Anti-Hyperuricemic and Nephroprotective Effects of Hydrolysate Derived from Silkworm Pupae (Bombyx mori): In Vitro and In Vivo Study

Nutrients. 2025 May 6;17(9):1596. doi: 10.3390/nu17091596.

Abstract

Background: Hyperuricemia is a prevalent metabolic disorder characterized by elevated serum uric acid (UA) levels.

Methods: In this study, hydrolysate (SPP) derived from silkworm pupae protein was isolated and identified, demonstrating anti-hyperuricemic activity. The research aimed to investigate its anti-hyperuricemic and nephroprotective effects, along with potential mechanisms, through in vitro assays and in vivo experiments using potassium oxonate/hypoxanthine-induced hyperuricemic mice.

Results: The SPP exhibited significant xanthine oxidase (XOD) inhibitory activity, with an IC50 value of 7.41 mg/mL. Furthermore, SPP administration effectively reduced serum UA, blood urea nitrogen (BUN), creatinine levels, and renal pro-inflammatory cytokines in hyperuricemic mice. Mechanistic studies revealed that the anti-hyperuricemic effects of SPP may involve XOD inhibition and the modulation of renal UA transporters, specifically upregulating organic anion transporter 1 (OAT1) and ATP-binding cassette subfamily G member 2 (ABCG2) expression. Histopathological analysis and inflammatory cytokine profiling further demonstrated that SPP alleviated renal inflammation and pathological damage.

Conclusions: These findings suggest that SPP possesses a notable urate-lowering efficacy and renal protective properties, highlighting its potential as a therapeutic agent for the management and prevention of hyperuricemia (HUA).

Keywords: anti-hyperuricemic; anti-inflammatory; peptides; silkworm pupae; xanthine oxidase.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Animals
  • Blood Urea Nitrogen
  • Bombyx* / chemistry
  • Creatinine / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Hyperuricemia* / blood
  • Hyperuricemia* / chemically induced
  • Hyperuricemia* / drug therapy
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Mice
  • Organic Anion Transport Protein 1 / metabolism
  • Oxonic Acid
  • Protein Hydrolysates* / pharmacology
  • Uric Acid / blood
  • Xanthine Oxidase / antagonists & inhibitors
  • Xanthine Oxidase / metabolism

Substances

  • Uric Acid
  • Xanthine Oxidase
  • Protein Hydrolysates
  • Organic Anion Transport Protein 1
  • Cytokines
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Creatinine
  • Oxonic Acid
  • potassium oxonate