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Chenopodium ambrosioides L. Reduces Synovial Inflammation and Pain in Experimental Osteoarthritis.

Calado GP, Lopes AJ, Costa Junior LM, Lima Fd, Silva LA, Pereira WS, Amaral FM, Garcia JB, Cartágenes Mdo S, Nascimento FR - PLoS ONE (2015)

Bottom Line: After the third day, HCE reduced knee edema.C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain.This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.

View Article: PubMed Central - PubMed

Affiliation: Health Sciences Graduate Program, Federal University of Maranhao, Biologic and Health Sciences Center, Av. dos Portugueses 1966, São Luís, MA, CEP:65085-580, Brazil.

ABSTRACT
The chronicity of osteoarthritis (OA), characterized by pain and inflammation in the joints, is linked to a glutamate receptor, N-methyl-D-aspartate (NMDA). The use of plant species such as Chenopodium ambrosioides L. (Amaranthaceae) as NMDA antagonists offers a promising perspective. This work aims to analyze the antinociceptive and anti-inflammatory responses of the crude hydroalcoholic extract (HCE) of C. ambrosioides leaves in an experimental OA model. Wistar rats were separated into six groups (n = 24): clean (C), negative control (CTL-), positive control (CTL+), HCE0.5, HCE5 and HCE50. The first group received no intervention. The other groups received an intra-articular injection of sodium monoiodoacetate (MIA) (8 mg/kg) on day 0. After six hours, they were orally treated with saline, Maxicam plus (meloxicam + chondroitin sulfate) and HCE at doses of 0.5 mg/kg, 5 mg/kg and 50 mg/kg, respectively. After three, seven and ten days, clinical evaluations were performed (knee diameter, mechanical allodynia, mechanical hyperalgesia and motor activity). On the tenth day, after euthanasia, synovial fluid and draining lymph node were collected for cellular quantification, and cartilage was collected for histopathological analysis. Finally, molecular docking was performed to evaluate the compatibility of ascaridole, a monoterpene found in HCE, with the NMDA receptor. After the third day, HCE reduced knee edema. HCE5 showed less cellular infiltrate in the cartilage and synovium and lower intensities of allodynia from the third day and of hyperalgesia from the seventh day up to the last treatment day. The HCE5 and HCE50 groups improved in forced walking. In relation to molecular docking, ascaridole showed NMDA receptor binding affinity. C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain. This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.

No MeSH data available.


Related in: MedlinePlus

Three-dimensional image of the molecular docking of the interaction of ascaridole with chains A and B of the NMDA receptor.A shows chain A with ascaridole bound to the receptor; the terpene is represented in brown (red circle) in surface mode. B shows chain B with ascaridole bound to the receptor; the terpene is represented in its normal conformation (red circle). C shows the B chain with ascaridole bound to the receptor; the terpene is represented in green (red circle) in a different viewing mode (surface).
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pone.0141886.g005: Three-dimensional image of the molecular docking of the interaction of ascaridole with chains A and B of the NMDA receptor.A shows chain A with ascaridole bound to the receptor; the terpene is represented in brown (red circle) in surface mode. B shows chain B with ascaridole bound to the receptor; the terpene is represented in its normal conformation (red circle). C shows the B chain with ascaridole bound to the receptor; the terpene is represented in green (red circle) in a different viewing mode (surface).

Mentions: In silico analysis indicated that ascaridole can bond to both chain A (Fig 5A) and chain B (Fig 5B and 5C) of the glutamatergic receptor, both containing NMDA receptors. The ascaridole interaction at the active site of NMDA chains A and B featured negative binding energies (-5.19 kcal mol-1for chain A and -5.36 kcal mol-1 for chain B) (Fig 6). Hydrogen bonds (black dashed lines) and hydrophobic interactions were observed.


Chenopodium ambrosioides L. Reduces Synovial Inflammation and Pain in Experimental Osteoarthritis.

Calado GP, Lopes AJ, Costa Junior LM, Lima Fd, Silva LA, Pereira WS, Amaral FM, Garcia JB, Cartágenes Mdo S, Nascimento FR - PLoS ONE (2015)

Three-dimensional image of the molecular docking of the interaction of ascaridole with chains A and B of the NMDA receptor.A shows chain A with ascaridole bound to the receptor; the terpene is represented in brown (red circle) in surface mode. B shows chain B with ascaridole bound to the receptor; the terpene is represented in its normal conformation (red circle). C shows the B chain with ascaridole bound to the receptor; the terpene is represented in green (red circle) in a different viewing mode (surface).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4629912&req=5

pone.0141886.g005: Three-dimensional image of the molecular docking of the interaction of ascaridole with chains A and B of the NMDA receptor.A shows chain A with ascaridole bound to the receptor; the terpene is represented in brown (red circle) in surface mode. B shows chain B with ascaridole bound to the receptor; the terpene is represented in its normal conformation (red circle). C shows the B chain with ascaridole bound to the receptor; the terpene is represented in green (red circle) in a different viewing mode (surface).
Mentions: In silico analysis indicated that ascaridole can bond to both chain A (Fig 5A) and chain B (Fig 5B and 5C) of the glutamatergic receptor, both containing NMDA receptors. The ascaridole interaction at the active site of NMDA chains A and B featured negative binding energies (-5.19 kcal mol-1for chain A and -5.36 kcal mol-1 for chain B) (Fig 6). Hydrogen bonds (black dashed lines) and hydrophobic interactions were observed.

Bottom Line: After the third day, HCE reduced knee edema.C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain.This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.

View Article: PubMed Central - PubMed

Affiliation: Health Sciences Graduate Program, Federal University of Maranhao, Biologic and Health Sciences Center, Av. dos Portugueses 1966, São Luís, MA, CEP:65085-580, Brazil.

ABSTRACT
The chronicity of osteoarthritis (OA), characterized by pain and inflammation in the joints, is linked to a glutamate receptor, N-methyl-D-aspartate (NMDA). The use of plant species such as Chenopodium ambrosioides L. (Amaranthaceae) as NMDA antagonists offers a promising perspective. This work aims to analyze the antinociceptive and anti-inflammatory responses of the crude hydroalcoholic extract (HCE) of C. ambrosioides leaves in an experimental OA model. Wistar rats were separated into six groups (n = 24): clean (C), negative control (CTL-), positive control (CTL+), HCE0.5, HCE5 and HCE50. The first group received no intervention. The other groups received an intra-articular injection of sodium monoiodoacetate (MIA) (8 mg/kg) on day 0. After six hours, they were orally treated with saline, Maxicam plus (meloxicam + chondroitin sulfate) and HCE at doses of 0.5 mg/kg, 5 mg/kg and 50 mg/kg, respectively. After three, seven and ten days, clinical evaluations were performed (knee diameter, mechanical allodynia, mechanical hyperalgesia and motor activity). On the tenth day, after euthanasia, synovial fluid and draining lymph node were collected for cellular quantification, and cartilage was collected for histopathological analysis. Finally, molecular docking was performed to evaluate the compatibility of ascaridole, a monoterpene found in HCE, with the NMDA receptor. After the third day, HCE reduced knee edema. HCE5 showed less cellular infiltrate in the cartilage and synovium and lower intensities of allodynia from the third day and of hyperalgesia from the seventh day up to the last treatment day. The HCE5 and HCE50 groups improved in forced walking. In relation to molecular docking, ascaridole showed NMDA receptor binding affinity. C. ambrosioides HCE was effective in the treatment of OA because it reduced synovial inflammation and behavioral changes due to pain. This effect may be related to the antagonistic effect of ascaridole on the NMDA receptor.

No MeSH data available.


Related in: MedlinePlus