Limits...
Strong and Long-Lasting Antinociceptive and Anti-inflammatory Conjugate of Naturally Occurring Oleanolic Acid and Aspirin.

Bednarczyk-Cwynar B, Wachowiak N, Szulc M, Kamińska E, Bogacz A, Bartkowiak-Wieczorek J, Zaprutko L, Mikolajczak PL - Front Pharmacol (2016)

Bottom Line: After its combined administration with morphine (MF, 5.0 mg/kg, s.c.) the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c.) did not affect the antinociceptive effect of OAO-ASA (8), therefore its opioid mechanism of action should be rather excluded.Moreover, compound 8 did not change unequivocally mRNA TLR1, and TLR3 expression.Concluding, the obtained results regarding the antinociceptive and anti-inflammatory activity of new conjugate of oleanolic acid oxime and acetylsalicylic acid (OAO-ASA 8) are very interesting, but for explanation of its mechanism of action, more detailed studies are necessary.

View Article: PubMed Central - PubMed

Affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences Poznan, Poland.

ABSTRACT
The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7) and aspirin in dioxane. Analgesic effect of OAO-ASA (8) for the range of doses 0.3-300.0 mg/kg (p.o.) was performed in mice using a hot-plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8) did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30.0 mg/kg. After its combined administration with morphine (MF, 5.0 mg/kg, s.c.) the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c.) did not affect the antinociceptive effect of OAO-ASA (8), therefore its opioid mechanism of action should be rather excluded. After combined administration with acetylsalicylic acid (ASA, 300.0 mg/kg, p.o.) in hot-plate test, the examined compound 8 enhanced the antinociceptive activity in significant way. It also shows that rather the whole molecule is responsible for the antinociceptive and anti-inflammatory effect of the tested compound 8, however, it cannot be excluded that the summarizing effect is produced by ASA released from the compound 8 and the rest of triterpene derivative. The occurrence of tolerance for triterpenic derivative 8 was not observed, since the analgesic and anti-inflammatory effects after chronic administration of the conjugate OAO-ASA (8) was on the same level as after its single treatment. It seemed that the anti-inflammatory mechanism of action of OAO-ASA (8) is not simple, even its chronic administration lowered both blood concentration of IL-6 and mRNA IL-6 expression. However, the effects of the conjugate OAO-ASA (8) on TNF-α level and mRNA expression were opposite. Moreover, compound 8 did not change unequivocally mRNA TLR1, and TLR3 expression. Concluding, the obtained results regarding the antinociceptive and anti-inflammatory activity of new conjugate of oleanolic acid oxime and acetylsalicylic acid (OAO-ASA 8) are very interesting, but for explanation of its mechanism of action, more detailed studies are necessary.

No MeSH data available.


Related in: MedlinePlus

Dose-dependent effect of OAO-ASA (8) on horizontal locomotor activity in mice. Number of mice = 9–10 in each group, data are mean ± SEM, control = mice treated with 5% Tween 80, ∗ = vs. Control, p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4940421&req=5

Figure 1: Dose-dependent effect of OAO-ASA (8) on horizontal locomotor activity in mice. Number of mice = 9–10 in each group, data are mean ± SEM, control = mice treated with 5% Tween 80, ∗ = vs. Control, p < 0.05.

Mentions: The study was performed using five groups of mice (n = 9–10 in each group) treated with OAO-ASA (8) in doses of 0.3, 3.0, 30.0, and 300.0 mg/kg (p.o.) and control (5% Tween 80). One-way ANOVA analysis of variance has presented that single administration of the compound 8 in the above range of doses has not shown a statistically significant effect on horizontal locomotor activity in mice [F(4,56) = 3.90; p = 0.007]. The impact of the individual doses of OAO-ASA (8) on horizontal locomotor activity revealed that only a dose of 3.0 mg/kg has increased mobility of the animals during horizontal activity test (p < 0.05). In addition, a decrease in activity was observed after administration of 300.0 mg/kg of this compound 8, but the average value obtained was not significantly different compared to the control values (p > 0.05; Figure 1).


Strong and Long-Lasting Antinociceptive and Anti-inflammatory Conjugate of Naturally Occurring Oleanolic Acid and Aspirin.

Bednarczyk-Cwynar B, Wachowiak N, Szulc M, Kamińska E, Bogacz A, Bartkowiak-Wieczorek J, Zaprutko L, Mikolajczak PL - Front Pharmacol (2016)

Dose-dependent effect of OAO-ASA (8) on horizontal locomotor activity in mice. Number of mice = 9–10 in each group, data are mean ± SEM, control = mice treated with 5% Tween 80, ∗ = vs. Control, p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940421&req=5

Figure 1: Dose-dependent effect of OAO-ASA (8) on horizontal locomotor activity in mice. Number of mice = 9–10 in each group, data are mean ± SEM, control = mice treated with 5% Tween 80, ∗ = vs. Control, p < 0.05.
Mentions: The study was performed using five groups of mice (n = 9–10 in each group) treated with OAO-ASA (8) in doses of 0.3, 3.0, 30.0, and 300.0 mg/kg (p.o.) and control (5% Tween 80). One-way ANOVA analysis of variance has presented that single administration of the compound 8 in the above range of doses has not shown a statistically significant effect on horizontal locomotor activity in mice [F(4,56) = 3.90; p = 0.007]. The impact of the individual doses of OAO-ASA (8) on horizontal locomotor activity revealed that only a dose of 3.0 mg/kg has increased mobility of the animals during horizontal activity test (p < 0.05). In addition, a decrease in activity was observed after administration of 300.0 mg/kg of this compound 8, but the average value obtained was not significantly different compared to the control values (p > 0.05; Figure 1).

Bottom Line: After its combined administration with morphine (MF, 5.0 mg/kg, s.c.) the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c.) did not affect the antinociceptive effect of OAO-ASA (8), therefore its opioid mechanism of action should be rather excluded.Moreover, compound 8 did not change unequivocally mRNA TLR1, and TLR3 expression.Concluding, the obtained results regarding the antinociceptive and anti-inflammatory activity of new conjugate of oleanolic acid oxime and acetylsalicylic acid (OAO-ASA 8) are very interesting, but for explanation of its mechanism of action, more detailed studies are necessary.

View Article: PubMed Central - PubMed

Affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences Poznan, Poland.

ABSTRACT
The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7) and aspirin in dioxane. Analgesic effect of OAO-ASA (8) for the range of doses 0.3-300.0 mg/kg (p.o.) was performed in mice using a hot-plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8) did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30.0 mg/kg. After its combined administration with morphine (MF, 5.0 mg/kg, s.c.) the lowering of antinociceptive activity was found; however, the interaction with naloxone (NL, 3.0 mg/kg, s.c.) did not affect the antinociceptive effect of OAO-ASA (8), therefore its opioid mechanism of action should be rather excluded. After combined administration with acetylsalicylic acid (ASA, 300.0 mg/kg, p.o.) in hot-plate test, the examined compound 8 enhanced the antinociceptive activity in significant way. It also shows that rather the whole molecule is responsible for the antinociceptive and anti-inflammatory effect of the tested compound 8, however, it cannot be excluded that the summarizing effect is produced by ASA released from the compound 8 and the rest of triterpene derivative. The occurrence of tolerance for triterpenic derivative 8 was not observed, since the analgesic and anti-inflammatory effects after chronic administration of the conjugate OAO-ASA (8) was on the same level as after its single treatment. It seemed that the anti-inflammatory mechanism of action of OAO-ASA (8) is not simple, even its chronic administration lowered both blood concentration of IL-6 and mRNA IL-6 expression. However, the effects of the conjugate OAO-ASA (8) on TNF-α level and mRNA expression were opposite. Moreover, compound 8 did not change unequivocally mRNA TLR1, and TLR3 expression. Concluding, the obtained results regarding the antinociceptive and anti-inflammatory activity of new conjugate of oleanolic acid oxime and acetylsalicylic acid (OAO-ASA 8) are very interesting, but for explanation of its mechanism of action, more detailed studies are necessary.

No MeSH data available.


Related in: MedlinePlus