Anisomeles indica Extracts and Their Constituents Suppress the Protein Expression of ACE2 and TMPRSS2 In Vivo and In Vitro

Int J Mol Sci. 2023 Oct 11;24(20):15062. doi: 10.3390/ijms242015062.

Abstract

Coronavirus disease 2019 (COVID-19), stemming from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact. This highly contagious pneumonia remains a significant ongoing threat. Uncertainties persist about the virus's effects on human health, underscoring the need for treatments and prevention. Current research highlights angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key targets against SARS-CoV-2. The virus relies on ACE2 to enter cells and TMPRSS2 to activate its spike protein. Inhibiting ACE2 and TMPRSS2 expression can help prevent and treat SARS-CoV-2 infections. Anisomeles indica (L.) Kuntze, a medicinal plant in traditional Chinese medicine, shows various promising pharmacological properties. In this study, ethanolic extracts of A. indica were examined both in vivo (250 and 500 μM) and in vitro (500 μM). Through Western blotting analysis, a significant reduction in the expression levels of ACE2 and TMPRSS2 proteins was observed in HepG2 (human hepatocellular carcinoma) cells and HEK 293T (human embryonic kidney) cell lines without inducing cellular damage. The principal constituents of A. indica, namely, ovatodiolide (5 and 10 μM), anisomlic acid (5 and 10 μM), and apigenin (12.5 and 25 μM), were also found to produce the same effect. Furthermore, immunohistochemical analysis of mouse liver, kidney, and lung tissues demonstrated a decrease in ACE2 and TMPRSS2 protein expression levels. Consequently, this article suggests that A. indica and its constituents have the potential to reduce ACE2 and TMPRSS2 protein expression levels, thus aiding in the prevention of SARS-CoV-2 infections.

Keywords: ACE2; Anisomeles indica; SARS-CoV-2; TMPRSS2; anisomlic acid; apigenin; ovatodiolide.

MeSH terms

  • Angiotensin-Converting Enzyme 2* / metabolism
  • Animals
  • COVID-19* / metabolism
  • Humans
  • Lung / metabolism
  • Mice
  • Protein Processing, Post-Translational
  • SARS-CoV-2 / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism

Substances

  • Angiotensin-Converting Enzyme 2
  • TMPRSS2 protein, human
  • Serine Endopeptidases

Grants and funding

This research received no external funding.