Antler base (Cervus nippon Temminck) peptides modulate the NLRP3 inflammatory pyroptosis and Nrf2/HO-1/NQO1 signaling pathways to ameliorate osteoarthritis: a structural and mechanistic study

  • 0Key laboratory of Microecology-Immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang Province 154000, China.

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Summary

This summary is machine-generated.

Cervus nippon Temminck antler base peptides (CNCPs) show potential in treating osteoarthritis by reducing inflammation and oxidative stress. These peptides regulate key signaling pathways, offering a novel therapeutic approach for osteoarthritis.

Area Of Science

  • Biochemistry
  • Pharmacology
  • Molecular Biology

Background

  • Antler base (Cervus nippon Temminck) is a traditional Chinese medicine used for osteoarthritis (OA).
  • The molecular mechanisms and active compounds responsible for its therapeutic effects on OA remain largely unknown.

Purpose Of The Study

  • To elucidate the mechanism of action and identify the active components of Cervus nippon Temminck antler base peptides (CNCPs) in ameliorating OA.
  • To investigate the structural characteristics of bioactive CNCPs.

Main Methods

  • Characterization of CNCPs using FTIR and HPLC.
  • Evaluation of CNCPs' protective effects and mechanisms in a papain-induced OA rat model via histopathology, ELISA, Western blotting, qRT-PCR, and immunofluorescence.
  • Isolation and purification of CNCPs using Sephadex G-15, bioactivity screening in an IL-1β-induced in vitro model, and identification of active components by LC-MS/MS.

Main Results

  • CNCPs significantly reduced cartilage erosion, preserved cartilage integrity, modulated OA-related protein expression, and normalized serum levels of pro-inflammatory and oxidative stress markers in OA rats.
  • CNCPs inhibited NLRP3 inflammasome-mediated pyroptosis and activated the Nrf2 pathway.
  • The most active fraction, CNCPs-III (<1.5 kDa), was rich in hydrophobic amino acids like AGPAGA, VGPV, and LLGDV.

Conclusions

  • CNCPs effectively mitigate OA-induced inflammation and oxidative stress.
  • The therapeutic effects are mediated through the regulation of the NLRP3 inflammatory pyroptosis and Nrf2/HO-1/NQO1 signaling pathways.
  • CNCPs demonstrate potential in delaying osteoarthritis progression.