<i>Melastoma malabathricum</i> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection
Platelet hyper-reactivity and neutrophil extracellular trap (NET) formation contribute to the development of thromboembolic diseases for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the pathophysiological effects of SARS-CoV-2 surface p...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Pathogens |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-0817/12/2/341 |
| _version_ | 1797618846142562304 |
|---|---|
| author | Tse-Hung Huang Pei-Wen Hsieh Tsu-Jung Chen Hui-Ju Tsai Ju-Chien Cheng Hsiang-Ruei Liao Shun-Li Kuo Ching-Ping Tseng |
| author_facet | Tse-Hung Huang Pei-Wen Hsieh Tsu-Jung Chen Hui-Ju Tsai Ju-Chien Cheng Hsiang-Ruei Liao Shun-Li Kuo Ching-Ping Tseng |
| author_sort | Tse-Hung Huang |
| collection | DOAJ |
| description | Platelet hyper-reactivity and neutrophil extracellular trap (NET) formation contribute to the development of thromboembolic diseases for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the pathophysiological effects of SARS-CoV-2 surface protein components and the viral double-stranded RNA (dsRNA) on platelet aggregation and NET formation. Traditional Chinese medicine (TCM) with anti-viral effects was also delineated. The treatment of human washed platelets with SARS-CoV-2 spike protein S1 or the ectodomain S1 + S2 regions neither caused platelet aggregation nor enhanced agonists-stimulated platelet aggregation. Moreover, NET formation can be induced by polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of viral dsRNA, but not by the pseudovirus composed of SARS-CoV-2 spike, envelope, and membrane proteins. To search for TCM with anti-NET activity, the plant <i>Melastoma malabathricum</i> L. which has anticoagulant activity was partially purified by fractionation. One of the fractions inhibited poly(I:C)-induced NET formation in a dose-dependent manner. This study implicates that SARS-CoV-2 structural proteins alone are not sufficient to promote NET and platelet activation. Instead, dsRNA formed during viral replication stimulates NET formation. This study also sheds new insight into using the active components of <i>Melastoma malabathricum</i> L. with anti-NET activity in the battle of thromboembolic diseases associated with SARS-CoV-2 infection. |
| first_indexed | 2024-03-11T08:18:23Z |
| format | Article |
| id | doaj.art-dda5a64cff7d42299d4951ac3b058e22 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-11T08:18:23Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-dda5a64cff7d42299d4951ac3b058e222023-11-16T22:35:18ZengMDPI AGPathogens2076-08172023-02-0112234110.3390/pathogens12020341<i>Melastoma malabathricum</i> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 InfectionTse-Hung Huang0Pei-Wen Hsieh1Tsu-Jung Chen2Hui-Ju Tsai3Ju-Chien Cheng4Hsiang-Ruei Liao5Shun-Li Kuo6Ching-Ping Tseng7Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung 204, TaiwanResearch Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan 333, TaiwanDepartment of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDepartment of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDepartment of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, TaiwanGraduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanSchool of Traditional Chinese Medicine, Chang Gung University, Taoyuan 333, TaiwanGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanPlatelet hyper-reactivity and neutrophil extracellular trap (NET) formation contribute to the development of thromboembolic diseases for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the pathophysiological effects of SARS-CoV-2 surface protein components and the viral double-stranded RNA (dsRNA) on platelet aggregation and NET formation. Traditional Chinese medicine (TCM) with anti-viral effects was also delineated. The treatment of human washed platelets with SARS-CoV-2 spike protein S1 or the ectodomain S1 + S2 regions neither caused platelet aggregation nor enhanced agonists-stimulated platelet aggregation. Moreover, NET formation can be induced by polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of viral dsRNA, but not by the pseudovirus composed of SARS-CoV-2 spike, envelope, and membrane proteins. To search for TCM with anti-NET activity, the plant <i>Melastoma malabathricum</i> L. which has anticoagulant activity was partially purified by fractionation. One of the fractions inhibited poly(I:C)-induced NET formation in a dose-dependent manner. This study implicates that SARS-CoV-2 structural proteins alone are not sufficient to promote NET and platelet activation. Instead, dsRNA formed during viral replication stimulates NET formation. This study also sheds new insight into using the active components of <i>Melastoma malabathricum</i> L. with anti-NET activity in the battle of thromboembolic diseases associated with SARS-CoV-2 infection.https://www.mdpi.com/2076-0817/12/2/341double-stranded RNAneutrophil extracellular trapplatelet aggregationSARS-CoV-2 infectiontraditional Chinese medicine |
| spellingShingle | Tse-Hung Huang Pei-Wen Hsieh Tsu-Jung Chen Hui-Ju Tsai Ju-Chien Cheng Hsiang-Ruei Liao Shun-Li Kuo Ching-Ping Tseng <i>Melastoma malabathricum</i> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection Pathogens double-stranded RNA neutrophil extracellular trap platelet aggregation SARS-CoV-2 infection traditional Chinese medicine |
| title | <i>Melastoma malabathricum</i> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection |
| title_full | <i>Melastoma malabathricum</i> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection |
| title_fullStr | <i>Melastoma malabathricum</i> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection |
| title_full_unstemmed | <i>Melastoma malabathricum</i> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection |
| title_short | <i>Melastoma malabathricum</i> L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection |
| title_sort | i melastoma malabathricum i l suppresses neutrophil extracellular trap formation induced by synthetic analog of viral double stranded rna associated with sars cov 2 infection |
| topic | double-stranded RNA neutrophil extracellular trap platelet aggregation SARS-CoV-2 infection traditional Chinese medicine |
| url | https://www.mdpi.com/2076-0817/12/2/341 |
| work_keys_str_mv | AT tsehunghuang imelastomamalabathricumilsuppressesneutrophilextracellulartrapformationinducedbysyntheticanalogofviraldoublestrandedrnaassociatedwithsarscov2infection AT peiwenhsieh imelastomamalabathricumilsuppressesneutrophilextracellulartrapformationinducedbysyntheticanalogofviraldoublestrandedrnaassociatedwithsarscov2infection AT tsujungchen imelastomamalabathricumilsuppressesneutrophilextracellulartrapformationinducedbysyntheticanalogofviraldoublestrandedrnaassociatedwithsarscov2infection AT huijutsai imelastomamalabathricumilsuppressesneutrophilextracellulartrapformationinducedbysyntheticanalogofviraldoublestrandedrnaassociatedwithsarscov2infection AT juchiencheng imelastomamalabathricumilsuppressesneutrophilextracellulartrapformationinducedbysyntheticanalogofviraldoublestrandedrnaassociatedwithsarscov2infection AT hsiangrueiliao imelastomamalabathricumilsuppressesneutrophilextracellulartrapformationinducedbysyntheticanalogofviraldoublestrandedrnaassociatedwithsarscov2infection AT shunlikuo imelastomamalabathricumilsuppressesneutrophilextracellulartrapformationinducedbysyntheticanalogofviraldoublestrandedrnaassociatedwithsarscov2infection AT chingpingtseng imelastomamalabathricumilsuppressesneutrophilextracellulartrapformationinducedbysyntheticanalogofviraldoublestrandedrnaassociatedwithsarscov2infection |