Department of Microbiology, Stellenbosch University, Private Bag X1, Stellenbosch 7602, South Africa.
Department of Microbiology, Stellenbosch University, Private Bag X1, Stellenbosch 7602, South Africa; Central Analytical Facility, Stellenbosch University, Private Bag X1, Stellenbosch 7602, South Africa.
J Ethnopharmacol. 2019 May 10;235:122-132. doi: 10.1016/j.jep.2019.02.008. Epub 2019 Feb 6.
Limitations of clinical antifungal treatments and drug-resistance are drivers of the search for novel antifungal strategies. Extracts prepared from the tubers of the medicinal plant, Pelargonium sidoides, are known for their antiviral and antibacterial activities and are used in ethnomedicine for the treatment of acute respiratory infections. Their impact on fungi has not been well characterised. Here, we provide a first report on the antifungal activity of a P. sidoides aerial tissue extract against Cryptococcus neoformans as well as the effects of both tuber and aerial tissue extracts on selected virulence factors.
Novel antimicrobial strategies that target multiple cellular pathways or make use of anti-pathogenic compounds that inhibit virulence factors have been proposed. This work aimed to evaluate P. sidoides plant parts for their anticryptococcal activity and antipathogenic properties on selected virulence factors.
The antifungal activity of crude P. sidoides tuber and aerial tissue extracts (15% m/m ethanol) were compared using a modified colourimetric antifungal susceptibility test. Fungicidal activity of the extracts was confirmed by plate counts. To test yeast resistance to the extracts, it was conditioned by multiple passages in sub-lethal doses followed by antifungal susceptibility testing. Cytotoxicity of the extracts was tested with a blood agar haemolysis assay. Extracts were evaluated for the presence of multiple bioactive compounds by solid-phase fractionation and visualisation by thin-layer chromatography in combination with bioassays. The influence of extracts on the production of the polysaccharide capsule, ergosterol content as well as laccase and urease activities were also evaluated. Cell surface variations after extract exposure were visualised by scanning electron microscopy (SEM).
Both tuber and aerial tissue extracts were fungicidal and contained multiple bioactive compounds which constrained the development of antifungal resistance. No haemolytic activity was observed, and the extracts did not appear to target ergosterol biosynthesis. However, the extracts displayed anti-pathogenic potential by significantly inhibiting laccase and urease activity while also significantly reducing capsule size. SEM revealed notable cell surface variations and provided support for the observed reduction in capsule size.
Our results provide support to the exploration of medicinal plants as sources of alternative antifungal therapies and the potential use of multicomponent inhibition and or virulence attenuation for next-generation treatment strategies. Our data also provide relevant information that may support the further use of P. sidoides in traditional medicines as well as in commercialised phytopharmaceuticals.
临床抗真菌治疗的局限性和耐药性是寻找新型抗真菌策略的驱动因素。药用植物天竺葵的根茎提取物以其抗病毒和抗菌活性而闻名，在民族医学中用于治疗急性呼吸道感染。然而，其对真菌的影响尚未得到很好的描述。在这里，我们首次报道了天竺葵地上组织提取物对新生隐球菌的抗真菌活性，以及根茎和地上组织提取物对选定毒力因子的影响。
已经提出了针对多种细胞途径的新型抗菌策略，或者利用抑制毒力因子的抗病原体化合物。本研究旨在评估天竺葵植物部分的抗隐球菌活性和对选定毒力因子的抗病原体特性。
使用改良的比色抗真菌药敏试验比较了天竺葵根茎和地上组织粗提取物（15% m/m 乙醇）的抗真菌活性。通过平板计数确认提取物的杀菌活性。为了测试酵母对提取物的耐药性，将其在亚致死剂量下多次传代，然后进行抗真菌药敏试验。用血琼脂溶血试验测试提取物的细胞毒性。通过固相分馏和薄层层析结合生物测定来评估提取物中多种生物活性化合物的存在。还评估了提取物对多糖荚膜产生、麦角固醇含量以及漆酶和脲酶活性的影响。扫描电子显微镜（SEM）观察提取物暴露后细胞表面的变化。
根茎和地上组织提取物均具有杀菌作用，并含有多种可限制抗真菌耐药性发展的生物活性化合物。未观察到溶血活性，并且提取物似乎不针对麦角固醇生物合成。然而，提取物通过显著抑制漆酶和脲酶活性，同时显著减小荚膜大小，显示出抗病原体的潜力。SEM 显示出明显的细胞表面变化，并为观察到的荚膜大小减小提供了支持。
我们的研究结果为探索药用植物作为替代抗真菌疗法的来源提供了支持，也为下一代治疗策略中的多成分抑制和/或毒力衰减提供了潜力。我们的数据还提供了相关信息，可能支持进一步将天竺葵用于传统医学以及商业化的植物药中。
