Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activity

IntroductionTo investigate the potential anti-hepatitis B virus (HBV) activity of Icariside Ⅱ (ICS Ⅱ), and elucidate its underlying mitochondrial dynamics mechanisms.MethodsThe study employed in vivo and in vitro assays to evaluate anti-HBV effects of ICS Ⅱ. An HBV replicating mouse model was establ...

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Main Authors: Zhengyun Liu, Haiyan Yang, Juan Wen, Dongyan Xiao, Wan Yu, Guo Luo, Qihai Gong, Huan Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1544714/full
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author Zhengyun Liu
Haiyan Yang
Juan Wen
Dongyan Xiao
Dongyan Xiao
Wan Yu
Guo Luo
Qihai Gong
Huan Wang
author_facet Zhengyun Liu
Haiyan Yang
Juan Wen
Dongyan Xiao
Dongyan Xiao
Wan Yu
Guo Luo
Qihai Gong
Huan Wang
author_sort Zhengyun Liu
collection DOAJ
description IntroductionTo investigate the potential anti-hepatitis B virus (HBV) activity of Icariside Ⅱ (ICS Ⅱ), and elucidate its underlying mitochondrial dynamics mechanisms.MethodsThe study employed in vivo and in vitro assays to evaluate anti-HBV effects of ICS Ⅱ. An HBV replicating mouse model was established through hydrodynamic injection of pAAV/HBV1.2, the impact of ICS Ⅱ on HBV replication and liver toxicity was assessed. In vitro cell-based assays used HBV-positive HepG2.2.15 cells. Cytotoxicity was determined with CCK-8 assay, while ELISA and qPCR were employed to measure HBsAg, HBeAg, and HBV DNA levels. The livers of ICS II-treated HBV-infected mice were taken for transcriptome sequencing to screen for different genes, and the results were verified by Western Blot. Mitochondrial morphology and dynamics were visualized using confocal imaging and transmission electron microscopy. Key protein expressions related to mitochondrial fission and fusion were analyzed via WB. Intracellular ROS generation was assessed using fluorescence staining.ResultsThe study found that ICS Ⅱ exhibited significant anti-HBV effects both in vivo and in vitro. The results of RNA-Seq indicated that ICS Ⅱ modulated the mRNA levels of Fisl, a protein associated with mitochondrial dynamics, during the anti-HBV response. It induced mitochondrial fragmentation and enhanced mitochondrial motility in HBV-positive cells. Notably, key proteins associated with mitochondrial fission and fusion demonstrated alterations favoring fission. Furthermore, ICS Ⅱ effectively reduced ROS production in HBV-positive cells.ConclusionICS Ⅱ exhibits significant anti-HBV potential through its regulation of mitochondrial dynamics and ROS production.
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publisher Frontiers Media S.A.
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series Frontiers in Pharmacology
spelling doaj-art-1f7fc0c794a147dfb7830c92a06b37bc2025-08-20T02:53:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15447141544714Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activityZhengyun Liu0Haiyan Yang1Juan Wen2Dongyan Xiao3Dongyan Xiao4Wan Yu5Guo Luo6Qihai Gong7Huan Wang8Key Laboratory of Infectious Disease and Biosafety, Provincial Department of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaKey Laboratory of Infectious Disease and Biosafety, Provincial Department of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaKey Laboratory of Infectious Disease and Biosafety, Provincial Department of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaKey Laboratory of Infectious Disease and Biosafety, Provincial Department of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaDepartment of Basic Teaching, Zunyi Medical and Pharmaceutical College, Zunyi, Guizhou, ChinaKey Laboratory of Infectious Disease and Biosafety, Provincial Department of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaKey Laboratory of Infectious Disease and Biosafety, Provincial Department of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaKey Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaKey Laboratory of Infectious Disease and Biosafety, Provincial Department of Education, Zunyi Medical University, Zunyi, Guizhou, ChinaIntroductionTo investigate the potential anti-hepatitis B virus (HBV) activity of Icariside Ⅱ (ICS Ⅱ), and elucidate its underlying mitochondrial dynamics mechanisms.MethodsThe study employed in vivo and in vitro assays to evaluate anti-HBV effects of ICS Ⅱ. An HBV replicating mouse model was established through hydrodynamic injection of pAAV/HBV1.2, the impact of ICS Ⅱ on HBV replication and liver toxicity was assessed. In vitro cell-based assays used HBV-positive HepG2.2.15 cells. Cytotoxicity was determined with CCK-8 assay, while ELISA and qPCR were employed to measure HBsAg, HBeAg, and HBV DNA levels. The livers of ICS II-treated HBV-infected mice were taken for transcriptome sequencing to screen for different genes, and the results were verified by Western Blot. Mitochondrial morphology and dynamics were visualized using confocal imaging and transmission electron microscopy. Key protein expressions related to mitochondrial fission and fusion were analyzed via WB. Intracellular ROS generation was assessed using fluorescence staining.ResultsThe study found that ICS Ⅱ exhibited significant anti-HBV effects both in vivo and in vitro. The results of RNA-Seq indicated that ICS Ⅱ modulated the mRNA levels of Fisl, a protein associated with mitochondrial dynamics, during the anti-HBV response. It induced mitochondrial fragmentation and enhanced mitochondrial motility in HBV-positive cells. Notably, key proteins associated with mitochondrial fission and fusion demonstrated alterations favoring fission. Furthermore, ICS Ⅱ effectively reduced ROS production in HBV-positive cells.ConclusionICS Ⅱ exhibits significant anti-HBV potential through its regulation of mitochondrial dynamics and ROS production.https://www.frontiersin.org/articles/10.3389/fphar.2025.1544714/fullhepatitis B virusHepG2.2.15 cellmitochondrial dynamicROSreactive oxygen speciesicariside II
spellingShingle Zhengyun Liu
Haiyan Yang
Juan Wen
Dongyan Xiao
Dongyan Xiao
Wan Yu
Guo Luo
Qihai Gong
Huan Wang
Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activity
Frontiers in Pharmacology
hepatitis B virus
HepG2.2.15 cell
mitochondrial dynamic
ROS
reactive oxygen species
icariside II
title Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activity
title_full Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activity
title_fullStr Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activity
title_full_unstemmed Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activity
title_short Icarisid Ⅱ modulates mitochondrial dynamics for anti-HBV activity
title_sort icarisid ii modulates mitochondrial dynamics for anti hbv activity
topic hepatitis B virus
HepG2.2.15 cell
mitochondrial dynamic
ROS
reactive oxygen species
icariside II
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1544714/full
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