Abstract

Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs) are available but have tolerability issues due to their side effects. The Malaysian herb Orthosiphon stamineus, is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract of O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures in a zebrafish model; and the effects of the extract on the expression levels of several genes in the zebrafish brain which are associated with seizures. The results of this study indicate that O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures as it is pharmacologically active against seizures in a zebrafish model. The anti-convulsive effect of this extract is also comparable to that of diazepam at higher doses and can surpass diazepam in certain cases. Treatment with the extract also counteracts the upregulation of NF-κB, NPY and TNF-α as a result of a Pentylenetetrazol (PTZ) treated seizure. The anti-convulsive action for this extract could be at least partially due to its downregulation of TNF-α. Future work could include the discovery of the active anti-convulsive compound, as well as determine if the extract does not cause cognitive impairment in zebrafish.

Highlights

  • Epileptic seizures are typically described as a short-term manifestation of numerous signs and/or symptoms because of unusually superfluous or concurrent activity in the brain

  • Epilepsy is a serious disorder of the Central Nervous System (CNS) as the global epilepsy prevalence is approximately one in 100 people according to Holland (2014)

  • As oxidative stress plays a role in epilepsy (Devi et al, 2008) and that the phenols in O. stamineus such as rosmarinic acid possess significant free radical scavenging, anti-inflammatory and antioxidant ability (Akowuah et al, 2005; Yam et al, 2010), an ethanolic extract of O. stamineus is the ideal choice for this experiment

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Summary

Introduction

Epileptic seizures are typically described as a short-term manifestation of numerous signs and/or symptoms because of unusually superfluous or concurrent activity in the brain. Epilepsy is a collection of neurological disorders characterized by the lasting tendency to spawn epileptic seizures (Fisher et al, 2014). Epilepsy is a serious disorder of the Central Nervous System (CNS) as the global epilepsy prevalence is approximately one in 100 people according to Holland (2014). Whilst the underlying cause of epilepsy is not always clear, anti-convulsant drugs or antiepileptic drugs (AEDs) as they are commonly known, may be used for the symptomatic treatment of epilepsy. The older generation of AEDs have side effects which range from abdominal discomfort and anorexia to psychosis and aplastic anemia; together with an array of different idiosyncratic reactions. AEDs from the newer generation can result in side effects which range from fatigue and drowsiness to vomiting and diplopia (French and Gazzola, 2011). Whilst the efficacy of the AEDs in use today has been demonstrated, a need for the discovery of new AEDs with fewer side effects remains

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