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Procyanidin B2 Ameliorates Acute Alcoholic Liver Injury by Suppressing the PI3K-Akt/NF-κB Signaling Pathway to
Jianjin Guo1, Zhaohuan Li2, Jing Gao3
1State Key Laboratory of Natural Product Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Abstract:
Acute alcoholic liver injury is a significant clinical challenge with complex pathogenesis. This study systematically investigated the hepatoprotective effect of procyanidin B2 (PB2) using an integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and in vivo/in vitro validation. Network analysis identified 161 common targets and highlighted the PI3K-Akt/NF-κB pathway as central. PB2 demonstrated high binding affinity to core targets such as SRC. In a mouse model, PB2 intervention significantly attenuated histopathological damage, reduced oxidative stress markers, improved lipid profiles, and suppressed pro-inflammatory cytokines while enhancing IL-10 expression. Western blot analysis confirmed PB2 dose-dependently inhibited phosphorylation of key proteins in the PI3K-Akt and NF-κB pathways. Cellular experiments further validated that PB2 alleviated ethanol-induced injury, apoptosis, and inflammatory response. These findings reveal that PB2 exerts protective effects against acute alcoholic liver injury primarily by modulating the PI3K-Akt/NF-κB signaling axis, offering a promising natural therapeutic candidate.
Insights
Procyanidin B2 (PB2) shows promise in treating alcoholic liver injury. This natural compound protects liver cells by targeting key inflammatory and survival pathways, offering a potential new therapy.
Area of Science:
- Hepatology
- Pharmacology
- Biochemistry
Background:
- Acute alcoholic liver injury (AALI) presents a significant clinical challenge.
- Its pathogenesis is complex and multifactorial.
- Effective therapeutic strategies for AALI are limited.
Purpose of the Study:
- To investigate the hepatoprotective effects of procyanidin B2 (PB2) against AALI.
- To elucidate the underlying molecular mechanisms of PB2's action.
- To validate PB2's therapeutic potential through integrated computational and experimental approaches.
Main Methods:
- Network pharmacology identified key targets and pathways.
- Molecular docking and dynamics simulations assessed binding affinities.
- In vivo (mouse model) and in vitro (cellular) experiments validated efficacy.
- Western blot analysis confirmed pathway modulation.
Main Results:
- Network analysis highlighted the PI3K-Akt/NF-κB pathway as central to AALI.
- PB2 exhibited strong binding affinity to core targets like SRC.
- PB2 treatment attenuated liver damage, oxidative stress, and inflammation in vivo.
- PB2 alleviated ethanol-induced injury, apoptosis, and inflammation in vitro.
- PB2 dose-dependently inhibited key signaling pathway phosphorylation.
Conclusions:
- Procyanidin B2 (PB2) demonstrates significant hepatoprotective effects against acute alcoholic liver injury.
- PB2 primarily acts by modulating the PI3K-Akt/NF-κB signaling axis.
- PB2 is a promising natural therapeutic candidate for AALI.
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