Mitochondria as therapeutic targets for Natural Products in the treatment of Cardiovascular Diseases.

Ethnopharmacological Relevance: Natural products represent a unique medical approach to treating disease and have been used in clinical practice for thousands of years in cardiovascular disease (CVDs). In recent years, natural products have received increasing attention for their high efficiency, safety, and low toxicity, and their targeted regulation of mitochondria offers promising strategies for the treatment of CVDs. However, the potential mechanisms by which natural products target mitochondria for cardiovascular treatment have not been fully elucidated.

Aim Of The Study: The literature of the past decade is reviewed to emphasize the therapeutic efficacy and potential mechanisms of natural products targeting mitochondria for the treatment of CVDs.

Materials And Methods: In the NCBI PubMed database, relevant literature was searched using 'natural products', 'mitochondria' and 'cardiovascular disease' as search terms, and review papers were excluded. The remaining articles were screened for relevance. Priority was given to articles using rat models, in vivo, ex vivo or in vitro assays. The resulting articles were categorized into natural product categories, including saponins, alkaloids, plant extracts and preparations. This article reviews the research progress on mitochondria as potential therapeutic targets for CVDs and summarizes the application of mitochondria-targeted natural products in the treatment of CVDs.

Results: Mitochondrial damage attribute to impairment of biogenesis (mitochondrial number and mitochondrial DNA damage), dynamics disruption (mitophagy inhibition and overpromotion, fusion and fission), and optimal dysfunction (ATP generation, ROS production, fatty acid β oxidation, mitochondrial membrane permeability, calcium homeostasis imbalance, membrane potential depolarization). Mitochondrial dysfunction or damage lead to cardiomyocyte dysfunction, ion disorders, cell death, and ultimately CVDs, such as myocardial infarction, heart failure, ischemia reperfusion, and diabetic heart disease. Natural products, which include flavonoids, saponins, phenolic acids, alkaloids, polysaccharides, extracts, and formulations, are seen to have significant clinical efficacy in the treatment of CVDs. Mechanistically, natural products regulate mitophagy, mitochondrial fusion and fission, while improving mitochondrial respiratory function, reducing ROS production, and inhibiting mitochondria-dependent apoptosis in cardiomyocytes, thereby protecting myocardial cells and heart function.

Conclusions: In this paper, we reviewed the great potential and mechanism of natural products to regulate mitochondria for the treatment of CVDs, creating more opportunities for understanding their therapeutic targets and derivatization of lead compounds, and providing a scientific basis for advancing CVDs drug research.