Therapeutic effect of Garcinia cambogia extract and hydroxycitric acid inhibiting hypoxia-inducible factor in a murine model of age-related macular degeneration

Mari Ibuki, Chiho Shoda, Yukihiro Miwa, Ayako Ishida, Kazuo Tsubota, Toshihide Kurihara

Research output: Contribution to journalArticle

Abstract

Background: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. Methods: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. Results: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.

Original languageEnglish
Article number5049
JournalInternational journal of molecular sciences
Volume20
Issue number20
DOIs
Publication statusPublished - 2019 Oct 2

Fingerprint

Garcinia cambogia
Garcinia
degeneration
hypoxia
Macular Degeneration
Therapeutic Uses
acids
Acids
Vascular Endothelial Growth Factor A
Assays
Choroidal Neovascularization
Animals
angiogenesis
Luciferases
Laser beam effects
Transcription
animal models
Pigments
Retinal Pigments
food

Keywords

  • Age-related macular degeneration
  • Choroid
  • Garcinia cambogia
  • Hydroxycitric acid
  • Hypoxia-inducible factor
  • Laser induced neovascularization
  • Retina

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Therapeutic effect of Garcinia cambogia extract and hydroxycitric acid inhibiting hypoxia-inducible factor in a murine model of age-related macular degeneration. / Ibuki, Mari; Shoda, Chiho; Miwa, Yukihiro; Ishida, Ayako; Tsubota, Kazuo; Kurihara, Toshihide.

In: International journal of molecular sciences, Vol. 20, No. 20, 5049, 02.10.2019.

Research output: Contribution to journalArticle

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