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International journal of molecular sciences2021; 22(10); 5333; doi: 10.3390/ijms22105333

Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium.

Abstract: Endometrosis is a reproductive pathology that is responsible for mare infertility. Our recent studies have focused on the involvement of neutrophil extracellular traps enzymes, such as elastase (ELA), in the development of equine endometrosis. Noscapine (NOSC) is an alkaloid derived from poppy opium with anticough, antistroke, anticancer, and antifibrotic properties. The present work investigates the putative inhibitory in vitro effect of NOSC on collagen type I alpha 2 chain () mRNA and COL1 protein relative abundance induced by ELA in endometrial explants of mares in the follicular or mid-luteal phases at 24 or 48 h of treatment. The mRNA was evaluated by qPCR and COL1 protein relative abundance by Western blot. In equine endometrial explants, ELA increased COL 1 expression, while NOSC inhibited it at both estrous cycle phases and treatment times. These findings contribute to the future development of new endometrosis treatment approaches. Noscapine could be a drug capable of preventing collagen synthesis in mare's endometrium and facilitate the therapeutic approach.
Publication Date: 2021-05-19 PubMed ID: 34069423PubMed Central: PMC8159119DOI: 10.3390/ijms22105333Google Scholar: Lookup
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  • Journal Article

Summary

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The research explores the potential role of noscapine, a poppy-derived alkaloid, in inhibiting the buildup of a type of collagen stimulated by elastase in horse endometrium, a condition linked to infertility. The findings suggest noscapine’s promise in offering novel treatment approaches for endometrosis.

Objective of the Study

  • The study aims to investigate the potential of noscapine (an alkaloid derived from poppy) to inhibit elastase-induced collagen deposition in horse endometrium.
  • The research further aims to provide insights into new ways of treating endometrosis, a condition associated with mare infertility.

Methods and Analysis

  • Noscapine’s inhibitory effect on collagen type I alpha 2 chain (a type of collagen protein) mRNA and COL1 protein relative abundance were investigated. These compounds are typically produced when elastase acts on the endometrium.
  • The investigations were conducted on endometrial explants (samples of endometrial tissue) of mares in two phases of their reproductive cycle – the follicular and mid-luteal phases.
  • Evaluation of mRNA was performed using qPCR (quantitative Polymerase Chain Reaction), a technique that allows scientists to see how much of a specific mRNA is present in a tissue sample.
  • The relative abundance of COL1 protein was measured with Western blotting, a method of identifying specific proteins in a mixture.

Findings and Implications

  • The findings showed that elastase increased the expression of COL1 (collagen protein) in horse endometrial samples, while noscapine inhibited this increase.
  • The inhibition happened in both phases of the estrous cycle and at both 24 and 48 hours of treatment.
  • This suggests that noscapine could be a potential drug for preventing collagen synthesis in the endometrium of mares – a major factor in the development of endometrosis, a condition that often leads to infertility in horses.
  • If further research supports these findings, noscapine could pave the way for new, effective treatments for endometrosis and potentially boost fertility in horses.

Cite This Article

APA
Amaral A, Fernandes C, Szóstek-Mioduchowska A, Rebordão MR, Skarzynski DJ, Ferreira-Dias G. (2021). Noscapine Acts as a Protease Inhibitor of In Vitro Elastase-Induced Collagen Deposition in Equine Endometrium. Int J Mol Sci, 22(10), 5333. https://doi.org/10.3390/ijms22105333

Publication

ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 22
Issue: 10
PII: 5333

Researcher Affiliations

Amaral, Ana
  • CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
Fernandes, Carina
  • CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
Szóstek-Mioduchowska, Anna
  • Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
Rebordão, Maria Rosa
  • CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.
  • Polytechnic of Coimbra, Coimbra Agriculture School, Bencanta, 3045-601 Coimbra, Portugal.
Skarzynski, Dariusz Jan
  • Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland.
Ferreira-Dias, Graça
  • CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Departamento de Morfologia e Função, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, Portugal.

MeSH Terms

  • Animals
  • Collagen / metabolism
  • Collagen Type I / drug effects
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Endometriosis / drug therapy
  • Endometriosis / metabolism
  • Endometriosis / veterinary
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Estrous Cycle
  • Extracellular Traps / metabolism
  • Female
  • Fibrosis
  • Horse Diseases / pathology
  • Horses
  • Noscapine / metabolism
  • Noscapine / pharmacology
  • Pancreatic Elastase / metabolism
  • Protease Inhibitors / pharmacology

Grant Funding

  • PPN/BIL/2018/1/00250/U/0001 / Narodowa Agencja Wymiany Akademickiej
  • UIDB/00276/2020 / Fundau00e7u00e3o para a Ciu00eancia e a Tecnologia
  • PTDC/CVT-REP/4202/2014 / Fundau00e7u00e3o para a Ciu00eancia e a Tecnologia
  • SFRH/BD/101058/2014 / Fundau00e7u00e3o para a Ciu00eancia e a Tecnologia

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 3 times.
  1. Amaral A, Cebola N, Szóstek-Mioduchowska A, Rebordão MR, Kordowitzki P, Skarzynski D, Ferreira-Dias G. Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium. Int J Mol Sci 2023 Feb 10;24(4).
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  2. Amaral A, Fernandes C, Szóstek-Mioduchowska A, Lukasik K, Rebordão MR, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G. The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium. Life (Basel) 2021 Oct 19;11(10).
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  3. Ferreira-Dias GM, Alpoim-Moreira J, Szóstek-Mioduchowska A, Rebordão MR, Skarzynski DJ. The path to fertility: Current approaches to mare endometritis and endometrosis. Anim Reprod 2024;21(3):e20240070.
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