RESUMO
The Piper species chemistry has been widely investigated and the phytochemical analyses have led to the isolation of a number of active compounds like alkaloids, terpenes and flavones among others. The aim of this study was to evaluate the leishmanicidal activity of 2-[1-hydroxy-3-phenyl-(Z,2E)-2-propenylidene]-4-methyl-4-cyclopentene-1,3-dione (DCPC), a cyclopentenedione derivative isolated from the roots of Piper carniconnectivum C. DC., Piperaceae. Leishmanicidal activity against Leishmania amazonensis promastigotes was assessed, and the risk to host cell was assessed by measuring the cytotoxicity to peritoneal macrophages from BALB/c mice in vitro. L. amazonensis promastigotes and host macrophages were cultured in the presence of 100, 50, 25, 12.5 and 6 µg/mL of the cyclopentenedione derivative for up to 96 h. At the end of this period, the inhibitory concentrations (IC50) were compared with those from untreated cultures. The IC50 for promastigotes was 4.4 µg/mL after 96 h of treatment with the derivative. The 50% cytotoxic concentration (CC50) against murine peritoneal macrophages was 129 µg/mL. These results indicate that DCPC is a promising molecule for the development of leishmanicidal drugs.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Piper aleyreanum is a small tree that is widely distributed in tropical and subtropical regions, mostly in North and South America, and is used as an immunomodulator, analgesic and antidepressant in folk medicine. AIM OF THE STUDY: This study was designed to investigate the antinociceptive, anti-inflammatory and gastric antiulcer activities of the essential oils from the aerial parts of Piper aleyreanum (EOPa) in rodents. MATERIALS AND METHODS: The antinociceptive and anti-inflammatory effects of orally administered EOPa were evaluated in mice subjected to the formalin and pleurisy models, respectively. We also pretreated the rats with EOPa before acute ethanol-induced gastric lesions and measured gastric lesion extension and mucus and glutathione (GSH) levels in the gastric mucosa. Finally, we performed a phytochemical analysis of EOPa. RESULTS: The chemical composition of EOPa was analyzed by gas chromatography and mass spectrometry (GC/MS), which identified 35 compounds, representing 81.7% of total oil compounds. Caryophyllene oxide (11.5%), ß-pinene (9%), spathulenol (6.7%), camphene (5.2%), ß-elemene (4.7%), myrtenal (4.2%), verbenone (3.3%) and pinocarvone (3.1%) were the major oil constituents. The oral administration of EOPa (10-1000 mg/kg) significantly inhibited the neurogenic and inflammatory phases of formalin-induced licking, with ID50 values of 281.2 and 70.5 mg/kg, respectively. The antinociception caused by EOPa (100 mg/kg, p.o.) was not reversed by naloxone (1 or 5 mg/kg, i.p.) in the formalin test. EOPa (100-300 mg/kg, p.o.) did not affect animal motor coordination in an open-field model. In carrageenan-induced pleurisy, EOPa (1-100 mg/kg, p.o.) significantly decreased the total cell count, neutrophils and mononuclear cells with mean ID50 values of 53.6, 21.7 and 43.5 mg/kg, respectively. In addition, EOPa (1-30 mg/kg, p.o.) protected the rats against ethanol-induced gastric lesions with an ID50 value of 1.7 mg/kg and increased the mucus and GSH levels of the gastric mucosa to levels similar to those of the non-lesioned group. CONCLUSIONS: These data show for the first time that EOPa has significant antinociceptive and anti-inflammatory actions, which do not appear to be related to the opioid system. EOPa also has interesting gastroprotective effects related to the maintenance of protective factors, such as mucus production and GSH. These results support the widespread use of Piper aleyreanum in popular medicine and demonstrate that this plant has therapeutic potential for the development of phytomedicines with antinociceptive, anti-inflammatory and gastroprotective properties.