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Yuan-Fan Chin, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Wen-Fan Tang, Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan
Yu-Hsiu Chang, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Tein-Yao Chang, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Wen-Chin Lin, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Chia-Yi Lin, Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan
Chuen-Mi Yang, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Hsueh-Ling Wu, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Ping-Cheng Li, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Jun-Ren Sun, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Shu-Chen Hsu, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Chia-Ying Lee, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Hsuan-Ying Lu, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Jia-Yu Chang, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Jia-Rong Jheng, Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
Cheng Cheung Chen, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Jyh-Hwa Kau, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Chih-Heng Huang, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Cheng-Hsun Chiu, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
Yi-Jen Hung, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Hui-Ping Tsai, Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
Jim-Tong Horng, Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan, TaiwanFollow

Keywords

COVID-19, hamster, herbal medicine, Perilla frutescens, SARS-CoV-2, serum biomarkers

Abstract

On 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.

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Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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