title: Ilex paraguariensis hydroalcoholic extract exerts antidepressant-like and neuroprotective effects: involvement of the NMDA receptor and the L-arginine-NO pathway.
abstract: Ilex paraguariensis St. Hilaire (Aquifoliaceae) is a typical plant from South America. Preclinical studies have reported the effect of I. paraguariensis-based preparations on different alterations in the brain. This study aimed to examine the antidepressant-like and neuroprotective effects of I. paraguariensis hydroalcoholic extract (IpHE). The role of the N-methyl-D-aspartate receptor and the L-arginine-nitric oxide pathway in the IpHE antidepressant-like effect was also evaluated. Using the tail suspension test, we showed that IpHE (0.1-10 mg/kg, orally) exerts an antidepressant-like effect similar to that of ketamine (1 mg/kg, intraperitoneally). The antidepressant-like effect depends on the N-methyl-D-aspartate receptor and L-arginine-nitric oxide pathway modulation as we observed a combinatory effect using subeffective doses of IpHE (0.01 mg/kg, orally) and ketamine (0.1 mg/kg, intraperitoneally) or MK-801 (0.001 mg/kg, intraperitoneally). Also, pretreatment of mice with L-arginine (750 mg/kg, intraperitoneally) abolished the antidepressant-like effect of IpHE. This effect coincides with the neuroprotective effect, given that glutamate toxicity (10 mmol/l) did not decrease cell viability in hippocampal or cortical slices from IpHE-treated mice. The chromatographic profile of IpHE showed the presence of the methylxanthines caffeine and theobromine. Administration of methylxanthines (2.7 µg/kg) in mice produced an antidepressant-like effect, but not neuroprotection. We suggest that methylxanthines are at least in part responsible for the antidepressant-like effect of IpHE; further studies are necessary to determine the biological compounds responsible for the neuroprotective effect.
authors.affiliation: aPharmacy School, Universidade do Contestado, Canoinhas bDepartment of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis cDepartment of Pharmaceutical Sciences, Health Sciences Center, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Fabiana K
authors.initials: FK
authors.lastname: Ludka
authors.forename: Lori de Fátima
authors.initials: Lde F
authors.lastname: Tandler
authors.forename: Gislaine
authors.initials: G
authors.lastname: Kuminek
authors.forename: Gislaine
authors.initials: G
authors.lastname: Olescowicz
authors.forename: Jonatha
authors.initials: J
authors.lastname: Jacobsen
authors.forename: Simone
authors.initials: S
authors.lastname: Molz
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D001120:Arginine / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D030019:Ilex paraguariensis / Q000737:chemistry*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013020:South America
chemical_list: D000928:Antidepressive Agents; D018696:Neuroprotective Agents; D010936:Plant Extracts; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D001120:Arginine