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Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis.
Wei, Wen-Chi; Liaw, Chia-Ching; Tsai, Keng-Chang; Chiou, Chun-Tang; Tseng, Yu-Hwei; Chiou, Wen-Fei; Lin, Yu-Chi; Tsai, Chia-I; Lin, Chen-Shien; Lin, Chen-Sung; Liou, Kuo-Tong; Yu, I-Shing; Shen, Yuh-Chiang; Su, Yi-Chang.
Afiliación
  • Wei WC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan.
  • Liaw CC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600355, Taiwan.
  • Tsai KC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan; Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, Taiwan.
  • Chiou CT; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan.
  • Tseng YH; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan.
  • Chiou WF; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan.
  • Lin YC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan.
  • Tsai CI; Department of Traditional Chinese Medicine, Taichung Veterans General Hospital, Taichung 407204, Taiwan.
  • Lin CS; Department of Chinese Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 424033, Taiwan.
  • Lin CS; Division of Thoracic Surgery, Department of Surgery, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 424033, Taiwan.
  • Liou KT; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan.
  • Yu IS; Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei 100233, Taiwan.
  • Shen YC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan. Electronic address: yuhcs@nricm.edu.tw.
  • Su YC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112026, Taiwan. Electronic address: sychang@nricm.edu.tw.
Pharmacol Res ; 184: 106424, 2022 10.
Article en En | MEDLINE | ID: mdl-36064077
The global COVID-19 pandemic remains a critical public health threat, as existing vaccines and drugs appear insufficient to halt the rapid transmission. During an outbreak from May to August 2021 in Taiwan, patients with severe COVID-19 were administered NRICM102, which was a traditional Chinese medicine (TCM) formula developed based on its predecessor NRICM101 approved for treating mild cases. This study aimed to explore the mechanism of NRICM102 in ameliorating severe COVID-19-related embolic and fibrotic pulmonary injury. NRICM102 was found to disrupt spike protein/ACE2 interaction, 3CL protease activity, reduce activation of neutrophils, monocytes and expression of cytokines (TNF-α, IL-1ß, IL-6, IL-8), chemokines (MCP-1, MIP-1, RANTES) and proinflammatory receptor (TLR4). NRICM102 also inhibited the spread of virus and progression to embolic and fibrotic pulmonary injury through reducing prothrombotic (vWF, PAI-1, NET) and fibrotic (c-Kit, SCF) factors, and reducing alveolar type I (AT1) and type II (AT2) cell apoptosis. NRICM102 may exhibit its protective capability via regulation of TLRs, JAK/STAT, PI3K/AKT, and NET signaling pathways. The study demonstrates the ability of NRICM102 to ameliorate severe COVID-19-related embolic and fibrotic pulmonary injury in vitro and in vivo and elucidates the underlying mechanisms.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Embolia Pulmonar / Lesión Pulmonar / Tratamiento Farmacológico de COVID-19 Límite: Humans Idioma: En Revista: Pharmacol Res Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Embolia Pulmonar / Lesión Pulmonar / Tratamiento Farmacológico de COVID-19 Límite: Humans Idioma: En Revista: Pharmacol Res Asunto de la revista: FARMACOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Países Bajos