The herbal remedies referred to as “ginseng” are derived from the roots of several plants. Panax ginseng, usually known as Asian or Korean ginseng, is one of the most widely used and researched ginsengs. The main active components of Panax ginseng are ginsenosides, which have been demonstrated to provide a variety of beneficial effects, including anti-inflammatory, antioxidant, and anticancer effects .
Modern studies show that ginseng contains a large number of active ingredients, including ginsenosides, ginseng polypeptides, ginseng polysaccharides and others. Among them, ginsenosides, the standardized ginseng, are considered to be major active ingredients of ginseng physiological activity, which have impacts on the nervous system, cardiovascular system, and immune system . Ginsenosides are a group of triterpenoid saponins linked with sugar chain that can be divided into two types based on their structural differences: dammarane and oleanane. According to the positioning of sugar moieties at carbon -3 and -6, dammarane type ginsenosides can be classified into panaxadiol-type (PPD) group including Ra1, Ra2, Rb1, Rb2, Rb3, Rc,Rd, Rg3, etc., and panaxatriol-type (PPT) group including Rg1, Rg2, Re, Rf, Rh1, etc. Until now, more than 100 ginsenosides have been isolated and identified from the genus Panax, among these chemical compounds, the contents of Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1 contribute a lot in ginsenosides, with a proportion of more than 90 percent. Ginsenosides are found in other sections of ginseng besides the root, and their composition and concentration vary. The findings revealed that fine root had more ginsenoside content than other portions, meanwhile, Rb1 and Re, two individual ginsenosides, being the most abundant in the underground parts and the aboveground parts, respectively .
Ginseng polysaccharides, as another important bioactive component of ginseng, also have many biological activities, such as immune regulation, anti‐cancer, anti‐depression and anti‐oxidation .
EFFECTS ON PSYCHOLOGIC FUNCTION
- Antidepressant effect
Monoamine neurotransmitters have become a focus on the pathophysiology of depression. It is reported that depression is caused by a decline in the function of monoamine transmitters, such as serotonin (5‐HT), noradrenaline (NA) and dopamine (DA). In an experimental comorbidity model of myocardial infarction (Akbay’s model) and depression (modified forced swimming model), pretreatment with ginseng saponins, known as ginsenosides, may significantly increase the 5‐HT levels in both serum and platelets but not reverse the decline of 5‐HT level in the brain. So some studies have found that ginseng plays an important role in depression and could be used as an antidepressant. Furthermore, ginseng has a high safety profile and little side effects when taken for a long duration .
- Effect on memory, thinking, and other psychomotor functions
In one study of 112 healthy volunteers older than 40 years, the administration of 400 mg/day of the standardized ginseng for eight weeks resulted in better and faster simple reactions and abstract thinking, but no change in concentration, memory, or subjective experience .
The results of two small studies, each including about 30 young, healthy volunteers who received 200 mg of ginseng daily for eight weeks, showed improvement in certain psychomotor functions (i.e., better attention, processing, and auditory reaction time), social functioning, and mental health. However, some of the effects present at the fourth week disappeared by the eighth week .
EFFECTS ON CARDIOVASCULAR DISEASE
Cardiovascular diseases (CVDs) are a leading cause of death worldwide. CVDs are responsible for 42 percent of men’s deaths and 52 percent of women’s deaths in Europe. CVDs includes a number of diseases and conditions, such as coronary artery disease, heart attack, myocardial infarction, hypertension, and atherosclerosis .
- Cardio protection
Accumulating studies have revealed that ginsenosides have protective effect on heart failure, cardiac hypertrophy, cardiac fibrosis, cardiomyocyte apoptosis, hypoxia/reoxygenation (H/R) injury, and other cardiac dysfunction diseases. One study reported that endotoxin‑induced cardiomyocyte apoptosis and the inflammatory could be alleviated by notoginsenoside R1 though the activation of ERα. In recent years, a growing number of evidences suggested that ginsenosides have the therapeutic potential on H/R injury, and some key mechanisms were included such as inhibiting oxidative stress, autophagy, apoptosis, maintaining mitochondrial dynamics .
Numerous evidences ginsenosides have been shown to be effective in the treatment of hypertension in a numerous of studies. In one study, ginsenoside Rb3 was found to reduce oxidative stress and retain endothelial function in renal arteries from hypertensive rats. It’s reported that the endothelium lining the luminal surface of blood vessels contributes to the regulation of vascular tone. Ginsenosides Rb1 and Rg1 have been discovered to lower blood pressure via stimulating endothelial-dependent vascular dilatation .
- Anti-atherosclerosis effect
Atherosclerosis gives rise to cerebrovascular diseases through a slowly progressing lesion formation and luminal narrowing of arteries. Both animal and cell models of atherosclerosis have been used to assess the therapeutic potential of ginsenosides in vivo and in vitro, with similar results .
Adaptogens are incredible natural substances that assist the body in adapting to stress, maintaining or normalizing metabolic functioning, and restoring systemic balance. They enhance the resistance against acute of chronic stress and several other stressors (e.g., biological, physical, emotional and environmental) .
Antiplatelet and antithrombotic effects have been discovered in Panax ginseng and many ginsenosides. The pharmacological and therapeutic effects of Panax ginseng and its ginsenosides on vascular endothelial cells and platelets have a lot of similarities and differences, which could imply that it has adaptogenic qualities .
An interesting and classical example is that Panax ginseng or ginsenosides cause vasorelaxation by NO production through stimulation of the eNOS-PI3K/Akt pathway in vascular endothelial cells but produce antiplatelet and antithrombotic effects by inhibiting the PI3K/Akt pathway .
EFFECTS ON DIABETES
Type 1 diabetes, which is characterized by insulin deficiency, and type 2 diabetes, which is characterized by insulin resistance, are the two most common types of diabetes. The majority of diabetes is type 2 diabetes, there is also a huge population with prediabetes, which is very likely to develop into type 2 diabetes. Diabetes, especially diabetic complications, can cause major health concerns if not properly managed .
Ginsenosides are an important class of natural triterpene saponins, which are thought to be responsible for the anti-diabetic effect in ginseng. The majority of ginsenoside investigations have focused on Rb1, Re, or Rg1, which are the primary components of ginseng and are easily obtained. Although the anti-diabetic mechanism of ginseng is not completely understood, the available evidence suggests that the regulation of blood glucose by ginseng is possibly related to the following four aspects. First, ginseng modulates blood glucose levels by improving β-cell function and enhancing insulin sensitivity. Second, ginseng can enhance glucose uptake by up-regulating the expression of glucose transporters (GLUT). Third, treatment with either ginseng polysaccharides in streptozotocin induced diabetic mice or ginsenoside Rg1 in streptozotocin induced diabetic rats was shown to suppress of oxidative stress through increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) production. Finally, ginsenosides regulate blood glucose in diabetic mouse or rat models, accompanied by regulating the expression of TNF-α, eNOS, suggesting that diabetes is associated with inflammation, and effective modulation by ginseng on inflammation may be able to prevent the development of insulin resistance .
The effects of Panax ginseng, given in a dosage of 100 or 200 mg/day for eight weeks, were studied in 36 patients with newly diagnosed non–insulin-dependent diabetes. Improved fasting blood glucose levels, improved mood, and improved psychophysical performance on a numbered diagram test were all found in the study. The 200-mg dose also resulted in improved hemoglobin A1C values .
EFFECTS ON IMMUNE SYSTEM
Based on extensive in vitro and in vivo studies, the main activities of ginseng can be summarized as follows: immune stimulation, increased antitumor activity, improved cardiovascular function (vasodilation and reduced platelet aggregation), antioxidant activity (increased oxygen radical scavenging and decreased lipid peroxidation), hypoglycemicactivity, and stimulation of the pituitary adrenocortical system (steroidal effect). Many ginsenosides are antioxidants that protect cell membranes, notably those of neuron and immune cells .
A 12-week trial of 227 healthy volunteers found that taking 100 mg of ginseng daily improved the efficiency of a polyvalent influenza vaccine. Patients who took ginseng had a lower incidence of influenza and colds, higher antibody titers, and higher natural killer cell activity levels. Another study of 60 healthy volunteers found that individuals who took 100 mg of ginseng twice daily for eight weeks had improved chemotaxis, phagocytosis, total lymphocyte count, and T helper cell numbers. In a study of 75 patients with acute exacerbation of chronic bronchitis who were treated with antibiotics or antibiotics plus ginseng, those in the ginseng group showed faster bacterial clearance .
EFFECTS ON PHYSICAL PERFORMANCE
Fatigue, which is a lack of energy and motivation, is a common and important response to physical activity, emotional stress, boredom, or lack of sleep. Physical performance relates to the ability to complete certain physical tasks with higher intensity, faster, or with a higher power output. Several randomized controlled trials (RCTs) have demonstrated the effectiveness of ginseng supplements in reducing fatigue and improving physical performance. However, those findings remain inconsistent .
A meta-analysis of RCTs indicated that ginseng supplements were effective in reducing fatigue but not in improving physical performance. The efficacy of ginseng supplements on mental and physical fatigue reduction and physical performance enhancement may be due to a variety of biological factors. Regarding mental fatigue, although a human study indicated that ginseng increases cognitive performance, its mechanisms remain not known, but may be related to the ginseng’s glycemic properties. As for physical fatigue and physical performance, ergogenic aids are believed to increase performance by some of the following mechanisms: renewing or increasing energy stores in the body, facilitating the biochemical reactions that yield energy, reducing or neutralizing performance-inhibiting metabolic by products, and facilitating recovery .
ADVERSE EFFECTS, DRUG INTERACTIONS, AND CONTRAINDICATIONS
Panax ginseng is generally well tolerated, and its adverse effects are mild and reversible. Associated adverse effects include nausea, diarrhea, euphoria, insomnia, headaches, hypertension, hypotension, mastalgia, and vaginal bleeding .
Panax ginseng may cause hypertension when used with caffeine, and it may also help to reduce blood alcohol levels. It also has the potential to reduce the effectiveness of warfarin. Manic-like symptoms may occur if Panax ginseng and the monoamine oxidase inhibitor phenelzine are taken together .
Ginseng also causes hypoglycemic activity, and caution should be exercised in using ginseng products in patients with diabetes because of possible interactions with oral hypoglycemic agents and insulin. Children and pregnant or breastfeeding women should avoid ginseng products, until more comprehensive studies verify their safety in these groups .
Contraindications to the use of Panax ginseng include high blood pressure, acute asthma, acute infections, and nose bleeds or excessive menstruation. These effects appear to occur primarily with high dosages or prolonged use .
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