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. 2020 Jun 19;9(6):770.
doi: 10.3390/plants9060770.

Geranium and Lemon Essential Oils and Their Active Compounds Downregulate Angiotensin-Converting Enzyme 2 (ACE2), a SARS-CoV-2 Spike Receptor-Binding Domain, in Epithelial Cells

K J Senthil Kumar  1 , M Gokila Vani  1 , Chung-Shuan Wang  1 , Chia-Chi Chen  2 , Yu-Chien Chen  2 , Li-Ping Lu  2 , Ching-Hsiang Huang  2 , Chien-Sing Lai  1 , Sheng-Yang Wang  1   3
Affiliations

Geranium and Lemon Essential Oils and Their Active Compounds Downregulate Angiotensin-Converting Enzyme 2 (ACE2), a SARS-CoV-2 Spike Receptor-Binding Domain, in Epithelial Cells

K J Senthil Kumar et al. Plants (Basel). .

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease-2019 (COVID-19), is a pandemic disease that has been declared as modern history's gravest health emergency worldwide. Until now, no precise treatment modality has been developed. The angiotensin-converting enzyme 2 (ACE2) receptor, a host cell receptor, has been found to play a crucial role in virus cell entry; therefore, ACE2 blockers can be a potential target for anti-viral intervention. In this study, we evaluated the ACE2 inhibitory effects of 10 essential oils. Among them, geranium and lemon oils displayed significant ACE2 inhibitory effects in epithelial cells. In addition, immunoblotting and qPCR analysis also confirmed that geranium and lemon oils possess potent ACE2 inhibitory effects. Furthermore, the gas chromatography-mass spectrometry (GC-MS) analysis displayed 22 compounds in geranium oil and 9 compounds in lemon oil. Citronellol, geraniol, and neryl acetate were the major compounds of geranium oil and limonene that represented major compound of lemon oil. Next, we found that treatment with citronellol and limonene significantly downregulated ACE2 expression in epithelial cells. The results suggest that geranium and lemon essential oils and their derivative compounds are valuable natural anti-viral agents that may contribute to the prevention of the invasion of SARS-CoV-2/COVID-19 into the human body.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; citronellol; geranium essential oil; lemon essential oil; limonene.

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Conflict of interest statement

The authors declare that there is no conflict of interest. The company provides no financial support for the research of this article. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Essential oils reduced human angiotensin-converting enzyme 2 (ACE2) levels in HT-29 cells. (A) The ACE2 inhibitory effects of selected essential oils. HT-29 cells were incubated with indicated concentration of selected essential oils for 48 h. Cell lysates were subjected to determine ACE2 levels using a commercially available ELISA kit. (B,C) The dose-dependent inhibitory effects of geranium and lemon essential oils were determined in the same course of time. Values represent the mean ± SD of three independent experiments. p-values of less than 0.05 *, 0.01 **, 0.001 ***, and 0.0001 **** were considered statistically significant for the sample treatment group vs. the control group.
Figure 2
Figure 2
Geranium and lemon essential oils downregulated ACE2 expression in HT-29 cells. (A) Protein expression levels of ACE2 were determined by immunoblotting. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as an internal loading control. Relative density of one representative experiment is shown, where ACE2 signal was normalized to GAPDH signal. (B,C) Relative expression of ACE2 and TMPRSS2 mRNAs in HT-29 cells. Total RNA was extracted from cells treated with indicated concentration of geranium and lemon essential oils for 48 h. The transcription levels of ACE2 and TMPRSS2 were quantified by qPCR and a representative experiment is shown. The Δct values of ACE2 and TMPRSS2 mRNAs were normalized to GAPDH mRNA. Values represent the mean ± SD of three independent experiments. p-values of less than 0.01 **, and 0.001 *** were considered statistically significant for the sample treatment group vs. the control group.
Figure 3
Figure 3
GC–MS analysis of geranium and lemon essential oils. GC profiles and chemical structures of the major compounds in geranium (A) and lemon (B) essential oils.
Figure 4
Figure 4
ACE2 inhibitory effects of major compounds of geranium and lemon essential oils. (A) ACE2 activity in HT-29 cells were determined by ELISA assay. (B) Protein expression levels of ACE2 were determined by immunoblotting. Relative density of one representative experiment is shown, where ACE2 signal was normalized to GAPDH signal. (C,D) Relative expression of ACE2 and TMPRSS2 mRNAs in HT-29 cells. Values represent the mean ± SD of three independent experiments. p-values of less than 0.05 *, 0.01 **, 0.001 ***, and 0.0001 **** were considered statistically significant for the sample treatment group vs. the control group.
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