Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2

Outbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. GB-1, the herbal formula from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, is used for the prophylaxis of SARS-CoV-2 in Taiwan. In this study, we investigated that the effect of GB-1 and...

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Main Authors: Ching-Yuan Wu, Yu-Shih Lin, Yao-Hsu Yang, Li-Hsin Shu, Yu-Ching Cheng, Hung Te Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-12-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2020.584158/full
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author Ching-Yuan Wu
Ching-Yuan Wu
Yu-Shih Lin
Yao-Hsu Yang
Yao-Hsu Yang
Yao-Hsu Yang
Li-Hsin Shu
Yu-Ching Cheng
Hung Te Liu
author_facet Ching-Yuan Wu
Ching-Yuan Wu
Yu-Shih Lin
Yao-Hsu Yang
Yao-Hsu Yang
Yao-Hsu Yang
Li-Hsin Shu
Yu-Ching Cheng
Hung Te Liu
author_sort Ching-Yuan Wu
collection DOAJ
description Outbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. GB-1, the herbal formula from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, is used for the prophylaxis of SARS-CoV-2 in Taiwan. In this study, we investigated that the effect of GB-1 and the index compounds of GB-1 on the ACE2 and TMPRSS2 expression through in vitro and in vivo study. In our result, GB-1 can inhibit ACE2 and TMPRSS2 protein expression in HepG2 cells, 293T cells, and Caco-2 cells without cytotoxicity. For the mouse model, GB-1 treatment could decrease ACE2 and TMPRSS2 expression levels of the lung and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity. In the compositions of GB-1, 0.5–1 mg/ml of Glycyrrhiza uralensis Fisch. ex DC. extract could not inhibit ACE2 mRNA and protein expression in HepG2 cells. In addition, theaflavin-3-gallate could inhibit protein expression of ACE2 and TMPRSS2 without significant cytotoxicity. Our results suggest that GB-1 and theaflavin-3-gallate could act as potential candidates for prophylaxis or treatment of SARS-CoV-2 infection through inhibiting protein expression of ACE2 and TMPRSS2 for the further study.
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spelling doaj.art-eae70c415fd545aaa00db5e194ec7c0a2022-12-21T18:53:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-12-011110.3389/fphar.2020.584158584158Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2Ching-Yuan Wu0Ching-Yuan Wu1Yu-Shih Lin2Yao-Hsu Yang3Yao-Hsu Yang4Yao-Hsu Yang5Li-Hsin Shu6Yu-Ching Cheng7Hung Te Liu8Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, TaiwanSchool of Chinese Medicine, College of Medicine, Chang Gung University, Chiayi, TaiwanDepartment of Pharmacy, Chiayi Chang Gung Memorial Hospital, Chiayi, TaiwanDepartment of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, TaiwanSchool of Chinese Medicine, College of Medicine, Chang Gung University, Chiayi, TaiwanHealth Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, TaiwanDepartment of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, TaiwanDepartment of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, TaiwanDepartment of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, TaiwanOutbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. GB-1, the herbal formula from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, is used for the prophylaxis of SARS-CoV-2 in Taiwan. In this study, we investigated that the effect of GB-1 and the index compounds of GB-1 on the ACE2 and TMPRSS2 expression through in vitro and in vivo study. In our result, GB-1 can inhibit ACE2 and TMPRSS2 protein expression in HepG2 cells, 293T cells, and Caco-2 cells without cytotoxicity. For the mouse model, GB-1 treatment could decrease ACE2 and TMPRSS2 expression levels of the lung and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity. In the compositions of GB-1, 0.5–1 mg/ml of Glycyrrhiza uralensis Fisch. ex DC. extract could not inhibit ACE2 mRNA and protein expression in HepG2 cells. In addition, theaflavin-3-gallate could inhibit protein expression of ACE2 and TMPRSS2 without significant cytotoxicity. Our results suggest that GB-1 and theaflavin-3-gallate could act as potential candidates for prophylaxis or treatment of SARS-CoV-2 infection through inhibiting protein expression of ACE2 and TMPRSS2 for the further study.https://www.frontiersin.org/articles/10.3389/fphar.2020.584158/fullSARS-CoV-2ACE2TMPRSStheaflavin 3-gallatetheaflavin(+)-catechin 4
spellingShingle Ching-Yuan Wu
Ching-Yuan Wu
Yu-Shih Lin
Yao-Hsu Yang
Yao-Hsu Yang
Yao-Hsu Yang
Li-Hsin Shu
Yu-Ching Cheng
Hung Te Liu
Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2
Frontiers in Pharmacology
SARS-CoV-2
ACE2
TMPRSS
theaflavin 3-gallate
theaflavin
(+)-catechin 4
title Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2
title_full Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2
title_fullStr Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2
title_full_unstemmed Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2
title_short Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2
title_sort potential simultaneous inhibitors of angiotensin converting enzyme 2 and transmembrane protease serine 2
topic SARS-CoV-2
ACE2
TMPRSS
theaflavin 3-gallate
theaflavin
(+)-catechin 4
url https://www.frontiersin.org/articles/10.3389/fphar.2020.584158/full
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