Cardiovascular Diseases and Panax ginseng: A Review on Molecular Mechanisms and Medical Applications
Posted by Michael Burmeister on
Ginseng is one of the most widely used herbal medicines and is reported to have a wide range of therapeutic and pharmacological applications. Ginseng may also be potentially valuable in treating cardiovascular diseases. Research concerning cardiovascular disease is focusing on purified individual ginsenoside constituents of ginseng to reveal specific mechanisms instead of using whole ginseng extracts. The most commonly studied ginsenosides are Rb1, Rg1, Rg3, Rh1, Re, and Rd. The molecular mechanisms and medical applications of ginsenosides in the treatment of cardiovascular disease have attracted much attention and been the subject of numerous publications. Here, we review the current literature on the myriad pharmacological functions and the potential benefits of ginseng in this area. In vitro investigations using cell cultures and in vivo animal models have indicated ginseng’s potential cardiovascular benefits through diverse mechanisms that include antioxidation, modifying vasomotor function, reducing platelet adhesion, influencing ion channels, altering autonomic neurotransmitters release, and improving lipid profiles. Some 40 ginsenosides have been identified. Each may have different effects in pharmacology and mechanisms due to their different chemical structures. This review also summarizes results of relevant clinical trials regarding the cardiovascular effects of ginseng, particularly in the management of hypertension and improving cardiovascular function.
Cardiovascular disease (CVD) is an important problem among the 400 million indigenous populations around the world, and have been included in the World Health Organization ‘2008-2013 Action plan for noncommunicable diseases’ . CVD, which encompasses a spectrum of diseases including coronary artery disease, peripheral vascular disease, congestive heart failure, dyslipidemias, and hypertension, affects millions of Americans and is perennial among the leading causes of morbidity and mortality . These diseases are common and occur in infants, children, and adults of both genders, affecting people of all races and ethnicities. The lifetime risk for a 40-year-old developing coronary heart disease is roughly 50% for men and 32% for women . Over the past 50 years, it has become clear that the cascade of thrombotic events following atherosclerotic plaque rupture causes occlusion of the coronary artery, which interrupts the supply of blood and oxygen to the myocardium, resulting in infarction. Myocardial necrosis following infarction is followed by heart failure, myocardial rupture, or arrhythmia . Despite enormous strides in the last five decades, myocardial infarction, stroke, and sudden death remain the principal causes of morbidity and mortality in industrialized nations. Among the most important of these CVD are dyslipidemia, hypertension, age, smoking status, insulin resistance, diabetes mellitus, and family history for premature coronary artery disease . Also, atherosclerosis and acute coronary syndrome are now recognized as manifestations of vascular inflammation [6,7]. Risk factors for CVD promote endothelial dysfunction. Dysfunctional endothelial cells express adhesion molecules, which promote the binding and influx of inflammatory white blood cells (T-cells and mast cells) into the subendothelial space . White blood cells produce interleukins, cytokines, and reactive oxygen species, which create an inflammatory focus within the arterial wall. Atherogenic lipoproteins such as low-density lipoprotein access the subendothelial space where they become trapped within the network of intercellular matrix proteins and undergo enzymatic oxidative modification, aggregation, and, ultimately, uptake by macrophages. This process leads to the development of foam cells [9,10]. Heart disease is the leading cause of death among all ages, and cardiac infarction remains the major cause of death (Fig. 1) [11,12]. This is the foremost reason why CVD is a major area of longevity research.
Ginseng has been used for over 2,000 years, in the belief that it is a panacea and promotes longevity. Panax ginseng is a traditional medicinal plant that has been used therapeutically for millennia in the Orient. Particularly in Korea, China, and Japan, it is the most valuable of all medicinal herbs. The name Panax means ‘all healing,’ which describes the traditional belief that ginseng has properties to heal all aspects of the body. The most common ginsengs are Korean red ginseng (P. ginseng Meyer), Chinese ginseng (P. notoginseng) and American ginseng (P. quinquefolium L.). Despite this rich history, the basis of the plant’s medicinal prowess was unknown until the isolation of the active constituents (ginsenosides) beginning in 1963 [13,14]. Much effort has since been focused on evaluating the function and elucidating the molecular mechanism of each ginsenoside. This is reflected in the exploding number of PubMed cited publications on ginseng and ginsenosides since 1975. Research now focuses on the study of purified individual ginsenosides instead of using whole ginseng root [15-20]. Each ginsenoside may have different pharmacologic effect(s) and mechanism(s) reflective of their different structures. Approximately 40 ginsenosides have been identified as of 2012, and the various methods of separation and analysis are well-reviewed . The most commonly studied ginsenosides are Rb1, Rg1, Rg3, Re, and Rd. A detailed review about the anti-amnestic and anti-aging effects and action mechanisms of Rb1 and Rg1 has been published .
Moreover, ginseng and its ginsenoside constituents are thought to possess vasorelaxation, anti-oxidation, anti-inflammation, and anti-cancer activities. Ginsenosides also showed the effects on the central nervous system and the peripheral nervous system . Furthermore, ginseng’s long-lasting prowess has been demonstrated as well as its enhanced benefit in a disease state than a healthy state [23-25]. Additionally, a previous study reported the molecular mechanisms and cardiovascular clinical applications of ginseng .
Koreans have traditionally used P. ginseng roots and root extracts to revitalize the body and mind, increase physical strength, prevent aging, and increase vigor. A new pharmacological concept of the tonic effect of ginseng has arisen , resulting in interest and attention by explaining the basic pharmacology of ginseng with adaptogen effects. Ginseng use is common in individuals who have cardiovascular risk factors, such as hypertension, hypercholesterolemia, and oxidative damage. Yet, its’ cardiovascular safety and efficacy are unclear. This review summarizes the current knowledge regarding the efficacy of ginseng on the major cardiovascular risk factors of blood pressure, cardiac ischemia, vasomotor activity, lipid profile, and oxidative stress.
Ginseng is a traditional herbal medicine whose history stretches back millennia. The basis of ginseng’s prowess is its’ many active constituent ginsenosides. Ginseng has extensive pharmacological activities and specific mechanisms of action. Ginsenosides can inhibit ROS production, stimulate NO production, increase blood circulation, ameliorate vasomotor tone, and adjust lipid profile. Additionally, many studies indicate that ginsenosides have a multitude of activities in both physiological and/or pathologic conditions concerning with CVD. How these effects relate to the ginsenoside structures are still not yet fully understood. Future cardiovascular studies involving each ginsenoside should include the mechanisms of action in more detail, with emphasis on specificity, structure and function relationship, detailed pharmacokinetics and toxicity researches, and therapeutic studies in both animal and human models.