Chin, Yuan-FanTang, Wen-FanChang, Yu-HsiuChang, Tein-YaoLin, Wen-ChinLin, Chia-YiYang, Chuen-MiWu, Hsueh-LingLiu, Ping-ChengSun, Jun-RenHsu, Shu-ChenLee, Chia-YingLu, Hsuan-YingChang, Jia-YuJheng, Jia-RongChen, Cheng CheungKau, Jyh-HwaHuang, Chih-HengChiu, Cheng-HsunHung, Yi-JenTsai, Hui-PingHorng, Jim-Tong2023-10-092023-10-092022-06-15Chin YF, Tang WF, Chang YH, et al. Orally delivered perilla (Perilla frutescens) leaf extract effectively inhibits SARS-CoV-2 infection in a Syrian hamster model. J Food Drug Anal. 2022;30(2):252-270. Published 2022 Jun 15. doi:10.38212/2224-6614.3412https://hdl.handle.net/1805/36219On analyzing the results of cell-based assays, we have previously shown that perilla (Perilla frutescens) leaf extract (PLE), a food supplement and orally deliverable traditional Chinese medicine approved by the Taiwan Food and Drug Administration, effectively inhibits SARS-CoV-2 by directly targeting virions. PLE was also found to modulate virus-induced cytokine expression levels. In this study, we explored the anti-SARS-CoV-2 activity of PLE in a hamster model by examining viral loads and virus-induced immunopathology in lung tissues. Experimental animals were intranasally challenged with different SARS-CoV-2 doses. Jugular blood samples and lung tissue specimens were obtained in the acute disease stage (3–4 post-infection days). As expected, SARS-CoV-2 induced lung inflammation and hemorrhagic effusions in the alveoli and perivascular areas; additionally, it increased the expression of several immune markers of lung injury – including lung Ki67-positive cells, Iba-1-positive macrophages, and myeloperoxidase-positive neutrophils. Virus-induced lung alterations were significantly attenuated by orally administered PLE. In addition, pretreatment of hamsters with PLE significantly reduced viral loads and immune marker expression. A purified active fraction of PLE was found to confer higher antiviral protection. Notably, PLE prevented SARS-CoV-2-induced increase in serum markers of liver and kidney function as well as the decrease in serum high-density lipoprotein and total cholesterol levels in a dose-dependent fashion. Differently from lung pathology, monitoring of serum biomarkers in Syrian hamsters may allow a more humane assessment of the novel drugs with potential anti-SARS-CoV-2 activity. Our results expand prior research by confirming that PLE may exert an in vivo therapeutic activity against SARS-CoV-2 by attenuating viral loads and lung tissue inflammation, which may pave the way for future clinical applications.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalCOVID-19HamsterHerbal medicinePerilla frutescensSARS-CoV-2Serum biomarkersArticle