A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuries

Objective: Cerebral ischemia-reperfusion injury (CI/RI) can lead to a range of impairments and even permanent disability.. This systematic review was designed to comprehensively investigate the biological effects of silymarin and silibinin in mitigating CI/RI.Materials and Methods: To find studies p...

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Main Authors: Hossein Mardani-Nafchi, Saeid Heidari-Soureshjani, Sahar Rostamian
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2025-07-01
Series:Avicenna Journal of Phytomedicine
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Online Access:https://ajp.mums.ac.ir/article_25370_0ad2efeb9d54ee881e6e4e4d8ebb9728.pdf
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author Hossein Mardani-Nafchi
Saeid Heidari-Soureshjani
Sahar Rostamian
author_facet Hossein Mardani-Nafchi
Saeid Heidari-Soureshjani
Sahar Rostamian
author_sort Hossein Mardani-Nafchi
collection DOAJ
description Objective: Cerebral ischemia-reperfusion injury (CI/RI) can lead to a range of impairments and even permanent disability.. This systematic review was designed to comprehensively investigate the biological effects of silymarin and silibinin in mitigating CI/RI.Materials and Methods: To find studies published before January 02, 2024, a comprehensive electronic search was carried out across multiple databases, including Cochrane Library, PubMed, Embase, Web of Science, and Scopus. Data including study characteristics, methods, and biological mechanisms were extracted.Results: Silymarin and silibinin potentially improved endogenous antioxidants and reduced lipid peroxidation, nitric oxide (NO), and malondialdehyde (MDA) levels. They also enhances the nuclear factor erythroid 2-related factor 2 (Nrf2) expression and upregulated HO-1 and NAD(P)H: quinone oxidoreductase 1 (NQO1). They also protected the activity of Na+–K+ ATPase, activating mitochondrial membrane potential that suppresses mitochondrial permeability transition pores (mPTP). Moreover, they upregulated proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), uncoupling protein 2 (UCP2), nuclear respiratory factor 1 (NRF1), and reduced inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), and myeloperoxidase (MPO) expression. They inhibited transcription factors, including nuclear factor-kappa B (NF-κB) and IκB-α degradation. They also attenuated tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. Anti-apoptotic properties were revealed by increasing protein Bcl-2 and reducing p53, Bax, caspase-3, and 9 expressions. silymarin improves pathological changes, behavioral tests, and decreases cerebral infarct size.Conclusion: Silymarin and silibinin indicated promising effects on CI/RI through various mechanisms. However, well-designed clinical trials are needed to validate these findings in human subjects.
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spelling doaj-art-fa4d2f59e1d5491c9ffcb37a1af94dfc2025-08-20T02:48:05ZengMashhad University of Medical SciencesAvicenna Journal of Phytomedicine2228-79302228-79492025-07-011541279129710.22038/ajp.2024.2537025370A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuriesHossein Mardani-Nafchi0Saeid Heidari-Soureshjani1Sahar Rostamian2Ph.D. Student of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, IranHarvard Medical School, Department of Medicine, USA.Objective: Cerebral ischemia-reperfusion injury (CI/RI) can lead to a range of impairments and even permanent disability.. This systematic review was designed to comprehensively investigate the biological effects of silymarin and silibinin in mitigating CI/RI.Materials and Methods: To find studies published before January 02, 2024, a comprehensive electronic search was carried out across multiple databases, including Cochrane Library, PubMed, Embase, Web of Science, and Scopus. Data including study characteristics, methods, and biological mechanisms were extracted.Results: Silymarin and silibinin potentially improved endogenous antioxidants and reduced lipid peroxidation, nitric oxide (NO), and malondialdehyde (MDA) levels. They also enhances the nuclear factor erythroid 2-related factor 2 (Nrf2) expression and upregulated HO-1 and NAD(P)H: quinone oxidoreductase 1 (NQO1). They also protected the activity of Na+–K+ ATPase, activating mitochondrial membrane potential that suppresses mitochondrial permeability transition pores (mPTP). Moreover, they upregulated proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), uncoupling protein 2 (UCP2), nuclear respiratory factor 1 (NRF1), and reduced inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), and myeloperoxidase (MPO) expression. They inhibited transcription factors, including nuclear factor-kappa B (NF-κB) and IκB-α degradation. They also attenuated tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. Anti-apoptotic properties were revealed by increasing protein Bcl-2 and reducing p53, Bax, caspase-3, and 9 expressions. silymarin improves pathological changes, behavioral tests, and decreases cerebral infarct size.Conclusion: Silymarin and silibinin indicated promising effects on CI/RI through various mechanisms. However, well-designed clinical trials are needed to validate these findings in human subjects.https://ajp.mums.ac.ir/article_25370_0ad2efeb9d54ee881e6e4e4d8ebb9728.pdfsilymarin carsil silybin ischemiareperfusion injury reperfusion injury
spellingShingle Hossein Mardani-Nafchi
Saeid Heidari-Soureshjani
Sahar Rostamian
A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuries
Avicenna Journal of Phytomedicine
silymarin carsil silybin ischemia
reperfusion injury reperfusion injury
title A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuries
title_full A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuries
title_fullStr A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuries
title_full_unstemmed A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuries
title_short A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuries
title_sort systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia reperfusion injuries
topic silymarin carsil silybin ischemia
reperfusion injury reperfusion injury
url https://ajp.mums.ac.ir/article_25370_0ad2efeb9d54ee881e6e4e4d8ebb9728.pdf
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