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Updated: Feb 10, 2026

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Published on: June 10, 2021
Hydroxytyrosol and olive leaf extract exert cardioprotective effects by inhibiting GRP78 and CHOP expression
Li-Xing Wu1, Yu-Yu Xu1, Zhi-Jian Yang2
1Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Abstract:
Myocardial infarction triggers massive biochemical changes, even cardiac cell death. Endoplasmic reticulum stress is involved in the pathology of myocardial infarction-mediated apoptosis. In the present study, myocardial cell line H9c2 cells were treated with cobalt chloride (CoCl2) to induce hypoxia. Isoproterenol was used for two successive days to induce myocardial infarction in SD rats. The cardioprotective effect of olive leaf extract (OLE) and its main constituent hydroxytyrosol and the underlying mechanisms were evaluated. The results showed that hydroxytyrosol markedly protected H9c2 cells against CoCl2-induced apoptosis. Hydroxytyrosol could reduce the mRNA and protein expression of GRP78 and CHOP induced by CoCl2 in vitro. In vivo, the decreased ejection fraction and fractional shortening, increased heart weight/body ratio, the formation of infarction, disordered cardiac muscle fibers and infiltration of inflammatory cells induced by isoproterenol could be significantly ameliorated by pretreatment with OLE for a month. Similarly, OLE could also reverse the increase of GRP78 and CHOP expression induced by isoproterenol. Therefore, OLE and hydroxytyrosol exert a cardioprotective effect through endoplasmic reticulum stress, which could be a new target for the prevention and treatment of cardiovascular diseases.
Insights
Olive leaf extract (OLE) and hydroxytyrosol protect against heart damage by reducing endoplasmic reticulum stress. This finding offers a new therapeutic target for cardiovascular diseases.
Area of Science:
- Cardiovascular Research
- Cellular Biology
- Pharmacology
Background:
- Myocardial infarction (MI) causes significant cell death and biochemical alterations.
- Endoplasmic reticulum (ER) stress is implicated in MI-induced apoptosis.
- Identifying novel therapeutic targets for cardiovascular diseases is crucial.
Purpose of the Study:
- To evaluate the cardioprotective effects of olive leaf extract (OLE) and hydroxytyrosol.
- To investigate the underlying mechanisms involving endoplasmic reticulum stress.
- To explore potential new treatments for myocardial infarction.
Main Methods:
- In vitro: H9c2 cells treated with cobalt chloride (CoCl2) to induce hypoxia and ER stress.
- In vivo: Myocardial infarction induced in SD rats using isoproterenol; rats pretreated with OLE.
- Assessed cell viability, apoptosis markers (GRP78, CHOP), cardiac function (ejection fraction, fractional shortening), and cardiac histology.
Main Results:
- Hydroxytyrosol protected H9c2 cells from CoCl2-induced apoptosis, reducing GRP78 and CHOP expression.
- OLE pretreatment ameliorated isoproterenol-induced cardiac dysfunction and damage in rats.
- OLE reversed the upregulation of GRP78 and CHOP in the in vivo model.
Conclusions:
- OLE and hydroxytyrosol demonstrate significant cardioprotective effects.
- The mechanism involves the modulation of endoplasmic reticulum stress pathways.
- Targeting ER stress presents a promising strategy for preventing and treating cardiovascular diseases.
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