da Silva Barroso Sheilla, Lopes Lorenna E S, Dos Santos Ana M G, Neto Reinaldo V B, Dos Santos Lima Bruno, de Souza Araújo Adriano A, Cardoso Juliana C, Severino Patricia, Souto Eliana B, Gomes Margarete Z
Tiradentes University (UNIT), Aracaju, Sergipe, Brazil.
Department of Pharmaceutical Sciences, Federal University of Sergipe (UFS), São Cristóvão, Sergipe, Brazil.
Basic Clin Pharmacol Toxicol. 2025 Jul;137(1):e70062. doi: 10.1111/bcpt.70062.
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.
3,4-二羟基苯丙氨酸(L-多巴)诱发的运动障碍的发生和进展与氧化应激和神经炎症密切相关。本研究旨在探讨和表征巴西红蜂胶水醇提取物(HERP)对向内侧前脑束(MFB)注射6-羟基多巴胺(6-OHDA)的偏侧帕金森病大鼠L-多巴诱发的运动障碍(LID)的影响。在21天的治疗过程中评估异常不自主运动(AIM)和自发运动参数,然后对大鼠脑进行胶质纤维酸性蛋白(GFAP)和酪氨酸羟化酶(TH)的免疫组织化学检测。通过HPLC-DAD证实了HERP中存在生物chanin A、芒柄花素和主要化合物甘草素。HERP在体外具有高抗氧化作用,而在体内,10mg/kg的HERP和40mg/kg的金刚烷胺(AMAN)可抵消L-多巴的运动、口面部、肢体和轴向运动障碍作用。然而,单独使用HERP在行为评估中并未降低L-多巴的抗帕金森病作用。免疫染色显示,L-多巴增加了GFAP表达,而HERP和AMAN可使其降低。HERP减少了同侧TH表达的缺失,而HERP和AMAN增加了中脑TH的对侧表达。HERP在大鼠中诱导了抗运动障碍作用,伴有运动改善,这相较于标准药物是一个进步,且这些作用可能由星形胶质细胞相关机制介导。