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Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved.

Sani MH, Zakaria ZA, Balan T, Teh LK, Salleh MZ - Evid Based Complement Alternat Med (2012)

Bottom Line: The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist.Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), N(G)-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception.In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, 43400 Serdang, Malaysia.

ABSTRACT
Muntingia calabura L. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC) and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), N(G)-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

No MeSH data available.


Related in: MedlinePlus

Effect of MEMC in formalin-induced paw licking test. Graph A shows early phase activity, while graph B shows the late phase analgesic effect. Each column represents the mean ± SEM of 6 rats. The rats were pretreated with vehicle (10% DMSO), MEMC (100, 250, and 500 mg/kg, p.o.), acetylsalicylic acid (ASA, p.o.), or morphine (5 mg/kg, p.o.), 60 min before i.pl injection of formalin. The asterisks denote the significance levels as compared to control, ***P < 0.001 by one-way ANOVA followed by Dunnett's post hoc test. ***Data differed significantly (P < 0.05) when compared to the 10% DMSO-treated group.
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fig2: Effect of MEMC in formalin-induced paw licking test. Graph A shows early phase activity, while graph B shows the late phase analgesic effect. Each column represents the mean ± SEM of 6 rats. The rats were pretreated with vehicle (10% DMSO), MEMC (100, 250, and 500 mg/kg, p.o.), acetylsalicylic acid (ASA, p.o.), or morphine (5 mg/kg, p.o.), 60 min before i.pl injection of formalin. The asterisks denote the significance levels as compared to control, ***P < 0.001 by one-way ANOVA followed by Dunnett's post hoc test. ***Data differed significantly (P < 0.05) when compared to the 10% DMSO-treated group.

Mentions: Overall, the MEMC demonstrated a significant (P < 0.05) antinociceptive activity in both phases of the formalin-induced paw licking test (Figures 2(a) and 2(b)). The extract exhibited a dose-dependent effect in the early, but not late, phase with antinociceptive activity seen only with the 250 and 500 mg/kg MEMC, whereas, in the late phase, all doses of MEMC exerted significant (P < 0.05) antinociceptive activity in a dose-independent manner and almost equivalent strength. As a comparison to MEMC, 5 mg/kg morphine also attenuated both phases of nociception while 100 mg/kg ASA only reduced nociception in the late phase. Overall, morphine was effective than ASA and MEMC in both phases of formalin test, while ASA was effective than MEMC in the late phase of the same test.


Antinociceptive Activity of Methanol Extract of Muntingia calabura Leaves and the Mechanisms of Action Involved.

Sani MH, Zakaria ZA, Balan T, Teh LK, Salleh MZ - Evid Based Complement Alternat Med (2012)

Effect of MEMC in formalin-induced paw licking test. Graph A shows early phase activity, while graph B shows the late phase analgesic effect. Each column represents the mean ± SEM of 6 rats. The rats were pretreated with vehicle (10% DMSO), MEMC (100, 250, and 500 mg/kg, p.o.), acetylsalicylic acid (ASA, p.o.), or morphine (5 mg/kg, p.o.), 60 min before i.pl injection of formalin. The asterisks denote the significance levels as compared to control, ***P < 0.001 by one-way ANOVA followed by Dunnett's post hoc test. ***Data differed significantly (P < 0.05) when compared to the 10% DMSO-treated group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351243&req=5

fig2: Effect of MEMC in formalin-induced paw licking test. Graph A shows early phase activity, while graph B shows the late phase analgesic effect. Each column represents the mean ± SEM of 6 rats. The rats were pretreated with vehicle (10% DMSO), MEMC (100, 250, and 500 mg/kg, p.o.), acetylsalicylic acid (ASA, p.o.), or morphine (5 mg/kg, p.o.), 60 min before i.pl injection of formalin. The asterisks denote the significance levels as compared to control, ***P < 0.001 by one-way ANOVA followed by Dunnett's post hoc test. ***Data differed significantly (P < 0.05) when compared to the 10% DMSO-treated group.
Mentions: Overall, the MEMC demonstrated a significant (P < 0.05) antinociceptive activity in both phases of the formalin-induced paw licking test (Figures 2(a) and 2(b)). The extract exhibited a dose-dependent effect in the early, but not late, phase with antinociceptive activity seen only with the 250 and 500 mg/kg MEMC, whereas, in the late phase, all doses of MEMC exerted significant (P < 0.05) antinociceptive activity in a dose-independent manner and almost equivalent strength. As a comparison to MEMC, 5 mg/kg morphine also attenuated both phases of nociception while 100 mg/kg ASA only reduced nociception in the late phase. Overall, morphine was effective than ASA and MEMC in both phases of formalin test, while ASA was effective than MEMC in the late phase of the same test.

Bottom Line: The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist.Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), N(G)-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception.In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Selangor, 43400 Serdang, Malaysia.

ABSTRACT
Muntingia calabura L. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract of M. calabura leaves (MEMC) and to elucidate the possible mechanism of antinociception involved. The in vivo chemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P < 0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), N(G)-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P < 0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

No MeSH data available.


Related in: MedlinePlus