TY  - EJOU
AU  - Su, Wentao 
AU  - Gulijiakela, Aishan 
AU  - Xiong, Jihao 
AU  - Zhang, San 
AU  - Ma, Ke 

TI  - Salviadione Attenuates Acute Lung Injury by Targeting VDAC1-Mediated Mitochondrial Ferroptosis
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - <b>Objective:</b> Mitochondrial dysfunction and ferroptosis contribute critically to acute lung injury (ALI), yet therapies targeting this pathway remain limited. This study investigates whether Salviadione, a rare alkaloid, protects against lipopolysaccharide (LPS)-induced epithelial damage by modulating the mitochondrial ferroptosis pathway. <b>Methods:</b> Network pharmacology, molecular docking, and molecular dynamics simulations identified potential targets. An <i>in vitro</i> model of lung epithelial injury was established using BEAS-2B cells exposed to LPS. Cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, Fe<sup>2+</sup> accumulation, glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) expression, mitochondrial membrane potential (ΔΨm), mitochondrial reactive oxygen species (ROS), and ATP content were measured. voltage-dependent anion channel 1 (VDAC1) silencing and ferroptosis modulators (RSL3, ferrostatin-1) were used for mechanistic validation. <b>Results:</b> Salviadione (10 μM) increased LPS-reduced cell viability from 48.2 ± 3.1% to 82.5 ± 2.7% (<i>p</i> &lt; 0.05) and decreased LDH release by 41.3% (<i>p</i> &lt; 0.05). It reduced lipid peroxidation (by 58.6%, <i>p</i> &lt; 0.05) and Fe<sup>2+</sup> accumulation (by 47.2%, <i>p</i> &lt; 0.05), restored GPX4 expression (to 86.4 ± 4.2% of control), and normalized ACSL4. Mitochondrial ΔΨm improved by 2.1-fold (<i>p</i> &lt; 0.01), mitochondrial ROS decreased by 53.4% (<i>p</i> &lt; 0.05), and ATP content increased by 2.3-fold (<i>p</i> &lt; 0.05) versus LPS alone. VDAC1 knockdown abolished Salviadione’s protective effects, while RSL3 reversed and ferrostatin-1 enhanced its actions. <b>Conclusion:</b> Salviadione protects lung epithelial cells from LPS-induced injury by stabilizing VDAC1, preserving mitochondrial function, and inhibiting ferroptosis via the VDAC1/GPX4 axis. These findings establish a foundation for Salviadione-based therapies targeting mitochondrial ferroptosis in ALI.
KW  - Salviadione; acute lung injury; ferroptosis; BEAS-2B cells; mitochondrial dysfunction; voltage-dependent anion channel 1 (VDAC1); glutathione peroxidase 4 (GPX4)

DO  - 10.32604/biocell.2026.081235