In Silico and In Vitro studies of taiwan chingguan yihau (NRICM101) on TNF-α/IL-1β-induced human lung cells

Yih-Dih Cheng; Chi-Cheng Lu; Yuan-Man Hsu; Fuu-Jen Tsai; Da-Tian Bau; Shih-Chang Tsai; Ching-Chang Cheng; Jen-Jyh Lin; Yuang-Yu Huang; Yu-Ning Juan; Yu-Jen Chiu; Sheng-Chu Kuo; Jai-Sing Yang; Lii-Tzu Wu

doi:10.37796/2211-8039.1378

In Silico and In Vitro studies of taiwan chingguan yihau (NRICM101) on TNF-α/IL-1β-induced human lung cells

Biomedicine (Taipei). 2022 Sep 1;12(3):56-71. doi: 10.37796/2211-8039.1378. eCollection 2022.

Authors

Yih-Dih Cheng^{1

2}, Chi-Cheng Lu³, Yuan-Man Hsu^{4

5}, Fuu-Jen Tsai^{6

7

8}, Da-Tian Bau^{9

10

11}, Shih-Chang Tsai¹², Ching-Chang Cheng¹³, Jen-Jyh Lin¹⁴, Yuang-Yu Huang¹⁵, Yu-Ning Juan¹⁵, Yu-Jen Chiu^{16

17

18}, Sheng-Chu Kuo¹, Jai-Sing Yang¹⁵, Lii-Tzu Wu¹⁹

Affiliations

¹ School of Pharmacy, China Medical University, Taichung, 406040, Taiwan.
² Department of Pharmacy, China Medical University Hospital, Taichung, 404327, Taiwan.
³ Department of Sport Performance, National Taiwan University of Sport, Taichung, 404401, Taiwan.
⁴ Department of Biological Science and Technology, College of Life Sciences, China Medical University, Taichung, Taiwan, 406040, Taiwan.
⁵ Department of Animal Science and Biotechnology, Agriculture College, Tunghai University, Taichung, 407224, Taiwan.
⁶ School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404333, Taiwan.
⁷ China Medical University Children's Hospital, Taichung, 404327, Taiwan.
⁸ Department of Medical Genetics, China Medical University Hospital, Taichung, 404327, Taiwan.
⁹ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404333, Taiwan.
¹⁰ Terry Fox Cancer Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, 404327, Taiwan.
¹¹ Department of Bioinformatics and Medical Engineering, Asia University, Taichung, 413305, Taiwan.
¹² Department of Biological Science and Technology, China Medical University, Taichung, 406040, Taiwan.
¹³ Laboratory Animal Service Center, China Medical University, Taichung, 404333, Taiwan.
¹⁴ Division of Cardiology, Department of Medicine, China Medical University Hospital, Taichung, 404327, Taiwan.
¹⁵ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404327, Taiwan.
¹⁶ Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112201, Taiwan.
¹⁷ Department of Surgery, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
¹⁸ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
¹⁹ Department of Microbiology, School of Medicine, China Medical University, Taichung, 404333, Taiwan.

Abstract

COVID-19 pandemic has been a global outbreak of coronavirus (SARS-CoV-2 virus) since 2019. Taiwan Chingguan Yihau (NRICM101) is the first traditional Chinese medicine (TCM) classic herbal formula and is widely used for COVID-19 patients in Taiwan and more than 50 nations. This study is to investigate in silico target fishing for the components of NRICM101 and to explore whether NRICM101 inhibits cytokines-induced normal human lung cell injury in vitro. Our results showed that network prediction of NRICM101 by a high throughput target screening platform showed that NRICM101 has multiple functions that may affect cytokine regulation to prevent human lung cell injury. In addition, NRICM101 revealed protective effects against TNF-α/IL-1β-induced normal human lung HEL 299 cell injury through JNK and p38MAPK kinase signaling. Next-generation sequencing (NGS) analysis of NRICM101 on TNF-α/IL-1β-injured HEL 299 cells indicated that inflammatory pathway, cell movement of macrophages, cellular infiltration by macrophages, and Th1/Th2 immuno-regulation pathways were included. Thus, NRICM101 is a therapeutic agent, and it can improve COVID-19 syndrome to confer beneficial effects through multiple targeting and multiple mechanisms.

Keywords: High throughput target screening platform; Next-generation sequencing (NGS); TNF-α/IL-1β-induced lung cell injury; Taiwan chingguan Yihau (NRICM101); Traditional Chinese medicine (TCM).