Astragaloside II-preconditioned bone marrow mesenchymal stem cells attenuate sepsis-induced acute lung injury by restoring mitochondrial function via NRF2/PGC-1α pathway activation

  • Biochem Biophys Res Commun. 2026 Sep 3:829:154148. doi: 10.1016/j.bbrc.2026.154148.
Hongyu Zhang  1 ,  Yan Sun  2 ,  Yongjun Tang  2 ,  Lidan Yao  2 ,  Xiherezhati Abulimiti  2 ,  Qinfen Wu  3
Affiliations
  • 1. Department of Critical Care Medicine, The Second Affiliated Hospital of Xinjiang Medical University, Wulumuqi, Xinjiang, 830000, China. Electronic address: [email protected].
  • 2. Department of Critical Care Medicine, The Second Affiliated Hospital of Xinjiang Medical University, Wulumuqi, Xinjiang, 830000, China.
  • 3. Department of Neurology, The Second Affiliated Hospital of Xinjiang Medical University, Wulumuqi, Xinjiang, 830000, China. Electronic address: [email protected].
PMID: 42349124 DOI: 10.1016/j.bbrc.2026.154148
Abstract

Objective: Sepsis-induced acute lung injury (ALI) is characterized by mitochondrial dysfunction and oxidative stress, contributing to high mortality rates. This study investigates the protective effects of astragaloside II (ASII)-preconditioned bone marrow mesenchymal stem cells (BMSCs) on sepsis-induced ALI and explores the underlying mechanism.

Methods: BMSCs were isolated from C57BL/6 mice and preconditioned with ASII. The viability, migration, and Apoptosis of these BMSCs were assessed. LPS-injured MLE-12 cells were co-cultured with ASII-preconditioned BMSCs to evaluate their protective effects on cell survival, Apoptosis, mitochondrial membrane potential, and oxidative stress markers. A cecal ligation and puncture (CLP)-induced sepsis model in mice was used to assess the in vivo efficacy of ASII-preconditioned BMSCs on lung injury, pulmonary edema, inflammation, and Apoptosis. The involvement of the NRF2 pathway was confirmed using a specific inhibitor, ML385.

Results: BMSCs pretreated with ASII exhibited enhanced viability, migration, and resistance to Apoptosis. In LPS-injured MLE-12 cells, ASII-preconditioned BMSCs improved cell survival, reduced Apoptosis, and restored mitochondrial membrane potential by modulating mitochondrial dynamics (increasing Mfn2 and decreasing Fis1 expression) and promoting mitochondrial biogenesis via the NRF2/PGC-1α/Nrf1/Tfam signaling axis. These protective effects were attenuated upon NRF2 inhibition with ML385, confirming NRF2 pathway involvement. In a CLP-induced sepsis model, ASII-preconditioned BMSCs significantly reduced lung injury, pulmonary edema, and Apoptosis, while lowering inflammatory cytokine levels (TNF-α, IL-1β, IL-6) and increasing TIPE2 in bronchoalveolar lavage fluid.

Conclusions: Collectively, these findings highlight ASII preconditioning as an effective strategy to enhance BMSCs therapeutic efficacy for sepsis-induced ALI through NRF2-mediated mitochondrial protection.

Keywords
Acute lung injury; Astragaloside II; Bone marrow mesenchymal stem cells; Mitochondrial function; NRF2 pathway; Sepsis.
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