POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
FRIDAY, 5:45-6:30 PM
Park J, Sucher N, Baek NI, White S, Leung PC, Watanabe
K, Eisenberg D, Schachter S.
An international collaboration to develop new therapies
for epilepsy from herbal medicines: preliminary findings.
Division for Research and Education in Complementary
and Integrative Therapies, Harvard Medical School, Osher Institute jongbae_park@hms.harvard.edu
PURPOSE: 1) To address the limitations of the
previous studies of Asian herbal medicines for epilepsy by assembling
an integrated, international team of senior investigators with complementary
methodologies and expertise in authentication; 2) to identify Asian
herbal medicines with potential therapeutic benefit for epilepsy; 3)
test their extracts and compounds in established animal models of epilepsy;
and 4) determine their potential mechanisms of action in vitro.
METHODS: Herbal medicines were selected based
on knowledge and experience of the investigators and literature from
China, Japan and Korea. Prepared extracts and compounds were assessed
in mouse maximal electroshock (MES) and subcutaneous pentylenetetrazole
(ScMET) models (given i.p.), and, as quantities allowed, in rat MES
and ScMET models (i.p. and oral) and the mouse 6-Hz model (i.p.). When
possible, ED50s were calculated for therapeutic and toxic effects on
motor behavior.
RESULTS: To date, 11 herbal medicine extracts
and compounds have been prepared and studied in the animal models. Of
the 5 extracts, 4 showed anticonvulsant activity. In addition, 5 of
the 6 compounds showed anticonvulsant activity. Only 1 compound and
3 extracts were sufficient in quantity to calculate ED50s for therapeutic
effects, and in the 3 extracts, dosages 2- to 8-fold higher than the
therapeutic ED50s were non-toxic in tests of motor behavior (rotarod
test). In vitro studies are in progress. HupA was found to be active
against ScMET, but not MES-induced seizures. Peak anticonvulsant activity
was observed one-hour after oral administration of 1 mg/kg. At the doses
tested (i.e., 1, 2, and 4 mg/kg), a maximum of 62.5% protection was
observed at a non-toxic dose of 1 mg/kg. Behavioral motor impairment
in 75 and 100% of mice tested was observed at doses of 2 and 4 mg/kg,
respectively.
CONCLUSION: HupA is orally bioavailable and
reaches effective brain concentrations in animal models. Given that
HupA is an NMDA receptor antagonist, it may also be effective as neuroprotective
therapy for the prevention of epileptogenesis and seizure-induced neuronal
toxicity. Since the extracts of Asian herbal medicines and extract-derived
compounds studied to date demonstrate promising activity in animal models
of epilepsy, further pre-clinical evaluation, and, when possible, clinical
studies in patients with medically-refractory epilepsy are warranted.
Back