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

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.

Taiwan Chingguan Yihau (NRICM101) prevents kainic acid-induced seizures in rats by modulating neuroinflammation and the glutamatergic system

“…These results suggested that the anticonvulsant and neuroprotective effects of NRICM101 might be achieved by suppressing astrocytosis and reducing the levels of in ammatory cytokines. Consistent with our ndings, Lin et al demonstrated that NRICM101 attenuates the in ammatory process in acid intratracheal instillation-induced acute lung injury in mice mainly via a reduction in TNF-α and IL-6; this phenomenon is related to the downregulation of the STAT3 pathway (Lin et al, 2023). Additionally, previous studies demonstrated that NRICM101 attenuates lipopolysaccharide (LPS)-induced production of in ammatory cytokines, e.g., TNF-α, IL-1β, and IL-6, in murine alveolar macrophages (Wei et al, 2013;Tsai et al, 2021).…”

Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II

“…TCM has also contributed to COVID-19 treatment [ 14 , 15 ]. Taiwan Chingguan-Yihau (NRICM101), a TCM formula targeting viral respiratory infection and immunomodulation reported by the National Research Institute of Chinese Medicine, Taiwan (NRICM), has been commonly recommended and was clinically proven to be effective for the treatment of COVID-19 [ 16 , 17 , 18 ]. Based on the theoretical TCM system, the functions of Scutellaria baicalensis ( S. baicalensis ), Houttuynia cordata ( H. cordata ), and Isatis indigotica ( I. indigotica ) in NRICM101 are to clear heat, decrease dampness, promote diuresis, detoxify, and reduce swelling [ 19 , 20 , 21 ].…”