Identification of Marrubiin as a Cathepsin C Inhibitor for Treating Rheumatoid Arthritis
Fei-Long Zhou1,2, Yu Zhang2, Cui Chang2
1Medical School, Fuyang Normal University, Fuyang 236037, China.
Molecules (Basel, Switzerland)
|November 13, 2025
Summary
Marrubiin, a natural compound, effectively inhibits Cathepsin C (CTSC), a key enzyme in inflammatory diseases. This potent CTSC inhibitor shows promise for treating neutrophil-related inflammatory conditions.
Area of Science:
- Biochemistry
- Pharmacology
- Immunology
Background:
- Cathepsin C (CTSC) is crucial for neutrophil serine protease (NSP) maturation and inflammatory processes.
- CTSC is a significant therapeutic target for inflammatory diseases.
Purpose of the Study:
- To identify natural product inhibitors of CTSC.
- To evaluate the therapeutic potential of marrubiin in inflammatory disease models.
Main Methods:
- Large-scale screening of a natural product library.
- In vitro assays measuring CTSC and NSP activity, cytotoxicity, nitric oxide release, and cytokine/chemokine levels.
- Molecular docking to predict binding interactions.
- In vivo studies in mouse models of inflammation and arthritis.
Main Results:
- Marrubiin identified as a potent CTSC inhibitor (nM range) with low cytotoxicity.
- Marrubiin reduced NSP activity, nitric oxide production, and modulated cytokine/chemokine levels in vitro.
- In vivo studies demonstrated marrubiin's efficacy in reducing CTSC and NSP activity in blood and bone marrow, comparable to AZD7986.
- Marrubiin showed therapeutic effects in an adjuvant-induced arthritis model.
Conclusions:
- Marrubiin is a promising natural product inhibitor of CTSC.
- Marrubiin demonstrates therapeutic potential for neutrophil-related inflammatory diseases.
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