Ferulic Acid Inhibits Catamenial Epilepsy Through Modulation of Female Hormones

Abstract Approximately 40% of women with epilepsy experience perimenstrual seizure exacerbation, referred to as catamenial epilepsy. These seizures result from cyclic changes in circulating progesterone and estradiol levels and there is no effective treatment for this form of intractable epilepsy. We artificially increased progesterone levels and neurosteroid levels (pseudo-pregnancy) in adult Swiss albino female mice (19-23 g) by injecting them with pregnant mares' serum gonadotropin (5 IU s.c.), followed by human chorionic gonadotropin (5 IU s.c.) after 46 hours. After this, ferulic acid (25, 50, 100 mg/kg i.p.) treatment was observed for 10 days. During treatment, progesterone, estradiol, and corticosterone levels were estimated in blood on days 1, 5, and 10. Neurosteroid withdrawal was induced by finasteride (50 mg/kg, i.p.), a 5 α-reductase inhibitor on treatment day 9. Twenty-four hours after finasteride administration (day 10 of treatment), seizure susceptibility was evaluated with the sub-convulsant pentylenetetrazol (PTZ) dose (40 mg/kg i.p.). Four to six hours after PTZ, animals were assessed for depression like phenotypes using tail-suspension test (TST). Four to six hours following TST, animals were euthanized, and discrete brain parts (cortex and hippocampus) were separated for estimation of norepinephrine, serotonin, and dopamine as well as glutamic acid decarboxylase enzyme activity. PMSG and HCG treatment elevated progesterone and estradiol levels, assessed on days 1, 5, and 10 causing a state of pseudo-pregnancy. Treatment with finasteride increases seizure susceptibility and depression-like characteristics possibly due to decreased progesterone levels and elevated estrogen levels coupled with decreased monoamine and elevated corticosterone levels. Ferulic acid treatment, on the other hand, significantly decreased seizure susceptibility and depression like behaviours, possibly as a result of increased progesterone, restored estradiol, corticosterone, monoamine, and glutamic acid decarboxylase enzyme activity. We concluded that ferulic acid exhibited antiepileptic effects in a mouse model of catamenial epilepsy and comorbid depression due to its restorative effects on circulating hormones and cerebral monoamine and glutamic acid decarboxylase enzyme activity.