Pharmacological activation of SIRT1–AMPK by ginsenoside Rb1: a novel therapeutic strategy for pressure injury via dual suppression of ferroptosis and inflammation

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Background Pressure injuries (PIs) are a major clinical problem, and current treatments offer limited efficacy. Ferroptosis-driven oxidative damage and chronic inflammation severely impair wound healing. Ginsenoside Rb1 (Rb1), a bioactive component of Panax ginseng , possesses antioxidant and anti-inflammatory activities, yet its therapeutic potential in PI via ferroptosis regulation has not been investigated. This study aims to determine whether Rb1 promotes PI wound repair by activating the Sirtuin 1–AMP-activated protein kinase (SIRT1–AMPK) pathway to inhibit ferroptosis and inflammation, thereby providing a new pharmacological strategy for PI management. Method Transcriptomic profiling was performed on dorsal skin tissues from normal rats, pressure injury rats, and Rb1-treated rats using RNA sequencing to identify differentially expressed genes (DEGs), followed by Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, network pharmacology analysis, and protein–protein interaction (PPI) network construction to screen potential regulatory pathways. In vitro , ferroptosis was induced in an L929–HaCaT co-culture system using erastin/RSL3, and cells were treated with various concentrations of Rb1. Cell viability, reactive oxygen species (ROS) levels, ferroptosis-related markers (GPX4, SLC7A11, and ACSL4), and SIRT1–AMPK pathway proteins were evaluated by using the CCK-8, assay, fluorescence assays, Western blotting, and RT-qPCR. In vivo , a PI model was created in Sprague–Dawley (SD) rats, followed by administration of Rb1. Wound healing, histopathology, oxidative stress indices, inflammatory cytokines, and SIRT1–AMPK activation were assessed. Results Integrated transcriptomic and network pharmacology analyses identified the SIRT1–AMPK axis as a key mediator of Rb1-induced wound repair. In vitro , Rb1 dose-dependently attenuated erastin/RSL3-induced ferroptosis, decreased ROS levels, and increased the expressions of GPX4, SLC7A11, and ACSL4, while simultaneously activating SIRT1 and downstream p-AMPK. Rescue experiments showed that blocking the activities of SIRT1 or AMPK diminished the protective effects of Rb1 against ferroptosis. In vivo , high-dose Rb1 accelerated wound closure, activated SIRT1–AMPK signaling, enhanced ferroptosis-related protein expression, and reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels. Conclusion Rb1 functions as an SIRT1–AMPK activator that inhibits ferroptosis and inflammation to promote PI wound healing. These findings underpin the efficacy of Rb1 as a promising multi-target therapeutic candidate for future clinical development.

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