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Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases Fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia.

Nascimento SS, Araújo AA, Brito RG, Serafini MR, Menezes PP, DeSantana JM, Lucca W, Alves PB, Blank AF, Oliveira RC, Oliveira AP, Albuquerque RL, Almeida JR, Quintans LJ - Int J Mol Sci (2014)

Bottom Line: After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein.Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression.Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pre-Clinical Pharmacology (LAPEC), Department of Physiology, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, CEP: 49.000-100, São Cristóvão, Sergipe 49.100-000, Brazil. simonenascimento.saude@gmail.com.

ABSTRACT
O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

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Related in: MedlinePlus

Neurons FOS positive in the periaqueductal grey (A); nucleus raphe magnus (B) and locus coeruleus (C). The animals were treated with vehicle (A; v.o.) LEO (B: 25 mg/kg; v.o.), LEO-β-CD (C: 25, D: 50 and E: 100 mg/kg; v.o.) or TRM (F: 4 mk/kg; i.p.). Values represent in mean ± SEM (n = 8, per group). *p < 0.05, **p < 0.01 and ***p < 0.001 vs. control (one-way ANOVA followed by Bonferroni test).
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ijms-16-00547-f006: Neurons FOS positive in the periaqueductal grey (A); nucleus raphe magnus (B) and locus coeruleus (C). The animals were treated with vehicle (A; v.o.) LEO (B: 25 mg/kg; v.o.), LEO-β-CD (C: 25, D: 50 and E: 100 mg/kg; v.o.) or TRM (F: 4 mk/kg; i.p.). Values represent in mean ± SEM (n = 8, per group). *p < 0.05, **p < 0.01 and ***p < 0.001 vs. control (one-way ANOVA followed by Bonferroni test).

Mentions: The immunofluorescence for Fos protein showed that LEO and LEO/β-CD significantly activated (p < 0.05) neurons at PAG, NRM and LC, when compared with control (vehicle) animals in doses of LEO/β-CD 100 mg/kg, LEO 25 mg/kg and TRM (4 mg/kg) (Figure 6). However, the treatment with LEO and LEO/β-CD, at all doses, did not change the average number of neurons showing Fos protein in the gigantocelullar (GIG) and rostroventromedial medullary (RVM) when compared with control animals (data not shown).


Cyclodextrin-complexed Ocimum basilicum leaves essential oil increases Fos protein expression in the central nervous system and produce an antihyperalgesic effect in animal models for fibromyalgia.

Nascimento SS, Araújo AA, Brito RG, Serafini MR, Menezes PP, DeSantana JM, Lucca W, Alves PB, Blank AF, Oliveira RC, Oliveira AP, Albuquerque RL, Almeida JR, Quintans LJ - Int J Mol Sci (2014)

Neurons FOS positive in the periaqueductal grey (A); nucleus raphe magnus (B) and locus coeruleus (C). The animals were treated with vehicle (A; v.o.) LEO (B: 25 mg/kg; v.o.), LEO-β-CD (C: 25, D: 50 and E: 100 mg/kg; v.o.) or TRM (F: 4 mk/kg; i.p.). Values represent in mean ± SEM (n = 8, per group). *p < 0.05, **p < 0.01 and ***p < 0.001 vs. control (one-way ANOVA followed by Bonferroni test).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307262&req=5

ijms-16-00547-f006: Neurons FOS positive in the periaqueductal grey (A); nucleus raphe magnus (B) and locus coeruleus (C). The animals were treated with vehicle (A; v.o.) LEO (B: 25 mg/kg; v.o.), LEO-β-CD (C: 25, D: 50 and E: 100 mg/kg; v.o.) or TRM (F: 4 mk/kg; i.p.). Values represent in mean ± SEM (n = 8, per group). *p < 0.05, **p < 0.01 and ***p < 0.001 vs. control (one-way ANOVA followed by Bonferroni test).
Mentions: The immunofluorescence for Fos protein showed that LEO and LEO/β-CD significantly activated (p < 0.05) neurons at PAG, NRM and LC, when compared with control (vehicle) animals in doses of LEO/β-CD 100 mg/kg, LEO 25 mg/kg and TRM (4 mg/kg) (Figure 6). However, the treatment with LEO and LEO/β-CD, at all doses, did not change the average number of neurons showing Fos protein in the gigantocelullar (GIG) and rostroventromedial medullary (RVM) when compared with control animals (data not shown).

Bottom Line: After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein.Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression.Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pre-Clinical Pharmacology (LAPEC), Department of Physiology, Federal University of Sergipe, Av. Tancredo Neves, S/N, Rosa Elza, CEP: 49.000-100, São Cristóvão, Sergipe 49.100-000, Brazil. simonenascimento.saude@gmail.com.

ABSTRACT
O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. β-Cyclodextrin (β-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in β-CD (LEO/β-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/β-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-βCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with β-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.

Show MeSH
Related in: MedlinePlus