Reis Sonia Regina I N, Valente Ligia M M, Sampaio André L, Siani Antonio C, Gandini Mariana, Azeredo Elzinandes L, D'Avila Luiz A, Mazzei José L, Henriques Maria das Graças M, Kubelka Claire F
Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil.
Int Immunopharmacol. 2008 Mar;8(3):468-76. doi: 10.1016/j.intimp.2007.11.010. Epub 2007 Dec 26.
Uncaria tomentosa (Willd.) DC., a large woody vine native to the Amazon and Central American rainforests has been used medicinally by indigenous peoples since ancient times and has scientifically proven immunomodulating, anti-inflammatory, cytotoxic and antioxidant activities. Several inflammatory mediators that are implicated in vascular permeability and shock are produced after Dengue Virus (DENV) infection by monocytes, the primary targets for virus replication. Here we assessed the immunoregulatory and antiviral activities from U. tomentosa-derived samples, which were tested in an in vitro DENV infection model. DENV-2 infected human monocytes were incubated with U. tomentosa hydro-alcoholic extract or either its pentacyclic oxindole alkaloid-enriched or non-alkaloid fractions. The antiviral activity was determined by viral antigen (DENV-Ag) detection in monocytes by flow cytometry. Our results demonstrated an in vitro inhibitory activity by both extract and alkaloidal fraction, reducing DENV-Ag+ cell rates in treated monocytes. A multiple microbead immunoassay was applied for cytokine determination (TNF-alpha, IFN-alpha, IL-6 and IL-10) in infected monocyte culture supernatants. The alkaloidal fraction induced a strong immunomodulation: TNF-alpha and IFN-alpha levels were significantly decreased and there was a tendency towards IL-10 modulation. We conclude that the alkaloidal fraction was the most effective in reducing monocyte infection rates and cytokine levels. The antiviral and immunomodulating in vitro effects from U. tomentosa pentacyclic oxindole alkaloids displayed novel properties regarding therapeutic procedures in Dengue Fever and might be further investigated as a promising candidate for clinical application.
猫爪草（Uncaria tomentosa (Willd.) DC.）是一种原产于亚马逊和中美洲雨林的大型木质藤本植物，自古以来就被当地居民用于医学，并且具有经科学验证的免疫调节、抗炎、细胞毒性和抗氧化活性。登革病毒（DENV）感染后，作为病毒复制主要靶点的单核细胞会产生几种与血管通透性和休克有关的炎症介质。在此，我们评估了猫爪草衍生样品的免疫调节和抗病毒活性，并在体外DENV感染模型中对其进行了测试。将DENV-2感染的人类单核细胞与猫爪草水醇提取物或其富含五环氧化吲哚生物碱的部分或非生物碱部分一起孵育。通过流式细胞术检测单核细胞中的病毒抗原（DENV-Ag）来确定抗病毒活性。我们的结果表明，提取物和生物碱部分均具有体外抑制活性，可降低处理后单核细胞中DENV-Ag+细胞的比例。应用多重微珠免疫测定法测定感染单核细胞培养上清液中的细胞因子（TNF-α、IFN-α、IL-6和IL-10）。生物碱部分诱导了强烈的免疫调节：TNF-α和IFN-α水平显著降低，并且存在IL-10调节的趋势。我们得出结论，生物碱部分在降低单核细胞感染率和细胞因子水平方面最为有效。猫爪草五环氧化吲哚生物碱的体外抗病毒和免疫调节作用在登革热治疗程序方面显示出新颖的特性，可能作为一种有前途的临床应用候选物进行进一步研究。
