Study of olive leaf extract on skin aging: Ex vivo, animal, and randomized double-blind placebo-controlled clinical studies

Authors

  • Marie Hayashida
  • Hiromasa Suzuki
  • Rie Kitade
  • Miki Yokozawa
  • Hiroko Isoda
  • Masahito Ishikawa

DOI:

https://doi.org/10.31989/ffhd.v16i6.1975

Abstract

Background: Water extract of olive leaf (WOL) inhibits excess reactive oxygen species (ROS) production caused by ultraviolet (UV) irradiation, improves fibroblast survival rate, and inhibits melanin synthesis. However, no studies have examined its effects on skin stem cells.

Objectives: This study aimed to investigate whether WOL affects the expression of epidermal and dermal stem cell markers, including HIF-1α, in human-derived cells and senescence-accelerated mice as well as skin aging in healthy participants.

Methods: WOL (final concentration 25 or 120 μg/mL) was added to living human skin explants, and HIF-1α, HES1, Filaggrin, and Claudin 1 expression levels were evaluated by fluorescent immunostaining on day 9 or 10 of culture. Senescence-accelerated mouse-prone 8 (SAMP8) mice were administered WOL at 103 mg/kg body weight for 30 days, and CD271, NG2, and CK15 expression in the skin were evaluated using fluorescent immunostaining. In a clinical trial, 50 healthy Japanese individuals (aged 40–69 years) were divided into a WOL intake group (WOL 250 mg/day) and a placebo group, and skin age and moisture were evaluated after 12 weeks.

Results: The ex vivo and in vivo studies showed that WOL treatment increased markers associated with epidermal and dermal stem cell activity and differentiation. In the clinical trial, skin age was lower in the WOL group, although the difference did not reach statistical significance in the overall cohort. Exploratory subgroup analysis showed a significant decrease in skin age among participants without regular exercise habits.

Conclusion: WOL may influence markers associated with epidermal and dermal stem cell activity and may support improvement in skin aging outcomes, particularly in healthy individuals who do not exercise regularly.

Novelty: This is the first study to demonstrate that WOL increases the expression of markers associated with epidermal and dermal stem cells and shows potential for improving skin age, particularly in individuals without regular exercise habits.

Keywords: Olive leaf extract; Skin stem cells; HIF-1α; Skin age; Functional food science; Clinical trial

Published

2026-06-05

Issue

Section

Research Articles