Third Level Research Laboratory of State Administration of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China.
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, PR China.
J Ethnopharmacol. 2023 Jun 12;309:116339. doi: 10.1016/j.jep.2023.116339. Epub 2023 Mar 2.
Dengue virus (DENV) infection is a global public health issue without effective therapeutic interventions. Chinese medicine with heat-clearing and detoxifying properties has been frequently used in the treatment of viral infection. Ampelopsis Radix (AR) is a traditional Chinese medicine for clearing heat and detoxification that has been widely used in the prevention and treatment of infectious diseases. However, no studies on the effects of AR against viral infection have been reported, thus far.
To explore the anti-DENV activities of the fraction (AR-1) obtained from AR both in vitro and in vivo.
The chemical composition of AR-1 was identified by liquid chromatography-tandem MS (LC‒MS/MS). The antiviral activities of AR-1 were studied in baby hamster kidney fibroblast BHK-21 cells, ICR suckling mice and induction of interferon α/β (IFN-α/β) and IFN-γ R (AG129) mice.
Based on LC‒MS/MS analysis, 60 compounds (including flavonoids, phenols, anthraquinones, alkaloids and other types) were tentatively characterized from AR-1. AR-1 inhibited the cytopathic effect, the production of progeny virus and the synthesis of viral RNA and proteins by blocking DENV-2 binding to BHK-21 cells. Moreover, AR-1 significantly attenuated weight loss, decreased clinical scores and prolonged the survival of DENV-infected ICR suckling mice. Critically, the viral load in blood, brain and kidney tissues and the pathological changes in brain were remarkably alleviated after AR-1 treatment. Further study on AG129 mice showed that AR-1 obviously improved the clinical manifestations and survival rate, reduced viremia, attenuated gastric distension and relieved the pathological lesions caused by DENV.
In summary, this is the first report that AR-1 exhibits anti-DENV effects both in vitro and in vivo, which suggests that AR-1 may be developed as a therapeutic candidate against DENV infection.
登革热病毒（DENV）感染是一个全球性的公共卫生问题，目前尚无有效的治疗干预措施。具有清热解毒特性的中药经常用于治疗病毒感染。白蔹（AR）是一种清热解毒的中药，已广泛用于传染病的预防和治疗。然而，迄今为止，尚未有关于 AR 对病毒感染影响的研究报告。
探讨从 AR 中获得的馏分（AR-1）在体外和体内抗 DENV 的活性。
通过液相色谱-串联质谱（LC-MS/MS）鉴定 AR-1 的化学成分。在乳仓鼠肾成纤维细胞 BHK-21 细胞、ICR 乳鼠和诱导干扰素 α/β（IFN-α/β）和 IFN-γ R（AG129）小鼠中研究 AR-1 的抗病毒活性。
基于 LC-MS/MS 分析，从 AR-1 中初步鉴定出 60 种化合物（包括黄酮类、酚类、蒽醌类、生物碱等类型）。AR-1 通过阻断 DENV-2 与 BHK-21 细胞的结合，抑制细胞病变效应、子代病毒的产生以及病毒 RNA 和蛋白质的合成。此外，AR-1 显著减轻 DENV 感染的 ICR 乳鼠的体重减轻、临床评分降低和存活率延长。重要的是，AR-1 治疗后，血液、脑和肾脏组织中的病毒载量以及脑组织的病理变化明显减轻。在 AG129 小鼠上的进一步研究表明，AR-1 明显改善了临床症状和存活率，降低了病毒血症，减轻了胃胀，并缓解了 DENV 引起的病理损伤。
综上所述，这是首次报道 AR-1 具有体外和体内抗 DENV 作用的报告，这表明 AR-1 可能被开发为治疗 DENV 感染的候选药物。
