title: Anticonvulsant screening of luteolin in four mouse seizure models.
abstract: Luteolin, a common plant polyphenolic flavonoid, has antioxidant, neuroprotective, anxiolytic and anti-inflammatory properties, which led us to hypothesize that luteolin is anticonvulsant. Here, we evaluated the effects of acute and chronic luteolin injection (i.p.) in four mouse seizure models, the 6 Hz model, maximal electroshock test (MEST), pentylenetetrazole (PTZ) and second hit PTZ test in the chronic stage of the pilocarpine model. Using real-time PCR mRNA levels of toll like receptor 4 (Tlr4), were quantified in the pilocarpine model, because luteolin has been shown to block the downstream signaling of TLR4. Luteolin did not exhibit any consistent anti- or pro-convulsant actions after single dosing in the 6 Hz (0.3-10 mg/kg), MEST (0.3-20 mg/kg) and PTZ (3 mg/kg) tests, nor after repeated daily dosing (10 mg/kg) in the 6 Hz model. Tlr4 mRNA levels were upregulated 3 days after pilocarpine-induced status epilepticus (SE), but unaltered at three weeks in the chronic stage of the model. At that time, there was no effect of repeated luteolin injections (10 mg/kg, i.p.) in the second hit PTZ test, indicating that TLR-4 signaling may be not one of the main players determining the seizure threshold in this seizure model. In summary, we found no indications that luteolin is pro- or anti-convulsant in one chronic and three acute mouse seizure models.
authors.affiliation: School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Mohd Farooq
authors.initials: MF
authors.lastname: Shaikh
authors.forename: Kah Ni
authors.initials: KN
authors.lastname: Tan
authors.forename: Karin
authors.initials: K
authors.lastname: Borges
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D047311:Luteolin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D010862:Pilocarpine; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D010862:Pilocarpine; D047311:Luteolin; D010433:Pentylenetetrazole
keywords: 6Hz; Flavonoid; Inflammation; Pentylenetetrazole; Pilocarpine; TLR4