NRICM101 ameliorates SARS-CoV-2-S1-induced pulmonary injury in K18-hACE2 mice model.

Autor:	Wei WC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Tsai KC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.; Ph.D Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan., Liaw CC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.; Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan., Chiou CT; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Tseng YH; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Liao GY; Institute of Physiology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan., Lin YC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Chiou WF; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Liou KT; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Yu IS; Laboratory Animal Center, National Taiwan University College of Medicine, Taipei, Taiwan., Shen YC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan., Su YC; National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2023 Jun 21; Vol. 14, pp. 1125414. Date of Electronic Publication: 2023 Jun 21 (Print Publication: 2023).
DOI:	10.3389/fphar.2023.1125414
Abstrakt:	The coronavirus disease 2019 (COVID-19) pandemic continues to represent a challenge for public health globally since transmission of different variants of the virus does not seem to be effectively affected by the current treatments and vaccines. During COVID-19 the outbreak in Taiwan, the patients with mild symptoms were improved after the treatment with NRICM101, a traditional Chinese medicine formula developed by our institute. Here, we investigated the effect and mechanism of action of NRICM101 on improval of COVID-19-induced pulmonary injury using S1 subunit of the SARS-CoV-2 spike protein-induced diffuse alveolar damage (DAD) of hACE2 transgenic mice. The S1 protein induced significant pulmonary injury with the hallmarks of DAD (strong exudation, interstitial and intra-alveolar edema, hyaline membranes, abnormal pneumocyte apoptosis, strong leukocyte infiltration, and cytokine production). NRICM101 effectively reduced all of these hallmarks. We then used next-generation sequencing assays to identify 193 genes that were differentially expressed in the S1+NRICM101 group. Of these, three ( Ddit4 , Ikbke , Tnfaip3 ) were significantly represented in the top 30 enriched downregulated gene ontology (GO) terms in the S1+NRICM101 group versus the S1+saline group. These terms included the innate immune response, pattern recognition receptor (PRR), and Toll-like receptor signaling pathways. We found that NRICM101 disrupted the interaction of the spike protein of various SARS-CoV-2 variants with the human ACE2 receptor. It also suppressed the expression of cytokines IL-1β, IL-6, TNF-α, MIP-1β, IP-10, and MIP-1α in alveolar macrophages activated by lipopolysaccharide. We conclude that NRICM101 effectively protects against SARS-CoV-2-S1-induced pulmonary injury via modulation of the innate immune response, pattern recognition receptor, and Toll-like receptor signaling pathways to ameliorate DAD. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Wei, Tsai, Liaw, Chiou, Tseng, Liao, Lin, Chiou, Liou, Yu, Shen and Su.)
Databáze:	MEDLINE
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