Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism

Fibrosis is a pathological hallmark of various chronic diseases and contributes significantly to organ dysfunction and poor clinical outcomes. Despite the availability of antifibrotic agents, their limited efficacy and adverse side effect profiles underscore the urgent need for safer and more effect...

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Main Authors: Jiarui Zhao, Wei Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1619581/full
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author Jiarui Zhao
Wei Zhang
author_facet Jiarui Zhao
Wei Zhang
author_sort Jiarui Zhao
collection DOAJ
description Fibrosis is a pathological hallmark of various chronic diseases and contributes significantly to organ dysfunction and poor clinical outcomes. Despite the availability of antifibrotic agents, their limited efficacy and adverse side effect profiles underscore the urgent need for safer and more effective therapeutic alternatives. Traditional Chinese medicines have emerged as promising candidates for fibrosis management. Epimedium, widely used in traditional Chinese medicine, exhibits notable antifibrotic activity, primarily attributed to its bioactive flavonoid icariin (ICA). However, the clinical application of ICA is hindered by its low bioavailability. Recent advances in extraction methods and drug delivery systems have improved the pharmacokinetic properties of ICA and related active metabolites, including icaritin and icariside II. These metabolites exert antifibrotic effects through multifaceted mechanisms, including anti-inflammatory and antioxidant activities, mitochondrial function modulation, apoptosis regulation, and autophagy. This review summarizes current insights into the molecular pathways through which ICA and related metabolites attenuate fibrosis, thereby supporting their potential for clinical translation in antifibrotic therapy.
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spelling doaj-art-3dc41afc84634b5a9fe1d1fbe4ba5f8a2025-08-20T03:07:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.16195811619581Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanismJiarui ZhaoWei ZhangFibrosis is a pathological hallmark of various chronic diseases and contributes significantly to organ dysfunction and poor clinical outcomes. Despite the availability of antifibrotic agents, their limited efficacy and adverse side effect profiles underscore the urgent need for safer and more effective therapeutic alternatives. Traditional Chinese medicines have emerged as promising candidates for fibrosis management. Epimedium, widely used in traditional Chinese medicine, exhibits notable antifibrotic activity, primarily attributed to its bioactive flavonoid icariin (ICA). However, the clinical application of ICA is hindered by its low bioavailability. Recent advances in extraction methods and drug delivery systems have improved the pharmacokinetic properties of ICA and related active metabolites, including icaritin and icariside II. These metabolites exert antifibrotic effects through multifaceted mechanisms, including anti-inflammatory and antioxidant activities, mitochondrial function modulation, apoptosis regulation, and autophagy. This review summarizes current insights into the molecular pathways through which ICA and related metabolites attenuate fibrosis, thereby supporting their potential for clinical translation in antifibrotic therapy.https://www.frontiersin.org/articles/10.3389/fphar.2025.1619581/fullicariinicariside IIicaritinfibrosispharmacokineticsmolecular mechanism
spellingShingle Jiarui Zhao
Wei Zhang
Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism
Frontiers in Pharmacology
icariin
icariside II
icaritin
fibrosis
pharmacokinetics
molecular mechanism
title Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism
title_full Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism
title_fullStr Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism
title_full_unstemmed Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism
title_short Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism
title_sort icariin and related metabolites in fibrosis management pharmacological properties and molecular mechanism
topic icariin
icariside II
icaritin
fibrosis
pharmacokinetics
molecular mechanism
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1619581/full
work_keys_str_mv AT jiaruizhao icariinandrelatedmetabolitesinfibrosismanagementpharmacologicalpropertiesandmolecularmechanism
AT weizhang icariinandrelatedmetabolitesinfibrosismanagementpharmacologicalpropertiesandmolecularmechanism