqueous bulb extract of Crinum glaucum possess anticonvulsant, anxiolytic and hypnotic activities which involve an interaction with GABAergic, nitrergic and glutaminergic systems to exert its effects.
authors: Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003, Idi-Araba, Lagos, Nigeria.
authors: Ismail O
authors: IO
authors: Ishola
authors: Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003, Idi-Araba, Lagos, Nigeria.
authors: Sunday O
authors: SO
authors: Olayemi
authors: Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, PMB 12003, Idi-Araba, Lagos, Nigeria.
authors: Abidemi R
authors: AR
authors: Idowu
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D031407:Crinum; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects* / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D026602:Nitrergic Neurons / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D010946:Plants, Medicinal; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D012890:Sleep / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D058787:GABA-A Receptor Antagonists; D006993:Hypnotics and Sedatives; D010936:Plant Extracts; D005973:Glutamine; D019001:Nitric Oxide Synthase