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Review
. 2020 Oct 28;13(1):49-63.
doi: 10.1016/j.chmed.2020.09.002. eCollection 2021 Jan.

Flavonoids in myocardial ischemia-reperfusion injury: Therapeutic effects and mechanisms

Jun-Ying Jia  1 , Er-Huan Zang  2 , Li-Juan Lv  3 , Qin-Yu Li  2 , Chun-Hua Zhang  2 , Ying Xia  4 , Lei Zhang  5 , Lian-Sheng Dang  6 , Min-Hui Li  2   4   5   7
Affiliations
Review

Flavonoids in myocardial ischemia-reperfusion injury: Therapeutic effects and mechanisms

Jun-Ying Jia et al. Chin Herb Med. .

Abstract

Ischemic heart diseases are one of the major causes of death worldwide. Effective restoration of blood flow can significantly improve patients' quality of life and reduce mortality. However, reperfusion injury cannot be ignored. Flavonoids possess well-established antioxidant properties; They also have other benefits that may be relevant for ameliorating myocardial ischemia-reperfusion injury (MIRI). In this review, we focus on flavonoids with cardiovascular-protection function and emphasize their pharmacological effects. The main mechanisms of flavonoid pharmacological activities against MIRI involve the following aspects: a) antioxidant, b) anti-inflammatory, c) anti-platelet aggregation, d) anti-apoptosis, and e) myocardial-function regulation activities. We also summarized the effectiveness of flavonoids for MIRI.

Keywords: anti-apoptosis; anti-inflammation; antioxidant activity; flavonoids; myocardial ischemia-reperfusion injury.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Process of ischemia–reperfusion injury.
Fig. 2
Fig. 2
Skeleton structures of active flavonoids. A: flavones; B: flavonols; C: isoflavones; D: flavanols; E: flavanonols; F: anthocyanins; G: flavanones.
Fig. 3
Fig. 3
Steps involved in the oxidative stress processes and cardioprotective properties of flavonoids. Flavonoids can be formed into inert compounds with metal ions to block the production of free radicals and can be antioxidant by blocking lipid peroxidation and inhibiting NADPH oxidase.
Fig. 4
Fig. 4
The mechanisms of flavonoids in inflammatory and platelet aggregation-mediated ischemia–reperfusion injury. Flavonoids have anti-inflammatory effects mainly by affecting the secretion process and intercellular interactions of cells. Flavonoids play an anti-platelet aggregation effect mainly by inhibiting cyclooxygenase, reducing the generation of TXA2 and blocking TXA2 receptor, but also by reducing oxidative stress, reducing calcium overload.
Fig. 5
Fig. 5
Action mechanism of flavonoids in anti-apoptotic myocardial ischemia–reperfusion injury. Flavonoids inhibit caspase-3 and Bax activities, promote Bcl-2 expression, enhance cardiac contractile protein expression, reduce cytotoxicity, and improve cardiomyocyte viability by restoring the decrease in the phosphorylation of AKT, P70S6K, and ERK1/2. It can also inhibit the harmful effects of electron transport chain complex II (ETC-II), and MAO-A can inhibit cardiomyocyte apoptosis. Flavonoids can also reduce the release of cytochrome C during MIRI, stabilise mitochondrial membrane potential, and inhibit cardiomyocyte apoptosis.
Fig. 6
Fig. 6
Action mechanism of flavonoids in regulating myocardial function. Flavonoids inhibit caspase-3 and Bax activities, promote Bcl-2 expression, enhance cardiac contractile protein expression. By activating the p-JAK2 and STAT3 signalling pathways, regulating the cardiac function indicators such as left ventricular ejection fraction, left ventricular end diastolic diameter, cardiac output, and contractile function.
Fig. 7
Fig. 7
Flavonoid compound-target-pathway-experimental model network.
See this image and copyright information in PMC

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