Tarasuk Mayuri, Songprakhon Pucharee, Muhamad Phunuch, Panya Aussara, Sattayawat Pachara, Yenchitsomanus Pa-Thai
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand.
Division of Molecular Medicine, Research Department, and Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Sci Rep. 2024 Apr 23;14(1):9322. doi: 10.1038/s41598-024-60070-1.
Dengue virus (DENV) infection can lead to severe outcomes through a virus-induced cytokine storm, resulting in vascular leakage and inflammation. An effective treatment strategy should target both virus replication and cytokine storm. This study identified Kaempferia galanga L. (KG) extract as exhibiting anti-DENV activity. The major bioactive compound, ethyl-p-methoxycinnamate (EPMC), significantly reduced DENV-2 infection, virion production, and viral protein synthesis in HepG2 and A549 cells, with half-maximal effective concentration (EC) values of 22.58 µM and 6.17 µM, and impressive selectivity indexes (SIs) of 32.40 and 173.44, respectively. EPMC demonstrated efficacy against all four DENV serotypes, targeting the replication phase of the virus life cycle. Importantly, EPMC reduced DENV-2-induced cytokines (IL-6 and TNF-α) and chemokines (RANTES and IP-10), as confirmed by immunofluorescence and immunoblot analyses, indicating inhibition of NF-κB activation. EPMC's role in preventing excessive inflammatory responses suggests it as a potential candidate for dengue treatment. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness for EPMC were predicted using SwissADME and ProTox II servers, showing good drug-like properties without toxicity. These findings highlight KG extract and EPMC as promising candidates for future anti-dengue therapeutics, offering a dual-action approach by inhibiting virus replication and mitigating inflammatory reactions.
登革病毒（DENV）感染可通过病毒诱导的细胞因子风暴导致严重后果，引发血管渗漏和炎症。有效的治疗策略应同时针对病毒复制和细胞因子风暴。本研究确定高良姜（KG）提取物具有抗登革病毒活性。主要生物活性化合物对甲氧基肉桂酸乙酯（EPMC）在HepG2和A549细胞中显著降低了DENV-2感染、病毒粒子产生和病毒蛋白合成，半数有效浓度（EC）值分别为22.58 μM和6.17 μM，选择性指数（SIs）分别高达32.40和173.44。EPMC对所有四种登革病毒血清型均有疗效，作用于病毒生命周期的复制阶段。重要的是，免疫荧光和免疫印迹分析证实，EPMC降低了DENV-2诱导的细胞因子（IL-6和TNF-α）和趋化因子（RANTES和IP-10），表明其抑制了NF-κB激活。EPMC在预防过度炎症反应中的作用表明它是登革热治疗的潜在候选药物。使用SwissADME和ProTox II服务器预测了EPMC的吸收、分布、代谢、排泄及毒性（ADMET）和类药性，结果显示其具有良好的类药性质且无毒性。这些发现突出了KG提取物和EPMC作为未来抗登革热治疗药物的潜力候选物，通过抑制病毒复制和减轻炎症反应提供了一种双重作用方法。
