# Bioactive Compounds and Nanodelivery Perspectives for Treatment of Cardiovascular Diseases
## 4 Therapeutic Effect of Bioactive Compounds on Cardiovascular System
### Flavonoids  
Randomized trials and many cohort studies have shown that flavonoids reduce CVD risk. Flavonoids produce a suitable response to LDL cholesterol, sensitiveness to insulin, and endothelial function [123]. A comprehensive evaluation of many investigations has indicated that the nutritional consumption of different groups of flavonoids, specifically as flavonoids, anthocyanins, proanthocyanidins, flavones, flavanones, and flavan-3-ols, minimize any chances of CVD drastically [124]. The quality of flavonoid subcategories in foods will be more essential than total flavonoids. Furthermore, the inverse correlationbetween flavonoid consumption and CVD risk is more pronounced in females than males. Even so, owing to the complementary nature of randomized clinical trials, there is indeed a lot of variance in the evidence [125]. Flavonoid research has exploded in popularity since its inception [126]. Understanding the availability of flavonoids, both natural and synthetic, and finding ways to improve their bioavailability were two of the most difficult tasks [127]. The scarcity of flavonoids is well known, but recently, these problems have been addressed. According to new research, the gut and its microbiome play a significant function in the development of prebiotic and microbiota enhancers as phenolic metabolites [128]. Flavonoids have been shown to reduce gastric and intestinal inflammation, as the metabolites act as enhancers of gut immune function [129]. As a result, attempts to increase flavonoids' bioavailability aiming primarily on increasing their intestinal absorption. Borneol and methanol combination are traditional drug absorption enhancers [130]. Both borneol and methanol are toxic, and methanol causes blindness [131, 132]. Effect on CV System  
Regarding antiatherosclerotic effects, the pathogenesis of atherosclerosis begins with the oxidative alteration of low-density lipoproteins (LDL) by free radicals. Foam cells develop when oxidatively modified LDL is rapidly absorbed through a scavenger receptor. They act as antioxidant-chain breaking, in which flavonoids are radical species [133]. The capacity of quercetin and quercetin glycosides to shield LDL from oxidative activation has been shown to be successful [134]. A Japanese study found an inverted relationship between the flavonoid consumption and total plasma cholesterol levels [135]. Regarding antithrombotic effects, platelet aggregation is critical in the composition of thrombotic disorders. Activated platelets bind to the vascular endothelium and develop lipid peroxides and oxygen free radicals, which prevent the formation of prostacyclin and nitrous oxide (NO) in the endothelium. Tea pigment shows the prevention of platelet adhesion or aggregation, and it reduces blood coagulation as well as increases fibrinolysis [136]. Flavonoids such as quercetin, kaempfer, and myricetin have been shown to inhibit platelet aggregation in animals [137]. Flavonols are particularly antithrombotic because they scavenge free radicals, keeping endothelial prostacyclin and nitric oxide concentrations constant [138]. Regarding cardioprotective effects, from both advanced and emerging economies, CVD is now the major cause of death. Atherosclerosis, coronary heart disease, arterial hypertension, and heart failure are all cardiovascular system (CVS) disorders. Oxidative stress is the primary cause of CVS disorders. Endogenous oxidants and reactive oxygen/nitrogen species (RONS) are in equilibrium in oxidative stress, with free radicals predominating. A prolonged dispensing of flavonoids has been shown to diminish or threaten to degrade the rate of CVD and its effects. They have an elevated inclination to transfer electrons, chelate ferrous ions, and sift reactive oxygen species [139]. Flavonoids are potential protectors against the persistent cardiotoxicity triggered by cytostatic medication such as doxorubicin [140, 141].