Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 15 July 2023 / Approved: 17 July 2023 / Online: 17 July 2023 (07:32:40 CEST)

A peer-reviewed article of this Preprint also exists.

Lin, C.-H.; Chen, Y.-J.; Lin, M.-W.; Chang, H.-J.; Yang, X.-R.; Lin, C.-S. ACE2 and a Traditional Chinese Medicine Formula NRICM101 Could Alleviate the Inflammation and Pathogenic Process of Acute Lung Injury. Medicina 2023, 59, 1554. Lin, C.-H.; Chen, Y.-J.; Lin, M.-W.; Chang, H.-J.; Yang, X.-R.; Lin, C.-S. ACE2 and a Traditional Chinese Medicine Formula NRICM101 Could Alleviate the Inflammation and Pathogenic Process of Acute Lung Injury. Medicina 2023, 59, 1554.

Abstract

COVID-19 is a highly infectious respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major cause 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, TNF-α, and TGF-β1) 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

Subject

Biology and Life Sciences, Animal Science, Veterinary Science and Zoology

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