Alves Maíra Bernardes, Vasconcelos Andreanne Gomes, Silva de Carvalho Amandda Évelin, Slompo Robson Camilotti, Sá Bruno Silva, Gonçalves Maria Júlia Lima, Lima Moura Liz Nayara Ribeiro da Costa, Brito Ana Karolinne da Silva, França José Vinícius de Sousa, Martins Maria do Carmo de Carvalho E, Rizzo Márcia Dos Santos, Soares Susana, Bastos Verónica, Saldanha de Araujo Felipe, Mogharbel Bassam Felipe, Carvalho Katherine Athayde Teixeira de, Oliveira Helena, Plácido Alexandra, Arcanjo Daniel Dias Rufino, Barbosa Eder Alves, Leite José Roberto de Souza de Almeida
Núcleo de Pesquisa em Morfologia e Imunologia Aplicada, NuPMIA, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília 70910-900, Brazil.
Department of Biomedicine, Centro Universitário do Distrito Federal (UDF), Brasília 70390-045, Brazil.
Pharmaceuticals (Basel). 2023 Jun 20;16(6):905. doi: 10.3390/ph16060905.
Lycopene is a carotenoid with potential use in the treatment of chronic illnesses. Here, different formulations of lycopene were studied: lycopene-rich extract from red guava (LEG), purified lycopene from red guava (LPG) and a self-emulsifying drug delivery system loaded with LPG (nanoLPG). The effects of administering orally various doses of LEG to hypercholesterolemic hamsters were evaluated regarding the liver function of the animals. The cytotoxicity of LPG in Vero cells was analyzed by a crystal violet assay and by fluorescence microscopy. In addition, nanoLPG was employed in stability tests. LPG and nanoLPG were tested for their cytotoxic effect on human keratinocytes and antioxidant capacity on cells in an endothelial dysfunction model in an isolated rat aorta. Finally, the effect of different nanoLPG concentrations on the expression of immune-related genes (, α, and -γ) from peripheral blood mononuclear cells (PBMC) using real-time PCR was also analyzed. Results suggest that LEG, despite not being able to improve blood markers indicative of liver function in hypercholesterolemic hamsters, reduced hepatic degenerative changes. Additionally, LPG did not show cytotoxicity in Vero cells. In relation to nanoLPG, the effects produced by heat stress evaluated by Dynamics Light Scattering (DLS) and visually were loss of color, texture change and phase separation after 15 days without interfering with the droplet size, so the formulation proved to be efficient in stabilizing the encapsulated lycopene. Although LPG and nanoLPG showed moderate toxicity to keratinocytes, which may be related to cell lineage characteristics, both revealed potent antioxidant activity. LPG and nanoLPG showed vasoprotective effects in aortic preparations. The gene expression assay indicates that, although no significant differences were observed in the expression of and , the PBMCs treated with nanoLPG showed a reduction in transcriptional levels of and an increased expression of . Thus, the work adds evidence to the safety of the use of lycopene by humans and shows that tested formulations, mainly nanoLPG due to its stability, stand out as promising and biosafe products for the treatment of diseases that have oxidative stress and inflammation in their etiopathology.
番茄红素是一种类胡萝卜素，在慢性疾病治疗中具有潜在应用价值。在此，对番茄红素的不同制剂进行了研究：来自红番石榴的富含番茄红素的提取物（LEG）、来自红番石榴的纯化番茄红素（LPG）以及负载LPG的自乳化药物递送系统（nanoLPG）。评估了给高胆固醇血症仓鼠口服不同剂量LEG对动物肝功能的影响。通过结晶紫测定法和荧光显微镜分析了LPG对Vero细胞的细胞毒性。此外，将nanoLPG用于稳定性测试。测试了LPG和nanoLPG对人角质形成细胞的细胞毒性作用以及在离体大鼠主动脉内皮功能障碍模型中对细胞的抗氧化能力。最后，还使用实时PCR分析了不同浓度的nanoLPG对外周血单核细胞（PBMC）中免疫相关基因（、α、和-γ）表达的影响。结果表明，尽管LEG无法改善高胆固醇血症仓鼠中指示肝功能的血液指标，但可减少肝脏退行性变化。此外，LPG在Vero细胞中未显示细胞毒性。关于nanoLPG，通过动态光散射（DLS）评估并直观观察到，热应激在15天后产生的影响包括颜色丧失、质地变化和相分离，但不影响液滴大小，因此该制剂被证明在稳定包封的番茄红素方面是有效的。尽管LPG和nanoLPG对角质形成细胞显示出中度毒性，这可能与细胞谱系特征有关，但两者均显示出强大的抗氧化活性。LPG和nanoLPG在主动脉制剂中显示出血管保护作用。基因表达分析表明，尽管在和的表达中未观察到显著差异，但用nanoLPG处理的PBMC显示转录水平降低，而的表达增加。因此，这项工作为人类使用番茄红素的安全性增加了证据，并表明所测试的制剂，主要是nanoLPG因其稳定性，作为治疗在病因学上具有氧化应激和炎症的疾病的有前景且生物安全的产品脱颖而出。
