Goncalves Valeria C, Silva da Fonsêca Victor, de Paula Faria Daniele, Izidoro Mario Augusto, Berretta Andresa Aparecida, de Almeida Antônio-Carlos G, Affonso Fonseca Fernando Luiz, Scorza Fulvio Alexandre, Scorza Carla Alessandra
Disciplina de Neurociência, Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Laboratory of Nuclear Medicine (LIM43), Department of Radiology and Oncology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, Brazil.
Front Pharmacol. 2022 Oct 13;13:1013703. doi: 10.3389/fphar.2022.1013703. eCollection 2022.
While there is sustained growth of the older population worldwide, ageing is a consistent risk factor for neurodegenerative diseases, such as Parkinson's-disease (PD). Considered an emblematic movement disorder, PD comprises a miscellany of non-motor symptoms, for which effective management remains an unfulfilled need in clinical practice. Highlighted are the cardiovascular abnormalities, that cause significant burden in PD patients. Evidence suggests that key biological processes underlying PD pathophysiology can be modulated by diet-derived bioactive compounds, such as green propolis, a natural functional food with biological and pharmacological properties. The effects of propolis on cardiac affection associated to PD have received little coverage. In this study, a metabolomics approach and Positron Emission Tomography (PET) imaging were used to assess the metabolic response to diet supplementation with green propolis on heart outcomes of rats with Parkinsonism induced by 6-hydroxydopamine (6-OHDA rats). Untargeted metabolomics approach revealed four cardiac metabolites (2-hydroxybutyric acid, 3-hydroxybutyric acid, monoacylglycerol and alanine) that were significantly modified between animal groups (6-OHDA, 6-OHDA + Propolis and sham). Propolis-induced changes in the level of these cardiac metabolites suggest beneficial effects of diet intervention. From the metabolites affected, functional analysis identified changes in propanoate metabolism (a key carbohydrate metabolism related metabolic pathway), glucose-alanine cycle, protein and fatty acid biosynthesis, energy metabolism, glutathione metabolism and urea cycle. PET imaging detected higher glucose metabolism in the 17 areas of the left ventricle of all rats treated with propolis, substantially contrasting from those rats that did not consume propolis. Our results bring new insights into cardiac metabolic substrates and pathways involved in the mechanisms of the effects of propolis in experimental PD and provide potential novel targets for research in the quest for future therapeutic strategies.
虽然全球老年人口持续增长，但老龄化是神经退行性疾病（如帕金森病（PD））的一个持续风险因素。PD被认为是一种典型的运动障碍，它包含一系列非运动症状，在临床实践中，对这些症状的有效管理仍是未满足的需求。突出的是心血管异常，这给PD患者带来了重大负担。有证据表明，PD病理生理学的关键生物学过程可被饮食来源的生物活性化合物调节，如绿色蜂胶，这是一种具有生物学和药理学特性的天然功能食品。蜂胶对与PD相关的心脏影响的作用鲜少被报道。在本研究中，采用代谢组学方法和正电子发射断层扫描（PET）成像来评估用绿色蜂胶进行饮食补充对6-羟基多巴胺诱导的帕金森病大鼠（6-OHDA大鼠）心脏结局的代谢反应。非靶向代谢组学方法揭示了四种心脏代谢物（2-羟基丁酸、3-羟基丁酸、单酰甘油和丙氨酸）在动物组（6-OHDA、6-OHDA + 蜂胶和假手术组）之间有显著变化。蜂胶引起的这些心脏代谢物水平变化表明饮食干预具有有益作用。从受影响的代谢物中，功能分析确定了丙酸代谢（一种与碳水化合物代谢相关的关键代谢途径）、葡萄糖-丙氨酸循环、蛋白质和脂肪酸生物合成、能量代谢、谷胱甘肽代谢和尿素循环的变化。PET成像检测到所有接受蜂胶治疗的大鼠左心室17个区域的葡萄糖代谢更高，这与未食用蜂胶的大鼠形成了显著对比。我们的结果为参与蜂胶在实验性PD作用机制的心脏代谢底物和途径带来了新见解，并为寻求未来治疗策略的研究提供了潜在的新靶点。
