Journal of Food and Drug Analysis (JFDA)
【Update Date:2022-06-20】unit:
Orally delivered perilla (Perilla frutescens) leaf extract effectively inhibits SARS-CoV-2 infection in a syrian hamster model
Yuan-Fan Chin a,1, Wen-Fan Tang b,1, Yu-Hsiu Chang a,1, Tein-Yao Chang a,c,1, Wen-Chin Lin a,c,1, Chia-Yi Lin b, Chuen-Mi Yang a, Hsueh-Ling Wu a, Ping-Cheng Liu a,Jun-Ren Sun a,c,j, Shu-Chen Hsu a, Chia-Ying Lee a, Hsuan-Ying Lu a, Jia-Yu Chang a,Jia-Rong Jheng f, Cheng Cheung Chen a,d, Jyh-Hwa Kau a,d,j, Chih-Heng Huang a,d,e,Cheng-Hsun Chiu g, Yi-Jen Hung a, Hui-Ping Tsai a,*,2, Jim-Tong Horng b,g,h,i,**,3
a Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan
b Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan
c Department of Pathology and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense
Medical Center, Taipei 114, Taiwan
d Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan
e Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
f Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
g Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
h Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan
i Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan
j Division of Infectious Disease and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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 virusinduced 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 (3e4 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.
Keywords: COVID-19, Hamster, Herbal medicine, Perilla frutescens, SARS-CoV-2, Serum biomarkers
https://doi.org/10.38212/2224-6614.3412
(https://www.jfda-online.com/journal/vol30/iss2/6/)