Reply to M. Heidari and S. Rezaei

Dear Editor:

We recently published a Perspective article in the Journal entitled “Therapeutic potential of flavonoids as alternative medicines in epilepsy” (1). Following a comprehensive literature review, we summarized the adverse effects of antiepileptic drugs (AEDs) in patients with epilepsy and assessed the therapeutic properties of natural flavonoids against the neurotoxic events associated with epileptic seizures (1). We described the beneficial effects of natural flavonoids in experimental models of epilepsy. We suggested these compounds as potential antiepileptic agents, particularly for future clinical trials and treatment. Although no clinical trials have been proposed or conducted, we are confident that the Perspective article will build support for testing the therapeutic potential of different flavonoids against epilepsy.

Heidari and Rezaei have conveyed their concerns about the information we presented, with a focus on the comparison between flavonoids and AEDs. According to our literature review (1), many reports have shown that conventional AEDs are accompanied by adverse effects, suggesting a need to develop new, more effective therapeutic methods and drugs to treat epilepsy. We thus described the experimental effects of various flavonoids to promote their potential as alternative medicines. As phytonutrients, natural flavonoids are generally considered safer than conventional drugs.

Rezaei et al. (2) recently published a review describing the short- and long-term efficacy of a ketogenic diet for patients with epilepsy, as well as other treatments. They imply that such therapeutic methods might be used in place of AEDs. We agree with their review and with their Letter to the Editor as to the existence of alternative treatments for epilepsy. In addition to these, we suggest the use of effective flavonoids.

We cannot conclude whether natural flavonoids that show therapeutic potential in animal models of epilepsy are more effective than AEDs in the human brain due to a lack of primary research to date. Our intention in the Perspective article was to suggest the potential viability of natural flavonoids as alternative medicines in epilepsy, as described above (1). In particular, we emphasized the inhibition of granule cell dispersion (GCD) formation in the dentate gyrus as worthy of further study. GCD formation is associated with hippocampal sclerosis in ∼40% of epilepsy patients (1), and inhibition of this formation could be an important mechanism for controlling epileptic seizures. In addition to the inhibition of GCD formation, treatment with various flavonoids was associated with the induction of neuroprotective effects, reduction in inflammatory responses, and control of abnormal neurotransmitter release, as demonstrated in kainic acid–induced animal models of epilepsy (3–8). Circumstances suggest that clinical studies using natural flavonoids should be considered in the near future.

Notes

The authors’ responsibilities were as follows—UJJ and SRK: conceived and designed the Letter to the Editor; SRK: wrote and edited the manuscript; and both authors: contributed to the preparation of the manuscript and read and approved the final manuscript.

This work was supported by a grant from the National Research Foundation of Korea (NRF-2017R1A2B4002675) by the Korean government.

Author disclosures: The authors report no conflicts of interest.