Antinociceptive activity of the monoterpene α-phellandrene in rodents: possible mechanisms of action.

OBJECTIVES: The aim of this work was to investigate the antinociceptive property of α-phellandrene (α-PHE) in experimental nociception models and possible mechanisms involved. METHODS: Mass spectrometry was used to evaluate the purity and molecular mass of α-PHE. Macrophages from mice peritoneal cavity were used in an MTT test. Rodents were used in tests of chemical and mechanical nociception. In the study of the mechanisms, the animals were treated with pharmacological tools and then submitted to the glutamate test. KEY FINDINGS: α-PHE purity was 98.2% and molecular mass 136.1 Da. α-PHE did not show cytotoxicity. In the writhing and capsaicin tests, α-PHE promoted the antinociceptive effect in all evaluated doses (minimum dose 3.125 mg/kg). In the formalin test, α-PHE (50 mg/kg) was effective in inhibiting both phases. In the glutamate test, the monoterpene (12.5 mg/kg) decreased the nociceptive response. In carrageenan-induced hyperalgesia, α-PHE (50 mg/kg) decreased the hypernociception index. In the study of the mechanisms involved, pretreatment with naloxone reversed the α-PHE antinociceptive effect, the same occurred with glibenclamide, l-arginine, atropine and yohimbine. α-PHE did not show muscle relaxant activity or central depressant effects in open field and rota rod tests. CONCLUSIONS: α-PHE has an antinociceptive effect and it possibly involves the glutamatergic, opioid, nitrergic, cholinergic and adrenergic systems.

Evaluation of the in vitro Activity of Dermaseptin 01, a CationicAntimicrobial Peptide, against Schistosoma mansoni

Schistosomiasis is a neglected tropical disease that remains a considerable public health problem worldwide. Since the mainstay of schistosomiasis control is chemotherapy with a single drug,praziquantel, drug resistance is a concern. Here, we examined the in vitro effects of dermaseptin 01(DS 01), an antimicrobial peptide found in the skin secretion of frogs of the genus Phyllomedusa, onSchistosoma mansoni adult worms. DS 01 at a concentration of 100 mg/ml reduced the worm motor activity and caused the death of all worms within 48 h in RPMI 1640 medium. At the highest sublethal concentration of antimicrobial peptide (75 mg/ml), a 100% reduction in egg output of paired female worms was observed. Additionally, DS 01 induced morphological alterations on the tegument of S. mansoni, and a quantitative analysis carried out by confocal microscopy revealed extensive destruction of the tubercles in a dose-dependent manner over the concentration range of 50 –200 mg/ml. It was the first time that an anthelmintic activity towards schistosomes has been reported for a dermaseptin.

Evaluation of the in vitro activity of dermaseptin 01, a cationic antimicrobial peptide, against Schistosoma mansoni.

Schistosomiasis is a neglected tropical disease that remains a considerable public health problem worldwide. Since the mainstay of schistosomiasis control is chemotherapy with a single drug, praziquantel, drug resistance is a concern. Here, we examined the in vitro effects of dermaseptin 01 (DS 01), an antimicrobial peptide found in the skin secretion of frogs of the genus Phyllomedusa, on Schistosoma mansoni adult worms. DS 01 at a concentration of 100 µg/ml reduced the worm motor activity and caused the death of all worms within 48 h in RPMI 1640 medium. At the highest sublethal concentration of antimicrobial peptide (75 µg/ml), a 100% reduction in egg output of paired female worms was observed. Additionally, DS 01 induced morphological alterations on the tegument of S. mansoni, and a quantitative analysis carried out by confocal microscopy revealed extensive destruction of the tubercles in a dose-dependent manner over the concentration range of 50-200 µg/ml. It was the first time that an anthelmintic activity towards schistosomes has been reported for a dermaseptin.