Liquiritigenin-Rich Hydroalcoholic Extract of Brazilian Red Propolis Reduces Dyskinesia Induced by 3,4- Dihydroxyphenylalanine in Hemiparkinsonian Rats

Abstract

The set-up and progression of dyskinesia induced by 3,4-dihydroxyphenylalanine (L-DOPA) are strongly linked to oxidative stress and neuroinflammation. The aim of this work was to study and characterize the effects of the hydroalcoholic extract of Brazilian red propolis (HERP) on L-DOPA–induced dyskinesia (LID) in hemiparkinsonian rats injected with 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). The abnormal involuntary movements (AIM) and spontaneous motor parameters were evaluated over 21 days of treatment, and then immunohistochemistry for glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH) was performed on rat brains. The presence of biochanin A, formononetin and the major compound liquiritigenin in HERP was confirmed by HPLC-DAD. HERP presented a high antioxidant effect in vitro, while in vivo the locomotive, orolingual, limb and axial dyskinetic effects of L-DOPA were counteracted with 10 mg/kg of HERP and 40 mg/kg of amantadine (AMAN). However, HERP alone did not reduce antiparkinsonian effects of L-DOPA in behavioural assessment. Immunostaining showed that L-DOPA increased GFAP expression, which was decreased by HERP and AMAN. HERP decreased the ipsilateral loss of TH expression, whereas HERP and AMAN increased contralateral expression of TH at the mesencephalon. HERP induced antidyskinetic effects in rats, with motor improvement, which is an advancement in comparison to standard medications, and these effects may be mediated by astrocyte-related mechanisms.