Xu Yang-Ding, Guo Yu-Jie, Mao He-Rong, Xiong Zhi-Xiang, Luo Meng-Yu, Luo Rui-Qi, Lu Shan, Huang Lu, Hong Yi
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.
International Center for TCM Communication Studies, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Chin Med. 2023 Jun 6;18(1):67. doi: 10.1186/s13020-023-00772-2.
Dermatophyte caused by Trichophyton mentagrophytes is a global disease with a growing prevalence that is difficult to cure. Perilla frutescens (L.) Britt. is an edible and medicinal plant. Ancient books of Traditional Chinese Medicine and modern pharmacological studies have shown that it has potential anti-fungi activity. This is the first study to explore the inhibitory effects of compounds from P. frutescens on Trichophyton mentagrophytes and its mechanism of action coupled with the antifungal activity in vitro from network pharmacology, transcriptomics and proteomics.
Five most potential inhibitory compounds against fungi in P. frutescens was screened with network pharmacology. The antifungal activity of the candidates was detected by a broth microdilution method. Through in vitro antifungal assays screening the compound with efficacy, transcriptomics and proteomics were performed to investigate the pharmacological mechanisms of the effective compound against Trichophyton mentagrophytes. Furthermore, the real-time polymerase chain reaction (PCR) was applied to verify the expression of genes.
The top five potential antifungal compounds in P. frutescens screened by network pharmacology are: progesterone, luteolin, apigenin, ursolic acid and rosmarinic acid. In vitro antifungal assays showed that rosmarinic acid had a favorable inhibitory effect on fungi. The transcriptomic findings exhibited that the differentially expressed genes of fungus after rosmarinic acid intervention were mainly enriched in the carbon metabolism pathway, while the proteomic findings suggested that rosmarinic acid could inhibit the average growth of Trichophyton mentagrophytes by interfering with the expression of enolase in the glycolysis pathway. Comparison of real-time PCR and transcriptomics results showed that the trends of gene expression in glycolytic, carbon metabolism and glutathione metabolic pathways were identical. The binding modes and interactions between rosmarinic acid and enolase were preliminary explored by molecular docking analysis.
The key findings of the present study manifested that rosmarinic acid, a medicinal compound extracted from P. frutescens, had pharmacological activity in inhibiting the growth of Trichophyton mentagrophytes by affecting its enolase expression to reduce metabolism. Rosmarinic acid is expected to be an efficacious product for prevention and treatment of dermatophytes.
须癣毛癣菌引起的皮肤癣菌病是一种全球流行且日益普遍、难以治愈的疾病。紫苏是一种可食用和药用的植物。中医古籍和现代药理学研究表明，它具有潜在的抗真菌活性。这是第一项从网络药理学、转录组学和蛋白质组学方面探索紫苏化合物对须癣毛癣菌的抑制作用及其作用机制以及体外抗真菌活性的研究。
用网络药理学筛选出紫苏中对真菌最具潜在抑制作用的五种化合物。通过肉汤微量稀释法检测候选物的抗真菌活性。通过体外抗真菌试验筛选出具有疗效的化合物，进行转录组学和蛋白质组学研究，以探讨有效化合物对须癣毛癣菌的药理机制。此外，应用实时聚合酶链反应（PCR）验证基因表达。
通过网络药理学筛选出紫苏中潜在的前五种抗真菌化合物为：孕酮、木犀草素、芹菜素、熊果酸和迷迭香酸。体外抗真菌试验表明，迷迭香酸对真菌具有良好的抑制作用。转录组学研究结果显示，迷迭香酸干预后真菌的差异表达基因主要富集在碳代谢途径，而蛋白质组学研究结果表明，迷迭香酸可通过干扰糖酵解途径中烯醇化酶的表达来抑制须癣毛癣菌的平均生长。实时PCR与转录组学结果比较表明，糖酵解、碳代谢和谷胱甘肽代谢途径中的基因表达趋势一致。通过分子对接分析初步探索了迷迭香酸与烯醇化酶之间的结合模式和相互作用。
本研究的主要发现表明，从紫苏中提取的药用化合物迷迭香酸具有通过影响须癣毛癣菌烯醇化酶表达以减少代谢来抑制其生长的药理活性。迷迭香酸有望成为预防和治疗皮肤癣菌病的有效产品。
