Evaluation of Naturally Occurring HIF-1 Inhibitors for Pulmonary Arterial Hypertension

Midori A. Arai, Kota Sakuraba, Yoshinori Makita, Yasumasa Hara, Masami Ishibashi

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Pulmonary arterial hypertension (PAH) is a rare and severe progressive disorder characterized by high pulmonary artery pressure. Chronic hypoxia causes a metabolic disorder and the Warburg effect in pulmonary arterial smooth muscle cells (PASMCs). Pyruvate dehydrogenase kinase 1 (PDK1) is a key enzyme in Warburg effect increased by hypoxia-inducible factor (HIF-1). We constructed a cell-based luciferase assay system for HIF-1 inhibitors. Using this system, six HIF-1 inhibitors were identified. Among these inhibitors, the effect of tagitinin C (1) on PASMC was investigated. Tagitinin C (1) clearly decreased the amount of HIF-1β and the HIF-1 target PDK1. This result indicates that HIF-1 inhibitors effectively decrease PDK1 activity, which is a cause of the metabolic disorder and Warburg effect observed in PASMCs. Identifying naturally occurring HIF-1 inhibitors could provide novel insights into the development of PAH medications.

Original languageEnglish
Pages (from-to)2799-2804
Number of pages6
Issue number18
Publication statusPublished - 2021 Sept 14


  • HIF-1
  • hypoxia
  • inhibitor
  • natural products
  • pulmonary arterial hypertension

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry


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