Related Experiment Video
Updated: Dec 15, 2025
Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy
Published on: May 26, 2023
The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway
Yoshiko Hada1, Haruhito A Uchida2, Nozomu Otaka1,3
1Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama 700-8558, Japan.
Abstract:
The world faces the serious problem of aging. In this study, we aimed to investigate the effect of chlorogenic acid (CGA) on vascular senescence. C57/BL6 female mice that were 14 ± 3 months old were infused with either Angiotensin II (AngII) or saline subcutaneously for two weeks. These mice were administered CGA of 20 or 40 mg/kg/day, or saline via oral gavage. AngII infusion developed vascular senescence, which was confirmed by senescence associated-β-galactosidase (SA-β-gal) staining. CGA administration attenuated vascular senescence in a dose-dependent manner, in association with the increase of Sirtuin 1 (Sirt1) and endothelial nitric oxide synthase (eNOS), and with the decrease of p-Akt, PAI-1, p53, and p21. In an in vitro study, with or without pre-treatment of CGA, Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with H2O2 for an hour, then cultured in the absence or presence of 0.5-5.0 μM CGA for the indicated time. Endothelial cell senescence was induced by H2O2, which was attenuated by CGA treatment. Pre-treatment of CGA increased Nrf2 in HUVECs. After H2O2 treatment, translocation of Nrf2 into the nucleus and the subsequent increase of Heme Oxygenase-1 (HO-1) were observed earlier in CGA-treated cells. Furthermore, the HO-1 inhibitor canceled the beneficial effect of CGA on vascular senescence in mice. In conclusion, CGA exerts a beneficial effect on vascular senescence, which is at least partly dependent on the Nuclear factor erythroid 2-factor 2 (Nrf2)/HO-1 pathway.
Insights
Chlorogenic acid (CGA) combats vascular senescence, a key aging problem. This study shows CGA protects blood vessels by activating the Nrf2/HO-1 pathway, offering a potential anti-aging strategy.
Area of Science:
- Gerontology
- Cardiovascular Biology
- Molecular Biology
Background:
- Aging is a global challenge with significant health implications.
- Vascular senescence, or the aging of blood vessels, contributes to age-related cardiovascular diseases.
- Identifying interventions to mitigate vascular aging is crucial.
Purpose of the Study:
- To investigate the potential of chlorogenic acid (CGA) in preventing and reversing vascular senescence.
- To elucidate the molecular mechanisms underlying CGA's effects on vascular aging.
Main Methods:
- In vivo study using aged C57/BL6 female mice infused with Angiotensin II (AngII) to induce vascular senescence.
- Administration of CGA at different doses (20 or 40 mg/kg/day) or saline via oral gavage.
- In vitro study using Human Umbilical Vein Endothelial Cells (HUVECs) exposed to hydrogen peroxide (H2O2) to induce senescence, with or without CGA pre-treatment.
- Analysis of senescence markers (SA-β-gal), key proteins (Sirt1, eNOS, p-Akt, PAI-1, p53, p21), and the Nrf2/HO-1 pathway.
Main Results:
- AngII infusion induced vascular senescence in mice, confirmed by SA-β-gal staining.
- CGA administration dose-dependently attenuated vascular senescence, increasing Sirt1 and eNOS while decreasing p-Akt, PAI-1, p53, and p21.
- In vitro, CGA treatment reduced H2O2-induced endothelial cell senescence.
- CGA pre-treatment enhanced Nrf2 activation and accelerated nuclear translocation, leading to increased Heme Oxygenase-1 (HO-1) expression in HUVECs.
- Inhibition of HO-1 abolished the beneficial effects of CGA on vascular senescence in mice.
Conclusions:
- Chlorogenic acid (CGA) demonstrates significant beneficial effects against vascular senescence.
- CGA's protective action is mediated, at least in part, through the activation of the Nuclear factor erythroid 2-factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway.
- CGA represents a promising therapeutic candidate for combating age-related vascular dysfunction.
Related Concept Videos
01:28Nitric Oxide Signaling Pathway
01:26Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
01:27Pharmacodynamics in Geriatric Patients: Effects of Age
01:19The Effect of Aging on Tissues