Neurobehavioral and toxicological activities of two potentially CNS-acting medicinal plants of Piper genus

Plants from the genus Piper are economically useful and some species have been indicated because of their medicinal properties in the central nervous system. However, few studies about toxicity and neurobehavioral effects have been conducted. In this study, two Piper species, P. amalago and P. mikanianum were investigated in rats to determine acute toxicity and to evaluate the ansiogenic/ansiolytic properties in the elevated plus-maze and the effects on locomotion and exploration in an open field. Additionally, genotoxic activities were evaluated, using the comet assay in several tissues and the micronucleus assay in bone marrow. The phytochemical analysis of both Piper species leaves suggests the presence of amide, essential oils, flavonoids and phenolic compounds. The LD50 of P. amalago and P. mikanianum were estimated as 2,545 and 1,661 mg/kg, respectively. The behavioral and genotoxic parameters were determined after an intraperitoneal administration of P. amalago (250 or 420 mg/kg) or P. mikanianum (160 or 270 mg/kg). Both plants decreased the number of entries and time spent in the open arms in the plus-maze test, indicating an anxiogenic effect. Only P. mikanianum affected locomotion and exploration in the open field behavior test. No genotoxic or mutagenic effect was observed. Our results suggest that these Piper species act on the central nervous system, without induce genetic toxicity.