Mechanistic Insights Into the Hepatoprotective Effects of Punicalagin Against Oxidative Stress: Involvement of the PI3K/AKT/mTOR Pathway and Autophagy.
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| Title: | Mechanistic Insights Into the Hepatoprotective Effects of Punicalagin Against Oxidative Stress: Involvement of the PI3K/AKT/mTOR Pathway and Autophagy. |
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| Authors: | Yang, Xia1 (AUTHOR), Xiong, Chuan1 (AUTHOR), Zhang, Jing1 (AUTHOR), Chen, Qinqin1 (AUTHOR), Tang, Yunzhao1 (AUTHOR), Fu, Ziwei1 (AUTHOR), Cai, Dachuan1 (AUTHOR), Luo, Qiang1 (AUTHOR) qiangluo@hospital.cqmu.edu.cn, Bose, Anupama1 (AUTHOR) abose@wiley.com |
| Source: | Journal of Food Biochemistry. 5/30/2026, Vol. 2026, p1-15. 15p. |
| Subjects: | PI3K/AKT/mTOR pathway, Autophagy, Mitochondria, Oxidative stress, Pomegranate, Apoptosis, Liver injuries |
| Abstract: | Punicalagin, a major ellagitannin enriched in pomegranate (Punica granatum L.) peel, has been implicated in cellular redox regulation, yet its integrated mechanism against oxidative hepatocellular injury remains insufficiently defined. Here, we combined network pharmacology, molecular docking, and in vitro validation to elucidate the protective actions of punicalagin against hydrogen peroxide (H2O2)–induced injury in HepG2 cells. Punicalagin pretreatment markedly improved cell viability and suppressed intracellular reactive oxygen species accumulation following oxidative challenge. This protection was associated with improved mitochondrial function. Flow cytometry further demonstrated that punicalagin attenuated H2O2‐triggered apoptosis, consistent with modulation of the mitochondrial apoptotic cascade as evidenced by an increased Bcl‐2/Bax balance and reduced caspase‐3 activation. Punicalagin also enhanced autophagy, as indicated by increased LC3B‐II and decreased p62. Network pharmacology identified overlapping targets between punicalagin and liver injury, with enrichment analyses highlighting PI3K/AKT‐related signaling; docking predicted favorable binding of punicalagin to AKT1. Mechanistically, punicalagin blunted oxidative stress–induced phosphorylation of PI3K, AKT, and mTOR without altering total protein abundance. Importantly, pharmacological reactivation of AKT using SC79 mitigated punicalagin‐induced autophagy, supporting a pathway‐dependent mode of action. Collectively, these findings indicate that punicalagin alleviates oxidative hepatocellular injury, supporting its potential as a food‐derived bioactive for oxidative stress–related liver dysfunction. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Food Biochemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
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| Header | DbId: egs DbLabel: Engineering Source An: 194208991 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Mechanistic Insights Into the Hepatoprotective Effects of Punicalagin Against Oxidative Stress: Involvement of the PI3K/AKT/mTOR Pathway and Autophagy. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Yang%2C+Xia%22">Yang, Xia</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Xiong%2C+Chuan%22">Xiong, Chuan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Jing%22">Zhang, Jing</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chen%2C+Qinqin%22">Chen, Qinqin</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tang%2C+Yunzhao%22">Tang, Yunzhao</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fu%2C+Ziwei%22">Fu, Ziwei</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cai%2C+Dachuan%22">Cai, Dachuan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Luo%2C+Qiang%22">Luo, Qiang</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> qiangluo@hospital.cqmu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Bose%2C+Anupama%22">Bose, Anupama</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> abose@wiley.com</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Food+Biochemistry%22">Journal of Food Biochemistry</searchLink>. 5/30/2026, Vol. 2026, p1-15. 15p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22PI3K%2FAKT%2FmTOR+pathway%22">PI3K/AKT/mTOR pathway</searchLink><br /><searchLink fieldCode="DE" term="%22Autophagy%22">Autophagy</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondria%22">Mitochondria</searchLink><br /><searchLink fieldCode="DE" term="%22Oxidative+stress%22">Oxidative stress</searchLink><br /><searchLink fieldCode="DE" term="%22Pomegranate%22">Pomegranate</searchLink><br /><searchLink fieldCode="DE" term="%22Apoptosis%22">Apoptosis</searchLink><br /><searchLink fieldCode="DE" term="%22Liver+injuries%22">Liver injuries</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Punicalagin, a major ellagitannin enriched in pomegranate (Punica granatum L.) peel, has been implicated in cellular redox regulation, yet its integrated mechanism against oxidative hepatocellular injury remains insufficiently defined. Here, we combined network pharmacology, molecular docking, and in vitro validation to elucidate the protective actions of punicalagin against hydrogen peroxide (H2O2)–induced injury in HepG2 cells. Punicalagin pretreatment markedly improved cell viability and suppressed intracellular reactive oxygen species accumulation following oxidative challenge. This protection was associated with improved mitochondrial function. Flow cytometry further demonstrated that punicalagin attenuated H2O2‐triggered apoptosis, consistent with modulation of the mitochondrial apoptotic cascade as evidenced by an increased Bcl‐2/Bax balance and reduced caspase‐3 activation. Punicalagin also enhanced autophagy, as indicated by increased LC3B‐II and decreased p62. Network pharmacology identified overlapping targets between punicalagin and liver injury, with enrichment analyses highlighting PI3K/AKT‐related signaling; docking predicted favorable binding of punicalagin to AKT1. Mechanistically, punicalagin blunted oxidative stress–induced phosphorylation of PI3K, AKT, and mTOR without altering total protein abundance. Importantly, pharmacological reactivation of AKT using SC79 mitigated punicalagin‐induced autophagy, supporting a pathway‐dependent mode of action. Collectively, these findings indicate that punicalagin alleviates oxidative hepatocellular injury, supporting its potential as a food‐derived bioactive for oxidative stress–related liver dysfunction. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Food Biochemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1155/jfbc/1703966 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 15 StartPage: 1 Subjects: – SubjectFull: PI3K/AKT/mTOR pathway Type: general – SubjectFull: Autophagy Type: general – SubjectFull: Mitochondria Type: general – SubjectFull: Oxidative stress Type: general – SubjectFull: Pomegranate Type: general – SubjectFull: Apoptosis Type: general – SubjectFull: Liver injuries Type: general Titles: – TitleFull: Mechanistic Insights Into the Hepatoprotective Effects of Punicalagin Against Oxidative Stress: Involvement of the PI3K/AKT/mTOR Pathway and Autophagy. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Yang, Xia – PersonEntity: Name: NameFull: Xiong, Chuan – PersonEntity: Name: NameFull: Zhang, Jing – PersonEntity: Name: NameFull: Chen, Qinqin – PersonEntity: Name: NameFull: Tang, Yunzhao – PersonEntity: Name: NameFull: Fu, Ziwei – PersonEntity: Name: NameFull: Cai, Dachuan – PersonEntity: Name: NameFull: Luo, Qiang – PersonEntity: Name: NameFull: Bose, Anupama IsPartOfRelationships: – BibEntity: Dates: – D: 30 M: 05 Text: 5/30/2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 01458884 Numbering: – Type: volume Value: 2026 Titles: – TitleFull: Journal of Food Biochemistry Type: main |
| ResultId | 1 |
