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从一般毒理学到 DNA 断裂:Plinia cauliflora(Mart.)Kausel 的安全性评估。

From general toxicology to DNA disruption: A safety assessment of Plinia cauliflora (Mart.) Kausel.

机构信息

Laboratory of Electrophysiology and Cardiovascular Pharmacology - LEFaC, Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil.

Laboratory of Preclinical Research of Natural Products, Paranaense University, Umuarama, PR, Brazil.

出版信息

J Ethnopharmacol. 2020 Aug 10;258:112916. doi: 10.1016/j.jep.2020.112916. Epub 2020 Apr 28.

DOI:10.1016/j.jep.2020.112916
PMID:32360045
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Plinia cauliflora (Mart.) Kausel (Myrtaceae) is popularly known as "jaboticaba" or "jaboticaba". The fruit is appreciated for both fresh consumption and the manufacture of jelly, juice, ice cream, fermented beverages, and liqueurs. The more widespread traditional use of the plant involves the treatment of diarrhea, which utilizes all parts of the plant, including the fruit peels.

AIM OF THE STUDY

We sought to elucidate possible risks of the administration of an ethanol-soluble fraction that was obtained from an infusion of P. cauliflora fruit peels (SEIPC). We performed a series of experiments to evaluate possible toxicity, in which we administered SEIPC orally both acutely and repeatedly for 28 days. We also evaluated possible endocrine-disruptive and genotoxic effects in eukaryotic cells. The possible mutagenic activity of SEIPC was evaluated using reverse mutation (Ames) assays.

MATERIALS AND METHODS

SEIPC was produced and chemically characterized by LC-DAD-MS. Acute toxicity and behavioral and physiological alterations were evaluated in the modified Irwin test. Respiratory rate, arterial blood gas, electrocardiography, respiratory rate, heart rate, and blood pressure were evaluated, and hematological, biochemical, and histopathological analyses were performed after 28 days of oral treatment. The comet assay, mammalian erythrocyte micronucleus test, uterotrophic test, Hershberger bioassay, and AMES test were performed using appropriate protocols.

RESULTS

From SEIPC, ellagic acid and derivatives, flavonols and anthocyanidins, as well as citric acid and gallic acid, were annotated by LC-DAD-MS. We did not observed any significant toxic effects after acute or prolonged SEIPC treatment. No endocrine-disruptive or mutagenic effects were observed.

CONCLUSIONS

The present study found that SEIPC did not cause any significant alterations of various corporeal systems, including cardiac electrical activity, body temperature, respiratory rate, and arterial pressure. No alterations of biochemical, hematological, or blood gas parameters were observed. SEIPC did not cause any perturbations of the endocrine system or mutagenic, cytotoxic, or genotoxic effects. These findings substantiate the safe clinical use of P. cauliflora.

摘要

民族药理学相关性

Plinia cauliflora (Mart.) Kausel(桃金娘科)俗称“嘉宝果”或“嘉宝果”。其果实不仅可鲜食,还可用于制作果冻、果汁、冰淇淋、发酵饮料和利口酒。该植物更为广泛的传统用途是治疗腹泻,其使用了植物的所有部分,包括果皮。

研究目的

我们试图阐明从 Plinia cauliflora 果皮的浸提物中获得的乙醇可溶部分(SEIPC)给药的可能风险。我们进行了一系列实验来评估可能的毒性,包括急性和重复口服给予 SEIPC 长达 28 天。我们还评估了真核细胞中可能的内分泌干扰和遗传毒性作用。使用回复突变(Ames)试验评估 SEIPC 的可能诱变活性。

材料和方法

通过 LC-DAD-MS 生产和化学表征 SEIPC。在改良的 Irwin 试验中评估急性毒性和行为及生理变化。在口服治疗 28 天后评估呼吸频率、动脉血气、心电图、呼吸频率、心率和血压,并进行血液学、生物化学和组织病理学分析。使用适当的方案进行彗星试验、哺乳动物红细胞微核试验、子宫增重试验、Hershberger 生物测定和 Ames 试验。

结果

通过 LC-DAD-MS 注释了 SEIPC 中的鞣花酸及其衍生物、类黄酮和花色苷以及柠檬酸和没食子酸。在急性或长期 SEIPC 治疗后,未观察到任何显著的毒性作用。未观察到内分泌干扰或致突变作用。

结论

本研究发现 SEIPC 不会引起包括心脏电活动、体温、呼吸频率和动脉压在内的各种身体系统的任何显著改变。未观察到生化、血液学或血气参数的改变。SEIPC 不会引起内分泌系统的任何紊乱或致突变、细胞毒性或遗传毒性作用。这些发现证实了 Plinia cauliflora 的安全临床应用。

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