Hirudin ameliorates kidney injury in DKD mice by decreasing SOD2 β-hydroxybutyrylation mediated ROS level and NLRP3 inflammasome formation

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.

Hirudin ameliorates diabetic kidney disease in mice by reducing SOD2 β-hydroxybutyrylation, lowering ROS, and inhibiting NLRP3 inflammasome — novel multi-pathway mechanism.

Leech-derived molecules this paper discusses, each with a full profile in the ASH compound registry:

Explore cómo esta investigación se conecta con la práctica clínica

More peer-reviewed studies in Farmacología salival.

• Novel Leech Antimicrobial Peptides — Hirunipins — Kumar et al. (2025)
• 434 Salivary Proteins — Integrated Proteomics of Hirudo medicinalis — Liu et al. (2019)
• Medicinal Leech Genome Assembly — Anticoagulant Gene Catalog — Kvist et al. (2020)
• Effects of hirudotherapy on liver functions, lipid profile, and insulin sensitivity in rats with metabolic syndrome — Bilden A et al. (2026)
• Efficacy and Safety of Hirudotherapy for Improving Sperm Quality Parameters in Male Infertility: A Randomized Controlled Trial — Abtahi-Forooshani M et al. (2026)
• [Medicinal leeches and hirudotherapy] — Gödekmerdan A et al. (2011)
• PEROXIDATION OF SALIVA LIPIDS IN PATIENTS WITH POSTCOVID SYNDROME DURING HIRUDOTHERAPY — Serikbayeva S et al. (2024)
• Medicinal leech therapy in pain syndromes: a narrative review — Koeppen D, Aurich M, Rampp T (2014)
• Leech therapy in the treatment of a penile haematoma in a stallion — Nowicki A, Jaworska J, Baranski W (2021)
• Leech therapy (Hirudo medicinalis) attenuates testicular damages induced by testicular ischemia/reperfusion in an animal model — Davoodi F et al. (2021)

Browse all ASH-analysed research →