Antinociceptive and anti-inflammatory activities of a sulfated polysaccharide isolated from the green seaweed Caulerpa cupressoides.
BACKGROUND
Red and brown algae sulfated polysaccharides (SPs) have been widely investigated as antinociceptive and/or anti-inflammatory agents; however, no description of these biological properties concerning green algae SPs have been reported. Caulerpa curpressoides (Chlorophyta) presents three SPs fractions (Cc-SP1, Cc-SP2, and Cc-SP3). Anticoagulant (in vitro) and anti- and pro-thrombotic (in vivo) effects of Cc-SP2 had been recently reported. We evaluated the effects of Cc-SP2 using models of nociception and acute inflammation in vivo.


METHODS
Male Swiss mice received Cc-SP2 (iv) 30 min prior to receiving 0.6% acetic acid (10 ml/kg, ip), 1% formalin (20 μl, sc) or were subjected to thermal stimuli (51 ± 1 °C). Cc-SP2 was injected sc to male Wistar rats in a peritonitis model or a paw edema model using carrageenan (ip or ipl, 500 μg). To analyze the systemic effects, Cc-SP2 (27 mg/kg, sc) was administrated to both genders mice before waiting for 14 days.


RESULTS
Cc-SP2 (3, 9 or 27 mg/kg) reduced (p < 0.05) the number of writhes induced by acetic acid by 57, 89.9 and 90.6%, respectively, the licking time in the first (9 or 27 mg/kg with 42.47 and 52.1%, respectively) and the second (3, 9 or 27 mg/kg with 68.95, 82.34 and 84.61%, respectively) phases. In the hot-plate test, the antinociceptive effect of Cc-SP2 (9 mg/kg) was primarily observed at 60 min (26.7 ± 1.2 s), with its effect reversed by naloxone (8.6 ± 1.3 s), suggesting the involvement of the opioid system. Cc-SP2 (3, 9 or 27 mg/kg, sc, p < 0.05) showed anti-inflammatory effects by decreasing neutrophils migration by 64, 69 and 73%, respectively, and potently reduced the paw edema, especially at the second (0.16 ± 0.02, 0.16 ± 0.03 and 0.12 ± 0.05 ml) and third (0.16 ± 0.03, 0.18 ± 0.02 and 0.14 ± 0.04 ml) hours, respectively. Cc-SP2 did not cause hepatic or renal alterations or affect body mass or the macroscopy of the organs examined (p > 0.05). Histopathological analyses of the liver and kidney showed that both organs were affected by Cc-SP2 treatment, but these effects were considered reversible.


CONCLUSIONS
The results indicate that the analgesic and anti-inflammatory effects of Cc-SP2 could be of biomedical applicability as a new, natural tool in pain and acute inflammatory conditions.
Northeast Biotechnology Network, Federal University of Ceará, Campus do Pici, Fortaleza, Ceará, Av Mister Hull, CEP 60455-760, Brazil.
José A G
JA
Rodrigues
Edfranck S O
ES
Vanderlei
Luana M C M
LM
Silva
Ianna W F
IW
Araújo
Ismael N L
IN
Queiroz
Gabriela A
GA
Paula
Ticiana M
TM
Abreu
Natássia A
NA
Ribeiro
Mirna M
MM
Bezerra
Hellíada V
HV
Chaves
Vilma
V
Lima
Roberta J B
RJ
Jorge
Helena S A
HS
Monteiro
Edda L
EL
Leite
Norma M B
NM
Benevides
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D046068:Caulerpa / Q000737:chemistry*; D000460:Chlorophyta / Q000737:chemistry*; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy*; D005260:Female; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009206:Myocardium / Q000473:pathology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D010538:Peritonitis / Q000188:drug therapy*; D011134:Polysaccharides / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011134:Polysaccharides