Melastoma malabathricum L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection

Tse-Hung Huang; Pei-Wen Hsieh; Tsu-Jung Chen; Hui-Ju Tsai; Ju-Chien Cheng; Hsiang-Ruei Liao; Shun-Li Kuo; Ching-Ping Tseng

doi:10.3390/pathogens12020341

Melastoma malabathricum L. Suppresses Neutrophil Extracellular Trap Formation Induced by Synthetic Analog of Viral Double-Stranded RNA Associated with SARS-CoV-2 Infection

Pathogens. 2023 Feb 17;12(2):341. doi: 10.3390/pathogens12020341.

Authors

Tse-Hung Huang^{1

2

3

4}, Pei-Wen Hsieh^{3

5

6

7}, Tsu-Jung Chen⁸, Hui-Ju Tsai⁸, Ju-Chien Cheng⁹, Hsiang-Ruei Liao^{5

6

10}, Shun-Li Kuo^{2

11

12}, Ching-Ping Tseng^{6

8

13}

Affiliations

¹ Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan.
² School of Traditional Chinese Medicine, Chang Gung University, Taoyuan 333, Taiwan.
³ Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
⁴ Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
⁵ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁶ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁷ Department of General Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
⁸ Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
⁹ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan.
¹⁰ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
¹¹ Division of Chinese Medicine Obstetrics and Gynecology, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan.
¹² Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
¹³ Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.

Abstract

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 Melastoma malabathricum 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 Melastoma malabathricum L. with anti-NET activity in the battle of thromboembolic diseases associated with SARS-CoV-2 infection.

Keywords: SARS-CoV-2 infection; double-stranded RNA; neutrophil extracellular trap; platelet aggregation; traditional Chinese medicine.

Abstract

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