ACE2 and a Traditional Chinese Medicine Formula NRICM101 Could Alleviate the Inflammation and Pathogenic Process of Acute Lung Injury

Cheng-Han Lin; Yi-Ju Chen; Meng-Wei Lin; Ho-Ju Chang; Xin-Rui Yang; Chih-Sheng Lin

doi:10.3390/medicina59091554

ACE2 and a Traditional Chinese Medicine Formula NRICM101 Could Alleviate the Inflammation and Pathogenic Process of Acute Lung Injury

Medicina (Kaunas). 2023 Aug 26;59(9):1554. doi: 10.3390/medicina59091554.

Authors

Cheng-Han Lin¹, Yi-Ju Chen¹, Meng-Wei Lin¹, Ho-Ju Chang¹, Xin-Rui Yang¹, Chih-Sheng Lin^{1

2

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Affiliations

¹ Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan.
² Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan.
³ Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan.

Abstract

COVID-19 is a highly transmittable respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major complication of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6 and TNF-α) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

Keywords: acute lung injury (ALI); angiotensin-converting enzyme type II (ACE2); animal model; traditional Chinese medicine.

Grants and funding

This work was supported by the grants of NSTC 110-2312-B-A49-001-MY3, NSTC 112-2811-B-A49-501, NSTC 112-2811-B-A49-503 and NSTC 112-2321-B-A49-005, from the National Science and Technology Council (NSTC), Taiwan. This work was also financially supported by the “Center for Intelligent Drug Systems and Smart Bio-devices (IDS²B)” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project of the National Yang Ming Chiao Tung University and Ministry of Education (MOE), Taiwan.