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Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system.

Shamima AR, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P - Int J Mol Sci (2012)

Bottom Line: Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system.Naloxonazine did inhibit the effect of MG, but it was not statistically significant.These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, Cyberjaya University College of Medical Sciences, 63000 Cyberjaya, Selangor, Malaysia; E-Mail: alfaqirah_msc@yahoo.com.

ABSTRACT
Cannabinoids and opioids systems share numerous pharmacological properties and antinociception is one of them. Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system. In the present study, the action of MG was investigated as the antinociceptive agent acting on Cannabinoid receptor type 1 (CB1) and effects on the opioids receptor. The latency time was recorded until the mice showed pain responses such as shaking, licking or jumping and the duration of latency was measured for 2 h at every 15 min interval by hot plate analysis. To investigate the beneficial effects of MG as antinociceptive agent, it was administered intraperitoneally 15 min prior to pain induction with a single dosage (3, 10, 15, 30, and 35 mg/kg b.wt). In this investigation, 35 mg/kg of MG showed significant increase in the latency time and this dosage was used in the antagonist receptor study. The treated groups were administered with AM251 (cannabinoid receptor-1 antagonist), naloxone (non-selective opioid antagonist), naltrindole (δ-opioid antagonist) naloxonazine (μ(1)-receptor antagonist) and norbinaltorpimine (κ-opioid antagonist) respectively, prior to administration of MG (35 mg/kg). The results showed that the antinociceptive effect of MG was not antagonized by AM251; naloxone and naltrindole were effectively blocked; and norbinaltorpimine partially blocked the antinociceptive effect of MG. Naloxonazine did inhibit the effect of MG, but it was not statistically significant. These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.

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Related in: MedlinePlus

Schematic representation of isolation of mitragynine from Mitragyna speciosa.
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f8-ijms-13-11427: Schematic representation of isolation of mitragynine from Mitragyna speciosa.

Mentions: One kilogram leaves of MS was cleaned and dried with constant temperature at 45 °C overnight before grinded into powder form. It was then macerated with absolute methanol for 72 h. The mixture was filtered to remove filtrate from insoluble particles to obtain the methanol extract. Extract was evaporated using rotary evaporator (Eyela, Japan) at a temperature below 55 °C. The methanol extract was added with 5% sulphuric acid and extensively stirred overnight. The mixture was filtered and a clear yellow solution of acidic filtrate was obtained. The acidic filtrate was then mixed with sodium carbonate and stirred until it turned to dark grey with pH 11 to become basic filtrate. To separate the alkaloids from the basic crude extract, chloroform was added to mixture in separating funnel. Component of three layers were produced which were the aqueous, salt and chloroform layer. The chloroform layer was then separated and filtered out from the mixture. The chloroform fraction was mixed with sodium sulfate anhydrous and evaporated to yield 0.73% (w/w) of crude extract. The major alkaloid isolated by silica gel chromatography and thin layer chromatography eluting with diethyl ether was identified as MG with standard nuclear magnetic resonance method (1H NMR, 13C NMR). Over all, the yield of MG was approximately 0.087% (w/w) of fresh leaves (Figure 8).


Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system.

Shamima AR, Fakurazi S, Hidayat MT, Hairuszah I, Moklas MA, Arulselvan P - Int J Mol Sci (2012)

Schematic representation of isolation of mitragynine from Mitragyna speciosa.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472755&req=5

f8-ijms-13-11427: Schematic representation of isolation of mitragynine from Mitragyna speciosa.
Mentions: One kilogram leaves of MS was cleaned and dried with constant temperature at 45 °C overnight before grinded into powder form. It was then macerated with absolute methanol for 72 h. The mixture was filtered to remove filtrate from insoluble particles to obtain the methanol extract. Extract was evaporated using rotary evaporator (Eyela, Japan) at a temperature below 55 °C. The methanol extract was added with 5% sulphuric acid and extensively stirred overnight. The mixture was filtered and a clear yellow solution of acidic filtrate was obtained. The acidic filtrate was then mixed with sodium carbonate and stirred until it turned to dark grey with pH 11 to become basic filtrate. To separate the alkaloids from the basic crude extract, chloroform was added to mixture in separating funnel. Component of three layers were produced which were the aqueous, salt and chloroform layer. The chloroform layer was then separated and filtered out from the mixture. The chloroform fraction was mixed with sodium sulfate anhydrous and evaporated to yield 0.73% (w/w) of crude extract. The major alkaloid isolated by silica gel chromatography and thin layer chromatography eluting with diethyl ether was identified as MG with standard nuclear magnetic resonance method (1H NMR, 13C NMR). Over all, the yield of MG was approximately 0.087% (w/w) of fresh leaves (Figure 8).

Bottom Line: Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system.Naloxonazine did inhibit the effect of MG, but it was not statistically significant.These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, Cyberjaya University College of Medical Sciences, 63000 Cyberjaya, Selangor, Malaysia; E-Mail: alfaqirah_msc@yahoo.com.

ABSTRACT
Cannabinoids and opioids systems share numerous pharmacological properties and antinociception is one of them. Previous findings have shown that mitragynine (MG), a major indole alkaloid found in Mitragyna speciosa (MS) can exert its antinociceptive effects through the opioids system. In the present study, the action of MG was investigated as the antinociceptive agent acting on Cannabinoid receptor type 1 (CB1) and effects on the opioids receptor. The latency time was recorded until the mice showed pain responses such as shaking, licking or jumping and the duration of latency was measured for 2 h at every 15 min interval by hot plate analysis. To investigate the beneficial effects of MG as antinociceptive agent, it was administered intraperitoneally 15 min prior to pain induction with a single dosage (3, 10, 15, 30, and 35 mg/kg b.wt). In this investigation, 35 mg/kg of MG showed significant increase in the latency time and this dosage was used in the antagonist receptor study. The treated groups were administered with AM251 (cannabinoid receptor-1 antagonist), naloxone (non-selective opioid antagonist), naltrindole (δ-opioid antagonist) naloxonazine (μ(1)-receptor antagonist) and norbinaltorpimine (κ-opioid antagonist) respectively, prior to administration of MG (35 mg/kg). The results showed that the antinociceptive effect of MG was not antagonized by AM251; naloxone and naltrindole were effectively blocked; and norbinaltorpimine partially blocked the antinociceptive effect of MG. Naloxonazine did inhibit the effect of MG, but it was not statistically significant. These results demonstrate that CB1 does not directly have a role in the antinociceptive action of MG where the effect was observed with the activation of opioid receptor.

Show MeSH
Related in: MedlinePlus