Study on Ginseng Extract Ginsenoside Anti-Fatigue

The active ingredients of ginseng mainly include ginsenosides, ginseng polysaccharides, peptides, alkaloids, etc. [1]. Ginsenosides are the main active ingredients of ginseng. The ginsenosides that have been isolated and identified are mainly divided into three categories: ginsenodiol type (damarane A type), ginsenoside type (damarane B type), and oleanolic acid type. Among them, 123 ginsenoside monomers have been discovered and reported [2]. At present, research on ginsenoside monomers is mainly focused on the cardiovascular system, nervous system, anti-diabetes, anti-tumor and other fields [3-6], while research on the anti-fatigue effect is relatively rare, and it mainly focuses on four ginsenoside monomers, namely Rb1, Rg3, Rg1 and Ro, as summarized below.

1 Ginsenoside Rb1

Postoperative fatigue syndrome (POFS) is a common clinical complication, especially after abdominal surgery. The incidence and intensity of postoperative fatigue significantly increase during the first month after surgery, and fatigue symptoms may even persist for up to one year after surgery [7-8]. Relevant animal experiments have found that surgical trauma stress can inhibit the expression of nerve growth factors in rats, causing damage to hippocampal neurons and resulting in decreased activity, learning and memory abilities, and mental mood in rats [9]. and hippocampal neurotrophic factor are the main neurotrophic factors. Ginseng saponin Rb1 can promote the expression of hippocampal neurotrophic factor and brain-derived neurotrophic factor mRNA in the hippocampus, upregulate the transcription of neurotrophic factor mRNA, promote nerve damage repair in rats, and alleviate central fatigue caused by POFS through neural tissue regeneration and repair [9].

Related experimental studies have found that surgical trauma stress can also activate inflammatory signaling pathways such as p38 mitogen-activated protein kinase and nuclear transcription factor-κB, and increase the transcriptional level of inflammatory factors in the hippocampus of POFS rats, resulting in significant central inflammation and central fatigue. The application of ginsenoside Rb1 can downregulate the expression of inflammatory factors in POFS rats, (nuclear transcription factor-κB/p65 nucleus) / (nuclear transcription factor-κB/p65 cytoplasm) was significantly reduced, and the expression of phosphorylated p38 protein was also significantly reduced, which significantly inhibited the relevant inflammatory pathways in the central nervous system and improved central fatigue [10]. Upregulation of the expression of the inflammatory cytokines interleukin-6, interleukin-1β and tumour necrosis factor-α can activate indoleamine 2,3-dioxygenase, which affects the metabolism of tryptophan in the brain, thereby stimulating NMDA receptor-mediated damage to hippocampal neurons. Chen et al. [11] showed that ginsenoside Rb1 can protect hippocampal neurons in rats by preventing the expression of inflammatory cytokines and NMDA receptors, thereby minimizing central fatigue. Ginsenoside Rb1 can also reduce oxidative stress damage by enhancing the activity of two antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase, and improve central fatigue symptoms by protecting central neurons [12].

Tan Shanjun et al. [13] and Mao Xiangyu et al. [14] found in their experiments that giving ginsenoside Rb1 can significantly reduce the content of malondialdehyde in the skeletal muscle of POFS rats, increase the activity of SOD, block peroxide reactions, and activate the Nrf2/ARE pathway, resulting in a significant increase in the expression of Nrf2 and Nqo1 after surgery, relieve fatigue caused by oxidative stress damage in the skeletal muscle of POFS elderly rats. In addition, ginsenoside Rb1 can also improve fatigue symptoms and the progression of the disease by increasing the ATP content in rat skeletal muscle, enhancing the activity of the energy metabolism enzyme Na + -K + -ATPase in skeletal muscle, activating the PI3K/Akt pathway, and increasing the expression of Akt2 and Nrf2 [15-16].

Lin et al. [17] showed that ginsenoside Rb1 can selectively block L-type calcium channels. It reduces Ca2+ influx, decreases the intracellular Ca2+ concentration, and is important for reducing myocardial contractility. It also helps protect the heart muscle of patients with exercise-induced fatigue. In addition, a decrease in intracellular Ca2+ concentration is conducive to the expulsion of Ca2+ from mitochondria, reduces the accumulation of free radicals, and is conducive to the recovery from exercise fatigue.

2 Ginseng saponin Rg3

Zhang et al. [18] found that compared with a water-soluble ginsenoside Rg3 solution, the 20(R)-ginsenoside Rg3-containing chitosan microspheres group significantly increased the time of swimming with a load in mice after administration, and the blood lactate and blood urea nitrogen levels in the microspheres group were significantly lower, while the liver glycogen and lactate dehydrogenase levels were significantly higher, suggesting that 20(R) -ginsenoside Rg3 in chitosan microspheres can have a better inhibitory effect on fatigue by prolonging the residence time of Rg3 in the nasal cavity and enhancing absorption by the nasal mucosa.

Research results show that in normal and simulated high-altitude environments, ginsenoside Rg3 can increase the total serum cholesterol, triglycerides, and lactate dehydrogenase concentrations of rats, as well as increase the blood glucose concentration of rats, and significantly increase the activity of skeletal muscle mitochondrial Mn-SOD and the activity of skeletal muscle mitochondrial respiratory chain complexes III and IV, and reduce the urea nitrogen and malondialdehyde content of rats in the hypoxia model. Therefore, the anti-fatigue mechanism of ginsenoside Rg3 is mainly related to maintaining blood glucose levels, improving the energy supply efficiency of skeletal muscle mitochondria, and accelerating free radical scavenging [19]. Yang et al. [20] found that ginsenoside Rg3 not only up-regulates serum total cholesterol, triglyceride, and low-density lipoprotein concentrations, but also increases SOD activity in skeletal muscle, reduces the release of malondialdehyde, enhances the expression of peroxisome proliferator-activated receptor γ coactivator-1α and phosphoenolpyruvate carboxykinase mRNA, activates silent information regulator 1, and concentration-dependently inhibits the transcriptional activity of p53, thereby exerting an anti-fatigue effect.

Animal experiments have shown that fatigue caused by forced swimming in mice under load can cause a decrease in dopamine levels in the brain, which is related to the decreased expression and phosphorylation of tyrosine hydroxylase. Ginseng saponin Rg3 can activate signal pathways such as PKAα, ERK1/2, Akt and α-synuclein, increase the expression and phosphorylation of tyrosine hydroxylase, raise dopamine levels in the brain, and significantly prolong the duration of swimming under load in mice, exerting an anti-fatigue effect [21].

3 Ginseng saponin Rg1

Song and Liu [22] found that ginseng saponin Rg1 can effectively improve the symptoms of chronic fatigue syndrome in rats by gastric infusion. The ginseng saponin group and the ginseng saponin plus exercise group can significantly reduce the content of lipid peroxide malondialdehyde in chronic fatigue syndrome rats, while enhancing the activity of the antioxidant enzyme SOD, indicating that ginsenoside Rg1 can improve the activity of the antioxidant enzyme system in the brain tissue of rats with chronic fatigue syndrome and reduce the accumulation of lipid peroxide metabolites, and has a good anti-fatigue effect. Wang Ying et al. [23] showed that ginseng saponin Rg1 at different doses, when administered to mice by gavage, significantly prolonged the time to exhaustion in swimming in the 5 mg/kg dose group, reduced serum urea nitrogen levels, maintained blood glucose levels, and increased muscle glycogen and liver glycogen reserves.  The 20 mg/kg dose group significantly reduced the blood lactate concentration after exercise, indicating that ginsenoside Rg1 has a significant anti-fatigue effect, and the low-dose group has a better effect. Ginsenoside Rg1 exerts its anti-fatigue effect mainly by accelerating the free radical scavenging rate, enhancing the activity of the antioxidant enzyme SOD in the body, maintaining blood glucose levels, and promoting glycogen synthesis.

4 Ginsenoside Ro

Ma, etc. [24] proved that ginsenoside Ro, successfully isolated using liquid chromatography-mass spectrometry, increased grip strength and endurance swimming time after acute exercise challenges in a dose-dependent manner when rats were fed doses of 0, 5 mg/(kg·d) and 25 mg/(kg·d) for 4 weeks. and creatinine and triglyceride levels were significantly reduced, while total protein, glucose levels and gastrocnemius muscle glycogen content were significantly increased. This is the first report of ginsenoside Ro from Panax ginseng extract supplement improving exercise performance, enhancing energy utilization and reducing relevant fatigue parameters in vivo.

5 Summary

With increasing social pressure, fatigue has become a common and widespread social phenomenon that seriously affects people's physical and mental health. The prevalence of fatigue is significantly higher in neurological diseases, especially in multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, traumatic brain injury, stroke, cerebral hemorrhage, and neuromuscular diseases. Fatigue is also affected by training, psychological preprocessing, and drugs, so it needs to be considered an important symptom [25].

In the research on fatigue mechanisms by scholars at home and abroad, the representative and more widely accepted mechanisms are the central fatigue theory, the energy substance depletion theory, the blockage or suffocation theory, the internal environment stability disorder theory, the mutation theory, the endocrine system disorder theory, and the free radical theory. Each theory reveals the cause of fatigue from a different perspective [26]. The main active ingredient in ginseng, ginsenoside, has anti-fatigue effects, including resistance to peripheral fatigue and central fatigue, which are mainly related to regulating glucose metabolism, reducing lactic acid accumulation, resisting free radicals, regulating neurotransmitters, regulating Ca2+ metabolism, inhibiting inflammatory factors, regulating signal pathways and neurotrophic factors, and anti-oxidative stress.

Fatigue, as a physiological or pathological response, requires further research into its pathogenesis, causes, assessment and treatment, and apply all available techniques to understand how central nervous system factors and peripheral nervous system factors affect fatigue. It is also important to determine relevant empirical standards to grade and monitor fatigue caused by diseases of different systems, such as exercise-induced fatigue, POFS, chronic fatigue syndrome, and cancer-related fatigue. This will allow the anti-fatigue effects of ginsenoside monomers to be better applied clinically, and strategies for treating fatigue will be developed based on theoretical and empirical research.

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