Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures

Abstract

Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile. β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity. In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects. In addition, we investigated the effect of β-caryophyllene on behavioral parameters and on seizure-induced oxidative stress. Adult C57BL/6 mice received increasing doses of β-caryophyllene (0, 10, 30, or 100mg/kg). After 60 min, we measured the latencies to myoclonic and generalized seizures induced by pentylenetetrazole (PTZ, 60 mg/kg). We found that β-caryophyllene increased the latency to myoclonic jerks induced by PTZ. This result was confirmed by electroencephalographic analysis. In a separate set of experiments, we found that mice treated with an anticonvulsant dose of β-caryophyllene (100mg/kg) displayed an improved recognition index in the object recognition test. This effect was not accompanied by behavioral changes in the open-field, rotarod, or forced swim tests. Administration of an anticonvulsant dose of β-caryophyllene (100mg/kg) did not prevent PTZ-induced oxidative stress (i.e., increase in the levels of thiobarbituric acid-reactive substances or the decrease in nonprotein thiols content). Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice. Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.

(−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis

“…Agonism of CB1 and CB2 receptors by exogenous ligands or endocannabinoids in animal models of MS have demonstrated suppression of pro-inflammatory mediators [38], as well as induction of neuroprotection and immunomodulation [39,40,41,42]. BCP (Figure 1), a dietary functional non-psychoactive CB2 receptor ligand [12,13,14] showed analgesic, anti-inflammatory, anticonvulsant, and neuroprotective effects [15,27,29,43,44,45,46]. Nonetheless, the effects of BCP on immune inflammatory diseases of the CNS, such as MS, have not yet been reported.…”

Variation in Essential Oil Yield and Composition of Dorema aucheri Boiss., an Endemic Medicinal Plant Collected from Wild Populations in Natural Habitats

“…aucheri are a valuable source of sequiterpenes such as β ‐caryophyllene, caryophellene oxide and cuparene ( Table ). β ‐caryophyllene is a natural bicyclic sesquiterpene with many biological activities such as neuroprotective, anticancer, antioxidant and antimicrobial, anticonvulsant, anti‐inflammatory activity…”

Reduced cannabinoid 2 receptor activity increases susceptibility to induced seizures in mice

“…[29][30][31][32][33] Although some studies reported that the CB2R agonist beta caryophyllene can be seizure-protective, 29,30 other studies observed either no effect of a CB2R agonist (HU308), 32 or greater seizure severity following administration of the CB2R agonist AM1241. [29][30][31][32][33] Although some studies reported that the CB2R agonist beta caryophyllene can be seizure-protective, 29,30 other studies observed either no effect of a CB2R agonist (HU308), 32 or greater seizure severity following administration of the CB2R agonist AM1241.…”

“…[19][20][21][22] Although the cell-specific pattern of CB2R expression in the brain remains controversial, both microglial and neuronal expression have been described. Systemic administration of the CB2R agonist, beta caryophyllene, was shown to protect against acutely induced seizures in mice 29,30 ; however, another study reported that direct brain injection of the CB2R agonist, AM1241, increased seizure severity in rats. 28 The few studies that have directly examined the effect of modulating CB2R activity on seizure susceptibility have yielded inconsistent results.…”

“…28 The few studies that have directly examined the effect of modulating CB2R activity on seizure susceptibility have yielded inconsistent results. Systemic administration of the CB2R agonist, beta caryophyllene, was shown to protect against acutely induced seizures in mice 29,30 ; however, another study reported that direct brain injection of the CB2R agonist, AM1241, increased seizure severity in rats. 31 Additionally, the CB2R agonist HU-308 had no effect on pentylenetetrazole (PTZ)-induced seizures in young rats.…”