Abstract Tuberculosis (TB) is a threat to a large population across the globe. Rapanea melanophloeos (L.) Mez, commonly known as the Cape beech, is a plant that is traditionally used in the treatment of tuberculosis and TB-related symptoms. The aim of this study, was to evaluate the pharmacological effects of a leaf ethanolic extract (1:10, w:v) of R. melanophloeos, as well as different polarity partitions, in conjunction with a fluoroquinolone antimycobacterial drug, ciprofloxacin. The bioassays in this study included the antimycobacterial, antibiofilm and synergistic potential against M. smegmatis. Secondly the antiproliferative and hepatoprotective effect on hepatocytes (HepG2), and, lastly, a potential mechanistic investigation on mycothione, glutathione and thioredoxin reductases. The hexane fraction from the ethanolic plant extract showed relatively good antibiofilm activity with a mean IC50 value of 128.25±4.09 μg/mL. The drug-herb interaction activity of the extract was tested against ciprofloxacin, and it was found that the plant extract acted antagonistically towards the standard drug (FIC > 4). Antiproliferative and hepatoprotective tests were conducted on HepG2 hepatocytes to test the effects on cell viability. The plant was not toxic to the cells but showed no significant hepatoprotective activity against drug-induced hepatotoxic injury, in comparison to the positive control silymarin. Furthermore, the plant extract was tested against glutathione, mycothiol and thioredoxin reductase (human and bacterial analogs) for its inhibitory activity. Rapanea melanophloeos showed higher affinity for the glutathione and mycothiol reductase with relatively high inhibitory activity against the enzymes. The findings from this study indicate the potential adverse effects and drug-herb interactions, associated with the use of R. melanophloeos in the treatment of TB. In addition, this study emphasizes the importance of herb indications and drug interactions, and the term “natural” or “herbal” does not coincide with safe.

中文翻译：

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使用 Rapanea melanophloeos (L.) Mez 对抗分枝杆菌的潜在影响

摘要 结核病 (TB) 是对全球大量人口的威胁。Rapanea melanophloeos (L.) Mez，俗称山毛榉，是一种传统上用于治疗结核病和结核病相关症状的植物。本研究的目的是评估 R. melanophloeos 的叶乙醇提取物 (1:10, w:v) 以及不同极性分区与氟喹诺酮类抗分枝杆菌药物环丙沙星的药理作用。本研究中的生物测定包括抗分枝杆菌、抗生物膜和对耻垢分枝杆菌的协同潜力。其次是对肝细胞 (HepG2) 的抗增殖和保肝作用，最后是对真菌硫酮、谷胱甘肽和硫氧还蛋白还原酶的潜在机制研究。乙醇植物提取物中的己烷级分显示出相对良好的抗生物膜活性，平均 IC50 值为 128.25±4.09 μg/mL。针对环丙沙星测试提取物的药物-草药相互作用活性，发现植物提取物对标准药物具有拮抗作用（FIC > 4）。对 HepG2 肝细胞进行抗增殖和保肝试验以测试对细胞活力的影响。与阳性对照水飞蓟素相比，该植物对细胞无毒，但对药物诱导的肝毒性损伤没有显着的保肝活性。此外，还针对谷胱甘肽、霉菌硫醇和硫氧还蛋白还原酶（人和细菌类似物）测试了植物提取物的抑制活性。Rapanea melanophloeos 对谷胱甘肽和霉菌硫醇还原酶显示出更高的亲和力，对这些酶具有相对较高的抑制活性。这项研究的结果表明潜在的不良反应和药物-草药相互作用，与使用 R. melanophloeos 治疗 TB 相关。此外，这项研究强调了草药适应症和药物相互作用的重要性，“天然”或“草药”一词与安全并不相符。