Cyclooxygenase-2 (COX-2) inhibitors: future therapeutic strategies for epilepsy management

Rawat, Chitra; Kukal, Samiksha; Dahiya, Ujjwal Ranjan; Kukreti, Ritushree

doi:10.1186/s12974-019-1592-3

Cited by 113 publications

(94 citation statements)

References 161 publications

(168 reference statements)

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“…In this view, a significant attempt has been made to ameliorate the seizure induction via the implementation of selective COX-2 inhibitors such as celecoxib or aspirin. 8 The result of the present investigation also suggests that the administration of P. amarus attenuated PTZ-induced convulsion and kindling via inhibition of COX-2 and TLR-4 expressions, which is line with findings of the previous researcher. 17 Management of epileptogenesis with the use of herbal therapies provide a ray of hope due to its less side effect as compared to existing antiepileptic drugs (AEDs).…”

Section: Discussionsupporting

confidence: 92%

Phyllathin From Phyllanthus Amarus Ameliorates Epileptic Convulsion and Kindling Associated Post-Ictal Depression in Mice via Inhibition of NF-κB/TLR-4 Pathway

Zhang

Hua

et al. 2020

Dose-Response

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Background: Epilepsy is a chronic, complex, unprovoked, and recurrent disorder of the nervous system that affected several people worldwide. Phyllanthus amarus (PA) has been documented to have neuroprotective potential. Aim: To evaluate the potential of standardized extract of PA and its possible mechanism of action against the Pentylenetetrazol (PTZ)-induced convulsion and kindling associated post-ictal depression in experimental mice. Materials and Methods: Phyllathin was isolated from methanolic extract of PA and well-characterized using HPTLC, ESI-MS/MS, and LC/MS. Phyllathin containing a standardized extract of PA (50, 100, and 200 mg/kg) was administered in convulsed and kindled mice, followed by an assessment of various parameters. Results: The spectral analysis confirmed the molecular formula and weight of phyllanthin as C24H34O6 and 418.2342 Da. PA (100 and 200 mg/kg) significantly ameliorated PTZ-induced ( p < 0.05) duration, onset of tonic-clonic convulsion, and mortality in mice. It also significantly attenuated ( p < 0.05) PTZ-induced kindling in mice. Alteration in brain GABA, dopamine, and glutamate, Na+K+ATPase, Ca+2-ATPase activities, and oxido-nitrosative stress in kindled mice was significantly restored ( p < 0.05) by PA treatment. It also significantly ( p < 0.05) down-regulated brain mRNA expressions of NF-κB, TNF-α, IL-1β, COX-2, and TLR-4. Histological aberrations induced by PTZ in the brain of a kindled rat was significantly ( p < 0.05) ameliorated by PA. Conclusion: Phyllanthin containing a standardized extract of PA exerts its antiepileptic potential via balancing excitatory (glutamate) and inhibitory (GABA) brain monoamines, voltage-gated ion channels (Na+K+/Ca+2-ATPase) and inhibition of NF-κB/TLR-4 pathway to ameliorate neuroinflammation (TNF-α, IL-1β, and COX-2) in experimental mice.

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Section: Discussionsupporting

confidence: 92%

Phyllathin From Phyllanthus Amarus Ameliorates Epileptic Convulsion and Kindling Associated Post-Ictal Depression in Mice via Inhibition of NF-κB/TLR-4 Pathway

Zhang

Hua

et al. 2020

Dose-Response

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“…More than twenty-five cytokines are controlled directly by NF-κB. On the other hand, high levels of TNF-α promptly activates Cox-2 and NF-κB in a positive feedback loop (37). In a study of Walker et al (38) celecoxib has shown a similar Cox-2 selectivity ratio to diclofenac.…”

Section: Discussionmentioning

confidence: 99%

The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation

Gowayed

Abdel-Bary

El-Tahan

2020

Preprint

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Background: Surgical procedures cause perioperative immunosuppression and neuroendocrine stress, exerted by activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. The acetylcholinesterase inhibitor (ACHEI); neostigmine, is known clinically for its analgesic effect in the perioperative phases proving high efficacy; besides possessing anti-inflammatory properties controlling immune cells and cytokine level. Hence, this study evaluated and compared the analgesic and anti-inflammatory activities of the combination of selective Cox-2 inhibitor; celecoxib, with neostigmine versus a combination of the non-selective Cox inhibitor; diclofenac, with neostigmine; in different experimental models of analgesia and inflammation in rats.Methods: Analgesic activity of neostigmine with/without diclofenac or celecoxib was assessed in female Sprague-Dawely rats using the tail clip model and acetic acid induced writhing. Serum level of β-endorphin was assessed after the tail clip test. The anti-inflammatory activity was evaluated using acute and sub-chronic formalin induced paw edema. At the end of the sub-chronic formalin test, blood samples were collected for analysis of anti-inflammatory, liver and kidney function markers. Livers, kidneys and hind paws were also examined histopathologically.Results: Addition of neostigmine to selective or non-selective NSAIDs (celecoxib or diclofenac) causes an increased level of analgesia of NSAIDs with rapid onset of action and short duration, while causing potentiation of the anti-inflammatory effect of neostigmine as seen in the tail clip, writhing, formalin test, Cox-1 and Cox-2 activities, serum β-endorphin, TNF-α, NF-кB and HS-CRP. All combinations of this study disturb some kidney and liver functions, however with normal histopathological appearances, while hind paws reveal improved inflammatory infiltration in all treated groups. Conclusion: Selective and non-selective NSAIDs examined in this study could be good adjunct options to general anesthetic agents and neostigmine in perioperative stages, an outcome that needs further clinical investigations.

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“…More than twenty-ve cytokines are controlled directly by NF-κB. On the other hand, high levels of TNF-α promptly activates Cox-2 and NF-κB in a positive feedback loop (43). In a study of Walker et al (44) celecoxib has shown a similar Cox-2 selectivity ratio to diclofenac.…”

Section: Discussionmentioning

confidence: 99%

The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation

Gowayed

Abdel-Bary

El-Tahan

2020

Preprint

View full text Add to dashboard Cite

Background Surgical procedures cause perioperative immunosuppression and neuroendocrine stress, exerted by activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. The acetylcholinesterase inhibitor (ACHEI); neostigmine, is known clinically for its analgesic effect in the perioperative phases proving high efficacy; besides possessing anti-inflammatory properties controlling immune cells and cytokine level. Hence, this study evaluated and compared the analgesic and anti-inflammatory activities of the combination of selective Cox-2 inhibitor; celecoxib, with neostigmine versus a combination of the non-selective Cox inhibitor; diclofenac, with neostigmine; in different experimental models of analgesia and inflammation in rats. Methods Analgesic activity of neostigmine with/without diclofenac or celecoxib was assessed in female Sprague-Dawely rats using the tail clip model and acetic acid induced writhing. Serum level of β-endorphin was assessed after the tail clip test. The anti-inflammatory activity was evaluated using acute and sub-chronic formalin induced paw edema. At the end of the sub-chronic formalin test, blood samples were collected for analysis of anti-inflammatory, liver and kidney function markers. Livers, kidneys and hind paws were also examined histopathologically. Results Addition of neostigmine to selective or non-selective NSAIDs (celecoxib or diclofenac) causes an increased level of analgesia of NSAIDs with rapid onset of action and short duration, while causing potentiation of the anti-inflammatory effect of neostigmine as seen in the tail clip, writhing, formalin test, Cox-1 and Cox-2 activities, serum β-endorphin, TNF-α, NF-кB and HS-CRP. All combinations of this study disturb some kidney and liver functions, however with normal histopathological appearances, while hind paws reveal improved inflammatory infiltration in all treated groups. Conclusion : Selective and non-selective NSAIDs examined in this study could be good adjunct options to general anesthetic agents and neostigmine in perioperative stages, an outcome that needs further clinical investigation.

show abstract

Cyclooxygenase-2 (COX-2) inhibitors: future therapeutic strategies for epilepsy management

Cited by 113 publications

References 161 publications

Phyllathin From Phyllanthus Amarus Ameliorates Epileptic Convulsion and Kindling Associated Post-Ictal Depression in Mice via Inhibition of NF-κB/TLR-4 Pathway

Phyllathin From Phyllanthus Amarus Ameliorates Epileptic Convulsion and Kindling Associated Post-Ictal Depression in Mice via Inhibition of NF-κB/TLR-4 Pathway

The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation

The effective interplay of (non-) selective NSAIDs with Neostigmine in animal models of analgesia and inflammation

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