title: The antinociceptive activity of Muntingia calabura aqueous extract and the involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in its observed activity in mice.
abstract: The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking the dried leaves in distilled water (DH(2)O) (1 : 2; w/v) for 24 h, was prepared in concentrations of 10%, 50% and 100% that were approximately equivalent to doses of 27, 135 and 270 mg/kg, and administered subcutaneously (s.c.) 5 min after pre-treatment (s.c.) of mice with DH(2)O, L-arginine (20 mg/kg), N(G)-monomethyl-L-arginine acetate (L-NMMA; 20 mg/kg), N(G)-nitro-L-arginine methyl esters (L-NAME; 20 mg/kg), methylene blue (MB) (20 mg/kg), respectively. The AEMC was found to exhibit a concentration-dependent antinociception after pre-challenge with DH(2)O. Interestingly, pre-treatment with L-arginine was found to block significantly (P < 0.05) the AEMC antinociception but only at the highest concentration (100%) of AEMC used. On the other hand, pre-treatment with L-NAME was found to significantly (P < 0.05) enhance the low concentration but inhibit the high concentration AEMC antinociception. MB was found to significantly (P < 0.05) enhance AEMC antinociception at all concentrations used. Except for the higher concentration of AEMC used, co-treatment with L-NAME was found to insignificantly and significantly (P < 0.05) reverse the L-arginine effect when given alone or with low concentration AEMC, respectively. In addition, co-treatment with MB significantly (P < 0.05) reversed the L-arginine effect when given alone or with 10% concentration AEMC but failed to affect the activity of the rest of concentrations used. As a conclusion, this study has demonstrated the involvement of L-arginine/NO/cGMP pathway in AEMC antinociception.
authors.affiliation: School of Biotechnology and Life Sciences, Universiti Industri Selangor, Jalan Zirkon A7/A, Shah Alam, Selangor, Malaysia. shaza8174@hotmail.com
authors.forename: Zainul Amiruddin
authors.initials: ZA
authors.lastname: Zakaria
authors.forename: Mohd Roslan
authors.initials: MR
authors.lastname: Sulaiman
authors.forename: Abdul Manan Mat
authors.initials: AM
authors.lastname: Jais
authors.forename: Muhammad Nazrul
authors.initials: MN
authors.lastname: Somchit
authors.forename: Kogilla Vani
authors.initials: KV
authors.lastname: Jayaraman
authors.forename: Ganesh
authors.initials: G
authors.lastname: Balakhrisnan
authors.forename: Fatimah Corazon
authors.initials: FC
authors.lastname: Abdullah
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001120:Arginine / Q000378:metabolism* / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D045467:Elaeocarpaceae; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010147:Pain Measurement; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D018515:Plant Leaves; D015398:Signal Transduction / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019342:Acetic Acid; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester