Cannabidiol Anticonvulsant Effects Against Lithium-Pilocarpine-Induced Status Epilepticus in Male Rats Are Mediated by Neuroinflammation Modulation and Cannabinoids 1 (CB1), But Not CB2 and GABA<sub>A</sub> Receptors

Masoumi, Mahla; Manavi, Mohammad Amin; Mohammad Jafari, Razieh; Mirzaei, Alireza; Hedayatyanfard, Keshvad; Beigmohammadi, Mohammad Taghi; Dehpour, Ahmad Reza

doi:10.1089/can.2023.0067

Cannabis and Cannabinoid Research

2024

DOI: 10.1089/can.2023.0067

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Cannabidiol Anticonvulsant Effects Against Lithium-Pilocarpine-Induced Status Epilepticus in Male Rats Are Mediated by Neuroinflammation Modulation and Cannabinoids 1 (CB1), But Not CB2 and GABA_A Receptors

Mahla Masoumi,

Mohammad Amin Manavi,

Razieh Mohammad Jafari

et al.

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2024

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Cited by 3 publications

References 90 publications

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Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF

Jouyban,

Mohammad Jafari,

Charkhpour

et al. 2024

Aesth Plast Surg

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Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF

Jouyban,

Mohammad Jafari,

Charkhpour

et al. 2024

Aesth Plast Surg

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Update on Cannabidiol in Drug-Resistant Epilepsy

Singh,

Madaan,

Bansal

2024

Indian J Pediatr

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Plumbagin, a novel TRPV2 inhibitor, ameliorates microglia activation and brain injury in a middle cerebral artery occlusion/reperfusion mouse model

Ding,

Han,

Xie

et al. 2024

British J Pharmacology

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Background and PurposeTransient receptor potential vanilloid 2 (TRPV2) is a Ca2+‐permeable non‐selective cation channel. Despite the significant roles of TRPV2 in immunological response, cancer progression and cardiac development, pharmacological probes of TRPV2 remain to be identified. We aimed to discover TRPV2 inhibitors and to elucidate their molecular mechanism of action.Experimental ApproachFluorescence‐based Ca2+ assay in HEK‐293 cells expressing murine TRPV2 was used to identify plumbagin as a novel TRPV2 inhibitor. Patch‐clamp, in silico docking and site‐directed mutagenesis were applied to investigate the molecular mechanisms critical for plumbagin interaction. ELISA and qPCR were used to assess nitric oxide release and mRNA levels of inflammatory mediators, respectively. si‐RNA interference was used to knock down TRPV2 expression, which was validated by western blotting. Neurological and histological analyses were used to examine brain injury of mice following middle cerebral artery occlusion/reperfusion (MCAO/R).Key ResultsPlumbagin is a potent TRPV2 negative allosteric modulator with an IC50 value of 0.85 μM, exhibiting >14‐fold selectivity over TRPV1, TRPV3 and TRPV4. Plumbagin suppresses TRPV2 activity by decreasing the channel open probability without affecting the unitary conductance. Moreover, plumbagin binds to an extracellular pocket formed by the pore helix and flexible loop between transmembrane helices S5 and S6 of TRPV2. Plumbagin effectively suppresses LPS‐induced inflammation of BV‐2 microglia and ameliorates brain injury of MCAO/R mice.Conclusion and ImplicationsPlumbagin is a novel pharmacological probe to study TRPV2 pathophysiology. TRPV2 is a novel molecular target for the treatment of neuroinflammation and ischemic stroke.

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Cannabidiol Anticonvulsant Effects Against Lithium-Pilocarpine-Induced Status Epilepticus in Male Rats Are Mediated by Neuroinflammation Modulation and Cannabinoids 1 (CB1), But Not CB2 and GABA_A Receptors

Cited by 3 publications

References 90 publications

Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF

Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF

Update on Cannabidiol in Drug-Resistant Epilepsy

Plumbagin, a novel TRPV2 inhibitor, ameliorates microglia activation and brain injury in a middle cerebral artery occlusion/reperfusion mouse model

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Product

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Cannabidiol Anticonvulsant Effects Against Lithium-Pilocarpine-Induced Status Epilepticus in Male Rats Are Mediated by Neuroinflammation Modulation and Cannabinoids 1 (CB1), But Not CB2 and GABAA Receptors

Cited by 3 publications

References 90 publications

Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF

Spermidine Exerts Protective Effects in Random-Pattern Skin Flap Survival in Rats: Possible Involvement of Inflammatory Cytokines, Nitric Oxide, and VEGF

Update on Cannabidiol in Drug-Resistant Epilepsy

Plumbagin, a novel TRPV2 inhibitor, ameliorates microglia activation and brain injury in a middle cerebral artery occlusion/reperfusion mouse model

Contact Info

Product

Resources

About

Cannabidiol Anticonvulsant Effects Against Lithium-Pilocarpine-Induced Status Epilepticus in Male Rats Are Mediated by Neuroinflammation Modulation and Cannabinoids 1 (CB1), But Not CB2 and GABA_A Receptors