Anti-Influenza A Virus Activity of <i>Rhododendron brachycarpum</i> Extract and Identification of Hyperoside as the Active Constituent

Influenza A virus (IAV) poses significant public health challenges due to its rapid mutation and drug resistance, necessitating novel antiviral strategies. <i>Rhododendron brachycarpum</i>, traditionally employed in folk medicine to treat inflammatory conditions, contains bioactive flavo...

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Main Authors: Yung Hun Park, Soo Yong Shin, Hayeong Choi, Jae Hyeok Lee, You Jin Kim, Seong Ji Woo, Wonkyun Ronny Im, Sung Ho Jeon
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Microbiology Research
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Online Access:https://www.mdpi.com/2036-7481/16/6/132
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author Yung Hun Park
Soo Yong Shin
Hayeong Choi
Jae Hyeok Lee
You Jin Kim
Seong Ji Woo
Wonkyun Ronny Im
Sung Ho Jeon
author_facet Yung Hun Park
Soo Yong Shin
Hayeong Choi
Jae Hyeok Lee
You Jin Kim
Seong Ji Woo
Wonkyun Ronny Im
Sung Ho Jeon
author_sort Yung Hun Park
collection DOAJ
description Influenza A virus (IAV) poses significant public health challenges due to its rapid mutation and drug resistance, necessitating novel antiviral strategies. <i>Rhododendron brachycarpum</i>, traditionally employed in folk medicine to treat inflammatory conditions, contains bioactive flavonoids with potential antiviral effects. In this study, we investigated the anti-influenza activity of <i>R. brachycarpum</i> leaf extract and identified hyperoside (quercetin-3-O-galactoside) as the active constituent. The crude extract and its n-butanol fraction markedly reduced IAV replication in Madin–Darby canine kidney (MDCK) cells, with IC50/CC50 values of 74.51/201.09 μg/mL and 24.5/113.1 μg/mL, respectively. Hyperoside, purified via bioactivity-guided fractionation and HPLC analysis, demonstrated potent antiviral activity, with an IC50 of 66.59 μM (30.92 μg/mL) and a CC50 of 318.9 μM (148.1 μg/mL), indicating a favorable selectivity index. It significantly suppressed viral mRNA and protein expression in infected cells. Time-of-addition and hemagglutination inhibition assays suggested that hyperoside exerts antiviral effects during early infection stages, likely interfering with viral entry. In silico molecular docking analysis further supported this mechanism, revealing that hyperoside binds strongly to the receptor-binding domain of hemagglutinin (−11.5 kcal/mol), potentially blocking viral attachment. These findings reveal that hyperoside is a major antiviral component of <i>R. brachycarpum</i> and underscore its therapeutic potential as a natural antiviral candidate against IAV infections.
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spelling doaj-art-914907fdf041441a87af5675c17ee31f2025-08-20T03:29:48ZengMDPI AGMicrobiology Research2036-74812025-06-0116613210.3390/microbiolres16060132Anti-Influenza A Virus Activity of <i>Rhododendron brachycarpum</i> Extract and Identification of Hyperoside as the Active ConstituentYung Hun Park0Soo Yong Shin1Hayeong Choi2Jae Hyeok Lee3You Jin Kim4Seong Ji Woo5Wonkyun Ronny Im6Sung Ho Jeon7Department of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Republic of KoreaDepartment of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon 24252, Republic of KoreaInfluenza A virus (IAV) poses significant public health challenges due to its rapid mutation and drug resistance, necessitating novel antiviral strategies. <i>Rhododendron brachycarpum</i>, traditionally employed in folk medicine to treat inflammatory conditions, contains bioactive flavonoids with potential antiviral effects. In this study, we investigated the anti-influenza activity of <i>R. brachycarpum</i> leaf extract and identified hyperoside (quercetin-3-O-galactoside) as the active constituent. The crude extract and its n-butanol fraction markedly reduced IAV replication in Madin–Darby canine kidney (MDCK) cells, with IC50/CC50 values of 74.51/201.09 μg/mL and 24.5/113.1 μg/mL, respectively. Hyperoside, purified via bioactivity-guided fractionation and HPLC analysis, demonstrated potent antiviral activity, with an IC50 of 66.59 μM (30.92 μg/mL) and a CC50 of 318.9 μM (148.1 μg/mL), indicating a favorable selectivity index. It significantly suppressed viral mRNA and protein expression in infected cells. Time-of-addition and hemagglutination inhibition assays suggested that hyperoside exerts antiviral effects during early infection stages, likely interfering with viral entry. In silico molecular docking analysis further supported this mechanism, revealing that hyperoside binds strongly to the receptor-binding domain of hemagglutinin (−11.5 kcal/mol), potentially blocking viral attachment. These findings reveal that hyperoside is a major antiviral component of <i>R. brachycarpum</i> and underscore its therapeutic potential as a natural antiviral candidate against IAV infections.https://www.mdpi.com/2036-7481/16/6/132natural productsinfluenza A virusanti-virushyperosidehemagglutinin
spellingShingle Yung Hun Park
Soo Yong Shin
Hayeong Choi
Jae Hyeok Lee
You Jin Kim
Seong Ji Woo
Wonkyun Ronny Im
Sung Ho Jeon
Anti-Influenza A Virus Activity of <i>Rhododendron brachycarpum</i> Extract and Identification of Hyperoside as the Active Constituent
Microbiology Research
natural products
influenza A virus
anti-virus
hyperoside
hemagglutinin
title Anti-Influenza A Virus Activity of <i>Rhododendron brachycarpum</i> Extract and Identification of Hyperoside as the Active Constituent
title_full Anti-Influenza A Virus Activity of <i>Rhododendron brachycarpum</i> Extract and Identification of Hyperoside as the Active Constituent
title_fullStr Anti-Influenza A Virus Activity of <i>Rhododendron brachycarpum</i> Extract and Identification of Hyperoside as the Active Constituent
title_full_unstemmed Anti-Influenza A Virus Activity of <i>Rhododendron brachycarpum</i> Extract and Identification of Hyperoside as the Active Constituent
title_short Anti-Influenza A Virus Activity of <i>Rhododendron brachycarpum</i> Extract and Identification of Hyperoside as the Active Constituent
title_sort anti influenza a virus activity of i rhododendron brachycarpum i extract and identification of hyperoside as the active constituent
topic natural products
influenza A virus
anti-virus
hyperoside
hemagglutinin
url https://www.mdpi.com/2036-7481/16/6/132
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