Browsing by Author "Horng, Jim-Tong"

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    Orally delivered perilla (Perilla frutescens) leaf extract effectively inhibits SARS-CoV-2 infection in a Syrian hamster model
    (Elsevier, 2022-06-15) Chin, Yuan-Fan; Tang, Wen-Fan; Chang, Yu-Hsiu; Chang, Tein-Yao; Lin, Wen-Chin; Lin, Chia-Yi; Yang, Chuen-Mi; Wu, Hsueh-Ling; Liu, Ping-Cheng; Sun, Jun-Ren; Hsu, Shu-Chen; Lee, Chia-Ying; Lu, Hsuan-Ying; Chang, Jia-Yu; Jheng, Jia-Rong; Chen, Cheng Cheung; Kau, Jyh-Hwa; Huang, Chih-Heng; Chiu, Cheng-Hsun; Hung, Yi-Jen; Tsai, Hui-Ping; Horng, Jim-Tong; Medicine, School of Medicine
    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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    Rosmarinic acid interferes with influenza virus A entry and replication by decreasing GSK3β and phosphorylated AKT expression levels
    (Elsevier, 2022) Jheng, Jia-Rong; Hsieh, Chung-Fan; Chang, Yu-Hsiu; Ho, Jin-Yuan; Tang, Wen-Fang; Chen, Zi-Yi; Liu, Chien-Jou; Lin, Ta-Jen; Huang, Li-Yu; Chern, Jyh-Haur; Horng, Jim-Tong; Biochemistry and Molecular Biology, School of Medicine
    Background: The purpose of this study was to examine the in vivo activity of rosmarinic acid (RA) - a phytochemical with antioxidant, anti-inflammatory, and antiviral properties - against influenza virus (IAV). An antibody-based kinase array and different in vitro functional assays were also applied to identify the mechanistic underpinnings by which RA may exert its anti-IAV activity. Methods: We initially examined the potential efficacy of RA using an in vivo mouse model. A time-of-addition assay and an antibody-based kinase array were subsequently applied to investigate mechanism-of-action targets for RA. The hemagglutination inhibition assay, neuraminidase inhibition assay, and cellular entry assay were also performed. Results: RA increased survival and prevented body weight loss in IAV-infected mice. In vitro experiments revealed that RA inhibited different IAV viruses - including oseltamivir-resistant strains. From a mechanistic point of view, RA downregulated the GSK3β and Akt signaling pathways - which are known to facilitate IAV entry and replication into host cells. Conclusions: RA has promising preclinical efficacy against IAV, primarily by interfering with the GSK3β and Akt signaling pathways.