Drug Design, Development and Therapy (Dec 2022)
Antiviral Activity of Oridonin Against Herpes Simplex Virus Type 1
Abstract
Kai Jiang,1,2 Jing Feng,2 Xia Qi,2 Lili Ran,2 Lixin Xie2 1Department of Ophthalmology, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, People’s Republic of China; 2Eye Institute of Shandong First Medical University, Eye Hospital of Shandong First Medical University, Qingdao, People’s Republic of ChinaCorrespondence: Lixin Xie, Shandong Eye Institute, 5 Yan’erdao Road, Qingdao, 266071, Tel +8613335026472, Email [email protected]: In search of new potent treatment of herpes simplex keratitis (HSK), inhibitory effect of oridonin (Ori) on herpes simplex virus type 1 (HSV-1) was validated by experiments.Methods: For evaluating inhibitory effect of oridonin on herpes simplex virus type 1, a series of in-vivo and in-vitro studies were carried out. Mouse HSV-1 infection model was used in the in-vivo experiments. Experimental mice were classified in five different groups: Mock (mock-infected), HSV-1+ DMSO, HSV-1+ Ori, HSV-1+ ACV, combined Ori and ACV+HSV-1. Corneas of Mock, HSV-1+ DMSO, HSV-1+ Ori group were sent for mRNA-sequencing after 3 days post infection (dpi). The expression of virus and host-related genes was evaluated by quantitative real-time polymerase chain reaction (qPCR). Vero cells HSV-1 infection models were used in the in-vitro experiments.Results: The application of ACV, Oridonin alone or a combination of both could alleviate HSV-1 severity and inhibit HSV-1 virus replication in C57BL/6 mice models. qPCR showed that compared with mock group, the expression of interleukin-6 (il-6), interleukin-1α (il-1α), and Tumor-necrosis factor-alpha (tnf-α) was up-regulated in DMSO+HSV-1 group and suppressed in other three group. Moreover, the expression of nod-like receptor protein (nlrp3), caspase 1 and interleukin-1β (il-1β) were depressed in the oridonin-treated group. Oridonin significantly inhibits HSV-1 replication, HSV-1 related gene expression, and the production of progeny HSV-1 viruses in vitro. Besides, oridonin affect the replication phase but not HSV-1 entry or penetration and cannot inactivate HSV-1.Conclusion: Oridonin alleviates herpes simplex keratitis infection in mouse, which may be attributed to inhibition of the NLRP3-inflammasome-IL-1β pathway. Our study illustrates that Oridonin has potential promise for application in treating HSK and other diseases caused by HSV-1 infection.Keywords: oridonin, HSV-1, herpes simplex keratitis, herb, nlrp3, inflammasome
