Hirudin ameliorates kidney injury in DKD mice by decreasing SOD2 β-hydroxybutyrylation mediated ROS level and NLRP3 inflammasome formation
Mechanism study published in FASEB Journal (2026)
Abstract
Inflammation and oxidative stress play crucial roles in the pathogenesis of diabetic kidney disease (DKD). Hirudin, a small molecular polypeptide derived from the salivary glands of leeches, is widely utilized in anti-coagulation and antithrombotic therapies. However, the effects and underlying molecular mechanisms of hirudin on DKD remain unclear. Db/db mice were employed to evaluate the effects of hirudin on DKD. Key parameters assessed included urinary albumin, oral glucose tolerance, glomerular diameter, and the expression levels of NLRP3, IL-1β, IL-18, caspase-1, and reactive oxygen species (ROS). Additionally, proteomic analysis was performed to measure the β-hydroxybutyrylation level of SOD2, and the effects of changes in SOD2 β-hydroxybutyrylation were evaluated by immunoprecipitation. In vivo experiments demonstrated that hirudin significantly improved urinary albumin levels, oral glucose tolerance, and glomerular diameter in diabetic mice. Furthermore, the β-hydroxybutyrylation level of SOD2 was reduced, leading to decreased production of ROS and suppression of NLRP3 inflammasome activation. In vitro experiments indicated that hirudin reduced the polarization of RAW264.7 cells, lowered their ROS levels, diminished NLRP3 inflammasome activation, and reduced the β-hydroxybutyrylation modification level of SOD2. Hirudin can alleviate the progression of DKD by reducing the β-hydroxybutyrylation level of SOD2, which in turn reduces ROS production and NLRP3 inflammasome activation, thereby suppressing inflammation. These findings provide new insights into the potential application of hirudin in the context of DKD.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Hirudin ameliorates diabetic kidney disease in mice by reducing SOD2 β-hydroxybutyrylation, lowering ROS, and inhibiting NLRP3 inflammasome — novel multi-pathway mechanism.
Why This Matters for Hirudotherapy
This study investigated the molecular mechanisms by which hirudin, a peptide derived from leech salivary glands, ameliorates diabetic kidney disease (DKD) using db/db mice and in vitro macrophage models. The findings revealed that hirudin reduces SOD2 β-hydroxybutyrylation, which subsequently lowers reactive oxygen species production and suppresses NLRP3 inflammasome activation, ultimately improving kidney parameters. For ASH, this expands the known therapeutic domain of leech-derived hirudin beyond anticoagulation into potentially novel anti-inflammatory and renoprotective applications. However, the research remains entirely preclinical, relying on animal and cell culture models, and offers no data on clinical human efficacy or direct hirudotherapy dosing.
Citation
Hirudin ameliorates kidney injury in DKD mice by decreasing SOD2 β-hydroxybutyrylation mediated ROS level and NLRP3 inflammasome formation.
Li Y et al. · FASEB journal, 2026
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