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] |
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| Database: | Engineering Source |
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| 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] |
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| ISSN: | 01458884 |
| DOI: | 10.1155/jfbc/1703966 |
