Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis. (October 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Pharmacological research. Volume 184(2022)
• Publication Date: 2022-10
• Subjects: 5-caffeoylquinic acid (PubChem CID: 5280633) -- 3-caffeoylquinic acid (PubChem CID: 1794427) -- 4-caffeoylquinic acid (PubChem CID: 9798666) -- Quercetin 3-galactoside (PubChem CID: 5281643) -- Quercetin 3-glucoside (PubChem CID: 5280804) -- Quercetin 3-rhamnoside (PubChem CID: 5280459) -- Baicalin (PubChem CID: 64982) -- Norwogonin 7-glucuronide (PubChem CID: 44258552) -- Oroxyloside (PubChem CID: 14655552) -- Glycyrrhizic acid (PubChem CID: 14982); COVID-19 -- NRICM102 -- Pulmonary embolism -- Pulmonary fibrosis -- Traditional Chinese medicine; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2022.106424
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: 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-1β, 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. Graphical Abstract: ga1 Highlights: Effective intervention is urgently needed for severe COVID-19 patients at higher risks of fatal pulmonary complications. NRICM102 significantly ameliorates severe COVID-19-related embolic and fibrotic pulmonary injury in vitro and in vivo. NRICM102 exhibits its therapeutic properties via regulation of TLR/NET axis signaling pathways.