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Indigo Leaves-Induced Pulmonary Arterial Remodeling without Right Ventricular Hypertrophy in Rats.

Honoka Tsunematsu1, Masaki Imanishi1, Yuka Uemura1

  • 1Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences.

Biological & Pharmaceutical Bulletin
|July 31, 2024
PubMed
Summary

Indigo naturalis, used for ulcerative colitis, can cause pulmonary arterial hypertension. Its component indican and metabolite IS induce endothelin-1, leading to lung artery remodeling in a rat model.

Keywords:
endothelin-1indicanindigo leafindigo naturalisindoxyl sulfatepulmonary arterial hypertension

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Area of Science:

  • Pharmacology
  • Toxicology
  • Cardiovascular Medicine

Background:

  • Indigo naturalis (IN) is a traditional Chinese medicine with anti-inflammatory uses.
  • Long-term IN use is linked to pulmonary arterial hypertension (PAH) in ulcerative colitis (UC) patients.

Purpose of the Study:

  • To investigate the mechanisms by which IN induces PAH.
  • To identify the role of indigo leaves (IL) and their components in PAH development.

Main Methods:

  • A rat model was used to study the effects of long-term, high-dose IL administration.
  • Gene Expression Omnibus analysis was performed to identify key regulators of PAH.
  • Endothelin-1 (ET-1) expression in lung endothelial cells (ECs) was analyzed.

Main Results:

  • Long-term IL administration induced pulmonary artery medial thickening in rats.
  • IL administration increased ET-1 expression in lung ECs.
  • The IL components indican and IS were found to induce ET-1 mRNA expression via a reactive oxygen species-dependent pathway, linked to pulmonary arterial remodeling.

Conclusions:

  • Indican and its metabolite IS in indigo leaves play a role in inducing ET-1 expression.
  • This ET-1 induction contributes to pulmonary arterial remodeling and PAH development.
  • Findings elucidate the mechanism of IN-induced PAH.