# Antioxidant Activity of _Panax ginseng_ to Regulate ROS in Various Chronic Diseases
## 6 _P. ginseng_ in ROS-Mediated Diseases
### Antioxidant Activities of P. ginseng in Cardiovascular Diseases  
Cardiovascular disease (CVD) is a critical challenge among 50% of the world's population [118]. CVD includes hypertension, coronary artery disease, massive heart failure, and peripheral vascular disease, etc., which are common and affect newborns, children, and adults of both sexes [119]. Research shows that the enhancement of reactive oxygen species and oxygen consumption is one of the crucial factors in CVD outbreak. For example, heart failure can be caused by ROS-inducing cardiac apoptosis and necrosis [120; 121], as well as increased oxidant generation via the NADH/NADPH oxidant, and superoxide-generated endothelium breakdown results in hypertension and coronary artery disease [122; 123]; furthermore, an overproduction of ROS and oxidant-mediated myocyte apoptosis and necrosis causes myocardial infarction [124; 125]. An excessive amount of free oxygen from heart ischemia causes myocardial damage; however, ginseng consumption increases blood flow by inhibiting free oxygen and myocardial damage [126]. Ginsenoside Rb1 can inhibit the production of ROS to reduce homocysteine which causes endothelial dysfunction [127].  
Ginsenoside Re protects the myocardial cell from oxidative damage and increases myocardial cell viability in heart ischemia [128]. Total ginsenosides enhance coronary artery perfusion flow by activating the PI3K/Akt-eNOS signaling pathway that ultimately produces NO levels [129]. Ginsenoside-Rb1 administration increases eNOS expression which also increases NO levels and decreases super oxides in the porcine coronary artery via the vasodilating mechanism [127]. In addition, the saponin fractions of Korean red ginseng decrease blood pressure and prompt reflex tachycardia due to their hypotensive effect and the mechanism of NO donation [130]. In another study, total ginsenosides were effective against right ventricular hypertrophy, promoted systolic pressure, and reduced pulmonary pressure by controlling the ERK-1/MAPK signaling pathway [131]. [PERSON] et al. demonstrated that the consumption of PPT-rich ginseng enhances the activation of eNOS, stimulates NO formulation, and improves the thickness of the vessel walls to attenuate hypertension [132]. Previous studies have depicted that ginsenoside Rg1 inhibited Bcl-2 and caspase-3 expression during myocardial infarction via ischemia to lower myocardial cell death and decreased left ventricular hypertrophy [133]. In another study, ginsenoside CK reduced the burden of myocardial infarction by increasing the protein kinase B(Akt) and nitrogen oxide synthetase (eNOS) followed by ischemia via the Akt/PI3K pathway [134]. Although it has also been reported that ginsenoside Rg3 mitigates myocardial ischemia-reperfusion injury (MIRI) via the AKT/eNOS and Bcl-2/Bax signaling pathways [135], ginsenoside Rd reduces MIRI via the Nrf-2/HO-1 pathway [136], and ginsenoside Rb1 inhibits cardiomyocyte autophagy via the PI3K/Akt/mTOR pathway, thus controlling MIRI [137]. Recently, ref. [138] confirmed that ginsenoside Rh2 provides anti-inflammatory and antioxidant activity on MIRI via the regulation of the Nrf/HO-1/NLRP3 signaling pathway.