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Olive mill wastewater and hydroxytyrosol inhibits atherogenesis in apolipoprotein E-deficient mice

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Abstract

The Mediterranean diet, which is characterized by high consumption of olive oil, prevents cardiovascular disease. Meanwhile, olive mill wastewater (OMWW), which is obtained as a byproduct during olive oil production, contains various promising bioactive components such as water-soluble polyphenols. Hydroxytyrosol (HT), the major polyphenol in OMWW, has anti-oxidative and anti-inflammatory properties; however, the atheroprotective effects of OMWW and HT remain to be fully understood. Here, we investigated the effect of OMWW and HT on atherogenesis. Male 8-week-old apolipoprotein E-deficient mice were fed a western-type diet supplemented with OMWW (0.30%w/w) or HT (0.02%w/w) for 20 weeks. The control group was fed a non-supplemented diet. OMWW and HT attenuated the development of atherosclerosis in the aortic arch as determined by Sudan IV staining (P < 0.01, respectively) without alteration of body weight, plasma lipid levels, and blood pressure. OMWW and HT also decreased the production of oxidative stress (P < 0.01, respectively) and the expression of NADPH oxidase subunits (e.g., NOX2 and p22phox) and inflammatory molecules (e.g. IL-1β and MCP-1) in the aorta. The results of in vitro experiments demonstrated that HT inhibited the expression of these molecules that were stimulated with LPS in RAW264.7 cells, murine macrophage-like cells. OMWW and HT similarly attenuated atherogenesis. HT is a major component of water-soluble polyphenols in OMWW, and it inhibited inflammatory activation of macrophages. Therefore, our results suggest that the atheroprotective effects of OMWW are at least partially attributable to the anti-inflammatory effects of HT.

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Abbreviations

ApoE− / − :

Apolipoprotein E-deficient

Ctrl:

Control

EVOO:

Extra-virgin olive oil

HT:

Hydroxytyrosol

ICAM-1:

Intercellular adhesion molecule-1

IL:

Interleukin

MCP-1:

Monocyte chemoattractant protein-1

OMWW:

olive mill wastewater

PAI-1:

Plasminogen activator inhibitor-1

qPCR:

Quantitative real-time PCR

VCAM-1:

Vascular cell adhesion molecule-1

WTD:

Western-type diet

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Acknowledgements

The authors thank Shintaro Okamoto and Etsuko Uematsu for their technical assistance.\

Funding

This work was partially supported by JSPS Kakenhi Grants (Number 19K08584 to D.F. and Number 19H03654 to M.S.), Bristol-Myers Squibb Research Grants (D.F.), The Uehara Memorial Foundation (D.F.), Takeda Science Foundation (M.S.), and the Vehicle Racing Commemorative Foundation (M.S.). The funders had no role in the study design, data collection and analysis, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan

    Tomoya Hara, Daiju Fukuda, Byambasuren Ganbaatar, Phuong Tran Pham, Kunduziayi Aini, Arief Rahadian, Kumiko Suto, Shusuke Yagi, Kenya Kusunose & Masataka Sata

  2. Department of Cardio-Diabetes Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, 770-8503, Japan

    Daiju Fukuda

  3. Department of Community Medicine for Cardiology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, 770-8503, Japan

    Hirotsugu Yamada

  4. Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, Tokushima, 770-8503, Japan

    Takeshi Soeki

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  1. Tomoya Hara
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The Department of Cardio-Diabetes Medicine, Tokushima University Graduate School is supported in part by unrestricted research grants from Boehringer Ingelheim. The authors declare that they have no conflict of interest.

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Hara, T., Fukuda, D., Ganbaatar, B. et al. Olive mill wastewater and hydroxytyrosol inhibits atherogenesis in apolipoprotein E-deficient mice. Heart Vessels 38, 1386–1394 (2023). https://doi.org/10.1007/s00380-023-02290-5

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