Abate Selamu Kebamo, Soni Rohit, Jena Prasanjit, Banerjee Arup, Garabadu Debapriya
Department of Pharmacology, School of Health Sciences, Central University of Punjab, Bathinda, 151401, India.
Laboratory of Virology, Regional Centre for Biotechnology (RCB), Faridabad, Haryana, 121001, India.
J Neuroimmune Pharmacol. 2025 Sep 12;20(1):80. doi: 10.1007/s11481-025-10240-3.
Japanese encephalitis virus (JEV), which belongs to the virus family of Flaviviridae, is a threat to more than three billion people globally. There are no antiviral agents against JEV despite the availability of vaccines. This study considered the need for an effective drug against JEV by evaluating the antiviral and neuroprotective potentials of Chicoric Acid (CA) and Rutin in the in vitro and in vivo models of JE. In the in vitro study, CA and Rutin exhibited variable antiviral potency with IC values ranging from 11.03 to 24.04 µM and 16.45 to 26.84 µM in different treatment approaches. These agents demonstrated significant antiviral effects via viricidal activity and inhibiting the virus's entry into the host cells. In addition, treatment of JEV-infected SH-SY5Y cells with these compounds significantly reduced the intracellular viral load, the proportion of apoptotic cells, and the ROS level in a dose-dependent manner. In the in vivo studies, Rutin (50 mg/kg) significantly increased the survival rate and attenuated the encephalitis symptoms in the JEV-infected mice compared to other doses. Rutin (25 and 50 mg/kg) significantly reduced infectious viral particles, viral RNA, and viral NS3 protein expression in the mice's brains. Additionally, Rutin significantly mitigated JEV-induced neuroinflammation by decreasing microglial activation, inflammasome formation, proinflammatory cytokine, and ROS levels. In conclusion, Rutin exhibits non-specific viricidal activity, reduced viral load, and inflammatory cytokines; thus, it could be a potential therapeutic option in managing JE, subject to future investigations.
日本脑炎病毒（JEV）属于黄病毒科病毒家族，对全球超过30亿人构成威胁。尽管有疫苗可用，但目前尚无针对JEV的抗病毒药物。本研究通过评估菊苣酸（CA）和芦丁在日本脑炎的体外和体内模型中的抗病毒和神经保护潜力，探讨了开发有效抗JEV药物的必要性。在体外研究中，CA和芦丁表现出不同的抗病毒效力，在不同治疗方法下，其半数抑制浓度（IC）值范围为11.03至24.04µM和16.45至26.84µM。这些药物通过杀病毒活性和抑制病毒进入宿主细胞表现出显著的抗病毒作用。此外，用这些化合物处理JEV感染的SH-SY5Y细胞可显著降低细胞内病毒载量、凋亡细胞比例和活性氧水平，且呈剂量依赖性。在体内研究中，与其他剂量相比，芦丁（50mg/kg）显著提高了JEV感染小鼠的存活率并减轻了脑炎症状。芦丁（25和50mg/kg）显著降低了小鼠脑中感染性病毒颗粒、病毒RNA和病毒NS3蛋白的表达。此外，芦丁通过减少小胶质细胞活化、炎性小体形成、促炎细胞因子和活性氧水平，显著减轻了JEV诱导的神经炎症。总之，芦丁具有非特异性杀病毒活性，可降低病毒载量和炎性细胞因子水平；因此，在进一步研究的前提下，它可能是治疗日本脑炎的一种潜在选择。
