Albiflorin contributes to Xuebijing-mediated protection against sepsis-associated acute kidney injury by modulating the succinate-PFKFB3 immunometabolic axis

  • Int Immunopharmacol. 2026 Aug 1:182:116841. doi: 10.1016/j.intimp.2026.116841.
Yang Xu  1 ,  Jian Wei  1 ,  Mengting Chen  2 ,  Jingge Pang  2 ,  Wei Shi  1 ,  Siying Liu  1 ,  Tianfeng Hua  3 ,  Min Yang  4
Affiliations
  • 1. The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  • 2. School of Nursing, Anhui Medical University, Hefei, Anhui, China.
  • 3. The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address: [email protected].
  • 4. The Second Department of Intensive Care Unit, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; The Laboratory of Cardiopulmonary Resuscitation and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; School of Nursing, Anhui Medical University, Hefei, Anhui, China. Electronic address: [email protected].
PMID: 42134292 DOI: 10.1016/j.intimp.2026.116841
Abstract

Background: Xuebijing injection (XBJ) is widely used in China as an adjunctive therapy for sepsis and sepsis-associated acute kidney injury (SAKI). Here, we evaluated its immunometabolic and inflammatory effects in macrophages and identified candidate bioactive monomers to define the underlying mechanisms.

Methods: An inflammatory model was established in RAW264.7 macrophages using lipopolysaccharide, and targeted energy metabolomics identified succinate (SA) as a key responsive metabolite. XBJ-derived monomer screening prioritized Albiflorin for mechanistic investigation. Exogenous SA replenishment, pharmacological inhibition, and siRNA-mediated knockdown were used to investigate key glycolytic nodes and examine causal relationships. Key findings were validated in bone marrow-derived macrophages (BMDMs) and in a cecal ligation and puncture (CLP)-induced SAKI rat model.

Results: In RAW264.7 macrophages, XBJ markedly reduced SA, and phenotype-guided screening prioritized Albiflorin as a representative monomer for mechanistic investigation. Albiflorin improved mitochondrial respiration, attenuated oxidative stress, and restored Succinate Dehydrogenase activity, consistent with reduced SA accumulation. Exogenous SA replenishment partially reversed Albiflorin's anti-glycolytic and anti-inflammatory effects and restored PFKFB3 expression, whereas HIF-1α inhibition or knockdown did not block SA-induced PFKFB3 upregulation. PFKFB3 inhibition or knockdown reduced inflammatory outputs and lactate production and constrained SA-driven glycolytic enhancement. These findings were further supported in BMDMs and in a CLP-induced SAKI rat model.

Conclusion: This study identified SA as an XBJ-responsive metabolite linked to macrophage inflammation and prioritized Albiflorin as a representative effector monomer for mechanistic investigation. Albiflorin lowered SA burden and suppressed PFKFB3-associated glycolytic and inflammatory activation in macrophages, supporting its contribution to SAKI protection.

Keywords
Albiflorin; PFKFB3; Sepsis-associated acute kidney injury; Succinate; Xuebijing injection.
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