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

IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Sheilla da Silva Barroso, Lorenna E. S. Lopes, Ana M. G. dos Santos, Reinaldo V. B. Neto, Bruno dos Santos Lima, Adriano A. de Souza Araújo, Juliana C. Cardoso, Patricia Severino, Eliana B. Souto, Margarete Z. Gomes
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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.

Abstract Image

富含利尿素的巴西红蜂胶水醇提取物可降低3,4-二羟基苯丙氨酸诱导的半帕金森大鼠运动障碍
3,4-二羟基苯丙氨酸(L-DOPA)引起的运动障碍的建立和进展与氧化应激和神经炎症密切相关。本研究旨在研究巴西红蜂胶水醇提取物(HERP)对左旋多巴诱导的半帕金森大鼠运动障碍(LID)的影响。6-羟多巴胺(6-OHDA)注射于内侧前脑束(MFB)。治疗21 d后,测定大鼠脑不自主运动异常(AIM)和自发运动参数,并进行神经胶质纤维酸性蛋白(GFAP)和酪氨酸羟化酶(TH)的免疫组化。HPLC-DAD证实HERP中存在生物茶素A、刺芒柄花素和主要化合物清肾素。HERP在体外表现出较高的抗氧化作用,而在体内,10 mg/kg HERP和40 mg/kg金刚烷胺(AMAN)可抵消左旋多巴的运动、口舌、肢体和轴向运动障碍效应。然而,在行为评估中,单独的HERP并没有降低左旋多巴的抗帕金森作用。免疫染色显示左旋多巴增加GFAP的表达,而HERP和AMAN降低GFAP的表达。HERP降低了同侧TH的表达缺失,而HERP和AMAN增加了对侧中脑TH的表达。HERP诱导大鼠的抗运动障碍作用,运动改善,与标准药物相比,这是一个进步,这些作用可能是由星形胶质细胞相关机制介导的。
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来源期刊
CiteScore
5.60
自引率
6.50%
发文量
126
审稿时长
1 months
期刊介绍: Basic & Clinical Pharmacology and Toxicology is an independent journal, publishing original scientific research in all fields of toxicology, basic and clinical pharmacology. This includes experimental animal pharmacology and toxicology and molecular (-genetic), biochemical and cellular pharmacology and toxicology. It also includes all aspects of clinical pharmacology: pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, drug/drug interactions, pharmacogenetics/-genomics, pharmacoepidemiology, pharmacovigilance, pharmacoeconomics, randomized controlled clinical trials and rational pharmacotherapy. For all compounds used in the studies, the chemical constitution and composition should be known, also for natural compounds.
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