In vivo and in silico toxicity profiling of aerial part of Andrographis paniculata revealed potential to precipitate organs toxicity

A. Agbaje, M. O. Daniyan, I. Olawuni
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Abstract

The many medicinal properties of Andrographis paniculata have made it an important resource in drug discovery. The commonly used powdered aerial part of A. paniculata is however a subject of abuse occasioned by indiscriminate use, raising safety concerns. In this study, we evaluated the safety profile of the suspension of the powdered aerial part of A. paniculata in male and female rats using single and repeated dose toxicity profiling, and the in silico toxicity profiling of its known phytochemicals, with a view to establishing organs safety. Our results showed significant sex dependent alterations in key haematological and biochemical indices. Significant alteration in liver and kidney histo-architectures were consistent with the observed significant increase in AST/ALT ratio and with the in silico toxicity screening of A. paniculata phytochemicals, including andrographolide, which showed potential for hepatotoxicity, binding of proteins and DNA, and inhibition of hERG II. We conclude that, while taking advantage of the many medicinal benefits of this plant, the unguarded and indiscriminate uses may precipitate organ toxicity, induce cellular alteration and potentiate possible cardiovascular risk.
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对穿心莲地上部的体内和硅毒性分析显示穿心莲有器官沉淀毒性的潜力
穿心莲的多种药用特性使其成为新药开发的重要资源。然而,由于滥用,经常使用的金针叶的粉末状部分是滥用的对象,引起了安全问题。本研究通过单次和重复给药毒性分析,以及已知植物化学物质的硅毒性分析,评价了金针叶地上部分粉末悬浮液在雄性和雌性大鼠体内的安全性,以期建立器官安全性。我们的研究结果显示,关键的血液学和生化指标存在显著的性别依赖性变化。肝脏和肾脏组织结构的显著改变与观察到的AST/ALT比值的显著升高以及穿心莲内酯等植物化学物质的硅毒性筛选一致,穿心莲内酯显示出潜在的肝毒性、蛋白质和DNA的结合以及对hERG II的抑制。我们的结论是,在利用这种植物的许多药用价值的同时,不加保护和不加选择地使用可能会导致器官毒性,诱导细胞改变并可能增加心血管风险。
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