Zhou Nan, Zheng Deyuan, You Qiao, Chen Taige, Jiang Jiaxuan, Shen Wenhao, Zhang Di, Liu Junpeng, Chen Deyan, Hu Kai
Department of Ophthalmology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China.
State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing 210093, China.
Pharmaceuticals (Basel). 2023 Sep 1;16(9):1240. doi: 10.3390/ph16091240.
Herpes simplex keratitis (HSK) is a blinding eye disease that is initiated by the herpes simplex virus type 1 (HSV-1). Resistance to acyclovir (ACV) and the side effects of corticosteroid drugs have become concerning issues, so it is crucial to develop new antivirals for treating HSK. In this study, we report that biochanin A (BCA), a naturally occurring flavonoid compound, provides multifaceted protective effects with anti-viral, anti-inflammatory, anti-oxidative stress and anti-apoptotic activities to alleviate HSK. The results show that BCA significantly inhibited HSV-1 replication in vitro and further proved that BCA principally influenced the early stage of virus infection. We reveal that BCA downregulated the expression of pro-inflammatory factors triggered by HSV-1, including TNF-α, RANTES, IL-1β and IL-6. Furthermore, BCA treatment alleviated oxidative stress and apoptotic arising from HSV-1 infection. Lastly, we induced HSK in male C57BL/6 mice and treated them with either BCA or phosphate buffer solution (PBS) eye drops. We observed the ocular surface lesions; determined the virus load in the tear fluid, corneas as well as trigeminal ganglions (TGs); and detected the levels of inflammation and apoptosis in the corneas simultaneously. These results show that BCA inhibits HSV-1 and alleviates the corneal lesion degree. Our study illustrates that BCA is a promising therapeutic approach for application in treating HSK.
单纯疱疹病毒性角膜炎（HSK）是一种由1型单纯疱疹病毒（HSV-1）引发的致盲性眼病。对阿昔洛韦（ACV）的耐药性以及皮质类固醇药物的副作用已成为令人担忧的问题，因此开发用于治疗HSK的新型抗病毒药物至关重要。在本研究中，我们报告了天然存在的黄酮类化合物大豆苷元（BCA）具有多方面的保护作用，包括抗病毒、抗炎、抗氧化应激和抗凋亡活性，可减轻HSK。结果表明，BCA在体外显著抑制HSV-1复制，并进一步证明BCA主要影响病毒感染的早期阶段。我们发现BCA下调了由HSV-1触发的促炎因子的表达，包括肿瘤坏死因子-α（TNF-α）、调节激活正常T细胞表达和分泌因子（RANTES）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）。此外，BCA处理减轻了HSV-1感染引起的氧化应激和细胞凋亡。最后，我们在雄性C57BL/6小鼠中诱导HSK，并分别用BCA或磷酸盐缓冲溶液（PBS）滴眼液进行处理。我们观察了眼表病变；测定了泪液、角膜以及三叉神经节（TGs）中的病毒载量；并同时检测了角膜中的炎症和凋亡水平。这些结果表明BCA抑制HSV-1并减轻角膜病变程度。我们的研究表明，BCA是一种有前景的用于治疗HSK的治疗方法。
