NRICM101 ameliorates SARS-CoV-2–S1-induced pulmonary injury in K18-hACE2 mice model
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 w...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1125414/full |
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| author | Wen-Chi Wei Keng-Chang Tsai Keng-Chang Tsai Chia-Ching Liaw Chia-Ching Liaw Chun-Tang Chiou Yu-Hwei Tseng Geng-You Liao Yu-Chi Lin Wen-Fei Chiou Kuo-Tong Liou I-Shing Yu Yuh-Chiang Shen Yi-Chang Su |
| author_facet | Wen-Chi Wei Keng-Chang Tsai Keng-Chang Tsai Chia-Ching Liaw Chia-Ching Liaw Chun-Tang Chiou Yu-Hwei Tseng Geng-You Liao Yu-Chi Lin Wen-Fei Chiou Kuo-Tong Liou I-Shing Yu Yuh-Chiang Shen Yi-Chang Su |
| author_sort | Wen-Chi Wei |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-13T04:04:35Z |
| format | Article |
| id | doaj.art-b868dad646ec45069714c8c3621bd4b5 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T04:04:35Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b868dad646ec45069714c8c3621bd4b52023-06-21T08:38:52ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-06-011410.3389/fphar.2023.11254141125414NRICM101 ameliorates SARS-CoV-2–S1-induced pulmonary injury in K18-hACE2 mice modelWen-Chi Wei0Keng-Chang Tsai1Keng-Chang Tsai2Chia-Ching Liaw3Chia-Ching Liaw4Chun-Tang Chiou5Yu-Hwei Tseng6Geng-You Liao7Yu-Chi Lin8Wen-Fei Chiou9Kuo-Tong Liou10I-Shing Yu11Yuh-Chiang Shen12Yi-Chang Su13National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanPh.D Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanDepartment of Biochemical Science and Technology, National Chiayi University, Chiayi, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanInstitute of Physiology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanLaboratory Animal Center, National Taiwan University College of Medicine, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanNational Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, TaiwanThe 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.https://www.frontiersin.org/articles/10.3389/fphar.2023.1125414/fullCOVID-19NRICM101traditional Chinese medicinelung injurypattern recognition receptors |
| spellingShingle | Wen-Chi Wei Keng-Chang Tsai Keng-Chang Tsai Chia-Ching Liaw Chia-Ching Liaw Chun-Tang Chiou Yu-Hwei Tseng Geng-You Liao Yu-Chi Lin Wen-Fei Chiou Kuo-Tong Liou I-Shing Yu Yuh-Chiang Shen Yi-Chang Su NRICM101 ameliorates SARS-CoV-2–S1-induced pulmonary injury in K18-hACE2 mice model Frontiers in Pharmacology COVID-19 NRICM101 traditional Chinese medicine lung injury pattern recognition receptors |
| title | NRICM101 ameliorates SARS-CoV-2–S1-induced pulmonary injury in K18-hACE2 mice model |
| title_full | NRICM101 ameliorates SARS-CoV-2–S1-induced pulmonary injury in K18-hACE2 mice model |
| title_fullStr | NRICM101 ameliorates SARS-CoV-2–S1-induced pulmonary injury in K18-hACE2 mice model |
| title_full_unstemmed | NRICM101 ameliorates SARS-CoV-2–S1-induced pulmonary injury in K18-hACE2 mice model |
| title_short | NRICM101 ameliorates SARS-CoV-2–S1-induced pulmonary injury in K18-hACE2 mice model |
| title_sort | nricm101 ameliorates sars cov 2 s1 induced pulmonary injury in k18 hace2 mice model |
| topic | COVID-19 NRICM101 traditional Chinese medicine lung injury pattern recognition receptors |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1125414/full |
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