Gómez-Calderón Cecilia, Mesa-Castro Carol, Robledo Sara, Gómez Sergio, Bolivar-Avila Santiago, Diaz-Castillo Fredyc, Martínez-Gutierrez Marlen
Grupo de Investigación en Ciencias Animales-GRICA, Universidad Cooperativa de Colombia, Calle 30A # 33-51, Bucaramanga, Colombia.
Facultad de Ciencias de la Salud, Programa de Bacteriología y Laboratorio Clínico, Grupo de investigación en manejo clínico - CLINIUDES, Universidad de Santander UDES, Bucaramanga, Colombia.
BMC Complement Altern Med. 2017 Jan 18;17(1):57. doi: 10.1186/s12906-017-1562-1.
The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. For this reason, the search for compounds with antiviral potential, either as licensed drugs or in natural products, is a research priority. The objective of this study was to identify some of the compounds that are present in Mammea americana (M. americana) and Tabernaemontana cymosa (T. cymosa) plants and, subsequently, to evaluate their cytotoxicity in VERO cells and their potential antiviral effects on DENV and CHIKV infections in those same cells.
Dry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa.. The cytotoxicity of each compound was subsequently assessed by the MTT method (at concentrations from 400 to 6.25 μg/mL). Pre- and post-treatment antiviral assays were performed at non-toxic concentrations; the resulting DENV inhibition was evaluated by Real-Time PCR, and the CHIKV inhibition was tested by the plating method. The results were analyzed by means of statistical analysis.
The compounds showed low toxicity at concentrations ≤ 200 μg/mL. The compounds coumarin A and coumarin B, which are derived from the M. americana plant, significantly inhibited infection with both viruses during the implementation of the two experimental strategies employed here (post-treatment with inhibition percentages greater than 50%, p < 0.01; and pre-treatment with percentages of inhibition greater than 40%, p < 0.01). However, the lupeol acetate and voacangine compounds, which were derived from the T. cymosa plant, only significantly inhibited the DENV infection during the post-treatment strategy (at inhibition percentages greater than 70%, p < 0.01).
In vitro, the coumarins are capable of inhibiting infection by DENV and CHIKV (with inhibition percentages above 50% in different experimental strategies), which could indicate that these two compounds are potential antivirals for treating Dengue and Chikungunya fever. Additionally, lupeol acetate and voacangine efficiently inhibit infection with DENV, also turning them into promising antivirals for Dengue fever.
登革热病毒（DENV）和基孔肯雅病毒（CHIKV）的传播在全球范围内有所增加，部分原因是缺乏特异性抗病毒治疗。因此，寻找具有抗病毒潜力的化合物，无论是作为已获许可的药物还是天然产物中的成分，都是研究的重点。本研究的目的是鉴定美洲山竹子（Mammea americana，M. americana）和聚花萝芙木（Tabernaemontana cymosa，T. cymosa）植物中存在的一些化合物，随后评估它们对VERO细胞的细胞毒性以及对这些细胞中DENV和CHIKV感染的潜在抗病毒作用。
对美洲山竹子和聚花萝芙木种子的干燥乙醇提取物进行开放柱色谱分离，鉴定出四种化合物：两种香豆素，源自美洲山竹子；以及源自聚花萝芙木的乙酸羽扇豆醇酯和沃坎京。随后通过MTT法（浓度为400至6.25μg/mL）评估每种化合物的细胞毒性。在无毒浓度下进行预处理和后处理抗病毒试验；通过实时荧光定量PCR评估由此产生的DENV抑制作用，并通过平板法测试CHIKV抑制作用。通过统计分析对结果进行分析。
这些化合物在浓度≤ 200μg/mL时显示出低毒性。源自美洲山竹子植物的香豆素A和香豆素B化合物，在采用的两种实验策略实施过程中，均显著抑制了两种病毒的感染（后处理时抑制率大于50%，p < 0.01；预处理时抑制率大于40%，p < 0.01）。然而，源自聚花萝芙木植物的乙酸羽扇豆醇酯和沃坎京化合物，仅在采用后处理策略时显著抑制了DENV感染（抑制率大于70%，p < 0.01）。
在体外，香豆素能够抑制DENV和CHIKV的感染（在不同实验策略中抑制率高于50%），这可能表明这两种化合物是治疗登革热和基孔肯雅热的潜在抗病毒药物。此外，乙酸羽扇豆醇酯和沃坎京能有效抑制DENV感染，也使其成为治疗登革热的有前景的抗病毒药物。
