Anti-allodynic and anti-oedematogenic properties of the extract and lignans from Phyllanthus amarus in models of persistent inflammatory and neuropathic pain.
This study investigated the anti-allodynic and anti-oedematogenic effects of the hexanic extract, lignan-rich fraction and purified lignans from a plant used in the traditional medicine, Phyllanthus amarus, in the inflammatory and neuropathic models of nociception. The hexanic extract inhibited the allodynia and the oedema induced by the intraplantar injection of complete Freund's adjuvant (CFA). The inhibition observed was 76 +/- 7% (ipsilateral paw), 64 +/- 7% (contralateral paw), and 41 +/- 2% (oedema). Otherwise, the lignan-rich fraction or the pure lignans did not affect CFA-induced allodynia. Administered chronically, the lignan fraction reduced CFA-induced paw oedema (39 +/- 9%). When evaluated in the model of neuropathic pain caused by partial ligation of sciatic nerve, the hexanic extract inhibited the mechanical allodynia (77 +/- 7%), with a similar efficacy to the gabapentin (71 +/- 10%). The anti-allodynic effects of hexanic extract of P. amarus seem not to be associated with the impairment of motor co-ordination or with the development of tolerance. Finally, the treatment with hexanic extract inhibited the increase of myeloperoxidase activity, either following intraplantar injection of CFA or after sciatic nerve injury. It is concluded that, apart from its anti-inflammatory actions, which are probably linked to the presence of lignans, another as yet unidentified active principle(s) present in the hexanic extract of P. amarus produces pronounced anti-allodynia in two models of inflammatory and neuropathic pain. Considering that few drugs are currently available for the treatment of chronic pain, especially of the neuropathic type, the present results may have clinical relevance and open new possibilities for the development of new anti-allodynic drugs.
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, 88015-420 Florianópolis, SC, Brazil.
Cândida A L
CA
Kassuya
Aline A
AA
Silvestre
Vera Lúcia G
VL
Rehder
João B
JB
Calixto
D000085:Acetates / Q000494:pharmacology; D000588:Amines; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005620:Freund's Adjuvant; D000077206:Gabapentin; D006586:Hexanes; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008026:Ligation; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy*; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D029803:Phyllanthus / Q000737:chemistry*; D010812:Physical Stimulation; D010936:Plant Extracts / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D012585:Sciatica / Q000188:drug therapy / Q000473:pathology; D012997:Solvents; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D006586:Hexanes; D017705:Lignans; D010936:Plant Extracts; D012997:Solvents; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D005620:Freund's Adjuvant; D009195:Peroxidase