病毒性出血性敗血症（viral hemorrhagic septicemia，VHS）對韓國的橄欖˙目鯛（Paralichthys olivaceus）水產養殖業造成了可觀的經濟損失。因此，為了控制病毒性出血性敗血症病毒（viral hemorrhagic septicemia virus，VHSV）感染，急需有效的抗病毒劑。本研究利用Box-Behnken設計和細胞病變減少試驗，得出了一種對VHSV具有最大抗病毒活性的五味子（Sanguisorba officinalis L.）根部精華提取物（OE-SOR）。在優化的提取條件下（55%乙醇濃度，在50°C下提取5小時），經過優化提取條件制備的OE-SOR對VHSV具有強效的抗病毒活性，其50%有效濃度為0.21μg/mL，選擇性指數為340。OE-SOR在斑點減少試驗中也表現出直接的殺毒活性。給予橄欖˙目鯛100mg/kg體重/天的OE-SOR以作為預防（40.0%; p < 0.05）或治療（44.4%; p < 0.05）劑量時，相對生存率較未接受OE-SOR治疗的VHSV感染對照組（分別為100%和90%的死亡率）要高。此外，給予橄欖˙目鯛100mg/kg體重/天的OE-SOR在兩週内，相對於對照組，於給予藥物後的一至兩天，顯示出明顯較高的炎症細胞激素表達（核因子κB，白細胞介素-1β和腫瘤壞死因子-α）。此外，與OE-SOR治療4週的橄欖˙目鯛檢測結果顯示，未觀察到任何血液學或組織學變化。液相色譜-四極杆-飛行時間串聯質譜和三重四極杆串聯質譜分析確定了OE-SOR的主要成分和標記化合物（含量為14.5%）為紫芋苷I。本研究證實，OE-SOR是控制橄欖˙目鯛養殖場病毒性出血性敗血症的有效替代品，因其具有有效的體內抗VHSV活性並增強先天免疫反應。 © 2023. 由Elsevier Ltd.出版。

Viral hemorrhagic septicemia causes considerable economic losses for Korea's olive flounder (Paralichthys olivaceus) aquaculture farms; therefore, effective antiviral agents for controlling viral hemorrhagic septicemia virus (VHSV) infection are imperative. The present study implemented a Box-Behnken design and cytopathic reduction assay to derive an optimized extract of Sanguisorba officinalis L. roots (OE-SOR) with maximum antiviral activity against VHSV. OE-SOR prepared under optimized extraction conditions (55% ethanol concentration at 50 °C for five hours) exhibited potent antiviral activity against VHSV, with a 50% effective 0.21 μg/mL concentration and a 340 selective index. OE-SOR also showed direct virucidal activity in the plaque reduction assay. Administering OE-SOR to olive flounder exhibited substantial efficacies against VHSV infection. Fish receiving 100 mg/kg body weight/day of OE-SOR as a preventive (40.0%; p < 0.05) or therapeutic (44.4%; p < 0.05) exhibited a higher relative survival than the untreated VHSV-infected control group (mortalities of 100% and 90%, respectively). In addition, fish fed with OE-SOR (100 mg/kg body weight/day) for two weeks conveyed a significantly higher inflammatory cytokine expression (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB], interleukin-1 beta [IL-1β], and tumor necrosis factor-alpha [TNF-α]) than the control group one to two days post-administration. Moreover, no hematological or histological changes were observed in olive flounder treated with OE-SOR over four weeks. Liquid chromatography-quadrupole-time of flight tandem mass spectrometry and -triple quadrupole tandem mass spectrometry analyses identified ziyuglycoside I as a prominent OE-SOR constituent and marker compound (content: 14.5%). This study verifies that OE-SOR is an effective alternative for controlling viral hemorrhagic septicemia in olive flounder farms as it exhibits efficient in vivo anti-VHSV activity and increases innate immune responses.Copyright © 2023. Published by Elsevier Ltd.