Study on Ginseng Extract Ginsenoside Antioxidant

Oxidative stress refers to a state in which the balance between oxidation and anti-oxidation in the body is disrupted, and oxidation prevails, leading to the accumulation of free radicals in the body, infiltration of inflammatory cells, excessive secretion of proteases and production of oxidative intermediates, causing cell damage and apoptosis. This is a kind of adverse reaction that can further induce aging of the body and the development of various acute and chronic diseases. In recent years, some scholars have found that oxidative stress plays a role in the occurrence and development of tumors. It can induce DNA mutations in cells, mediate the activation and inactivation of proto-oncogenes and tumor suppressor genes, and cause abnormal cell proliferation, leading to the occurrence of tumors [1]. In addition, it can also induce the metabolism of tumor cells by inducing key metabolic enzymes, genome changes related to metabolism, and activating signal pathways, thereby promoting the further development of tumors [2].

Ginseng extract ginsenosides are one of the main active ingredients in ginseng. There are currently dozens of known ginsenosides, among which Rb1 and Rg1 play an important role in antioxidant stress and have great potential in the treatment of oxidative stress-mediated diseases.

1 Ginsenoside Rb1 antioxidant stress effect

Ginsenoside Rb1 is a tetracyclic triterpene saponin with central nervous system depressant and sedative effects. It is one of the main ingredients in ginseng with antioxidant stress effects. Intermittent high glucose (IHG) increases the activity of xanthine oxidase in cells, which in turn produces a large amount of reactive oxygen species (ROS). Studies have shown that ginsenoside Rb1 can effectively inhibit the increase in ROS and 8-hydroxydeoxyguanosine caused by IHG, thereby reducing oxidative stress in cells and improving diabetic peripheral neuropathy [3]. 8-Hydroxydeoxyguanosine is a marker of oxidative damage to DNA caused by endogenous and exogenous factors [4]. Under conditions of ischemia and hypoxia in cardiomyocytes, the function of the body's antioxidant system decreases, and the activity of the system that produces ROS increases (e.g., the amount of malondialdehyde produced increases). When blood and oxygen supply to the tissue is restored, there is an explosive growth of oxygen free radicals.

Studies have found that ginsenoside Rb1 pretreatment can reduce malondialdehyde expression, increase SOD activity, and reduce ROS levels in H9c2 cells subjected to ischemia/reperfusion (I/R), as well as the expression of caspase-3 and the number of apoptotic cells. It can also reduce oxidative stress damage and apoptosis in H9c2 cardiomyocytes subjected to I/R, and plays a protective role in H9c2 cardiomyocytes [5]. In addition, PI3K/Akt plays an important role in angiogenesis. After phosphorylation, it can activate nitric oxide synthase (NOS) to produce NO, which has the effect of protecting the survival of vascular endothelial cells and the heart [6].

Some studies have suggested that ginsenoside Rb1 may reduce I/R injury by activating the PI3K/Akt signaling pathway [7]. Ginseng saponin Rb1 activates the Gβ1/PI3K/Akt-Nrf2 signaling pathway, which, under the induction of estrogen receptor-dependent heme oxygenase 1 (HO-1), enhances the antioxidant defense capacity of cells, thereby protecting cells from oxidative stress damage [8]. Among these, Nrf2 is a key factor in the cell's oxidative stress response, regulated by Keap1, which regulates the expression of antioxidant proteins and phase II detoxification enzymes by interacting with the antioxidant response element ARE [9].

Excessive production of ROS in skeletal muscle is one of the important causes of skeletal muscle fatigue. During the perioperative period, anesthesia, surgical trauma and other factors induce the production of ROS, which exceeds the body's ability to remove it, leading to skeletal muscle fatigue. Mao Xiangyu [10] and others found that ginsenoside Rb1 can alleviate oxidative stress damage to skeletal muscle in elderly rats with postoperative fatigue syndrome by activating the Nrf2/ARE pathway, thereby achieving the effect of preventing postoperative fatigue. This is consistent with the results of other studies [11]. In addition, when a large number of oxygen free radicals are produced in the body, the level of oxidative stress in cells increases, the lipids in the cell membrane are peroxidized, the permeability of the cell membrane increases, which in turn causes a large influx of extracellular calcium ions, and calcium overload occurs in the cell, leading to cell damage and apoptosis [12]. Li Ying [13] and others found that ginsenoside Rb1 can effectively reduce the Ca2+ level in retinal ganglion cells (RGC) under oxidative stress, antagonizing the oxidative damage induced by H2O2 in RGC-5 cells. In addition, ginsenoside Rb1 can also protect human umbilical vein endothelial cells from TNF-α-induced oxidative stress and inflammatory damage by inhibiting nuclear factor kappa-B (NF-κB) signaling and downregulating the expression of inflammatory factors and apoptosis-related proteins [14].

2 Ginsenoside Rg1's antioxidant stress effect

Ginsenoside Rg1 is a tetracyclic triterpene saponin that has the effects of promoting hippocampal neurogenesis, enhancing learning and memory, anti-aging, anti-fatigue, improving immunity, assisting in anti-tumor, and repairing sexual function. It is one of the main components of ginseng with antioxidant stress effects. Studies have shown that ginsenoside Rg1 can protect hippocampal neural stem cells from damage by indirectly inhibiting the P53-P21 signaling pathway, thereby delaying brain aging and improving learning and memory abilities [15]. Ginsenoside Rg1 enhances the ability of the enzymatic antioxidant system, reduces the level of oxidative stress, further reduces the activity of the Akt/mTOR signaling pathway in neural stem cells treated with D-galactose, and downregulates the levels of downstream p53, p16, p21, and Rb genes, thereby delaying cognitive decline in mice and protecting neural stem cells [16].

Another study found that ginsenoside Rg1 can antagonize D-galactose-induced spleen and thymus damage in senescent rats by reducing oxidative stress damage and downregulating the expression of aging-related proteins [17]. Studies have shown that the expression and activation of the RhoA protein and Rho kinase can inhibit the expression of NOS in endothelial cells [18]. Ginsenoside Rg1 can bind to RhoA, downregulate the activity of the RhoA signaling pathway, and restore ATP production in the heart, thereby protecting against I/R-induced myocardial injury [19].

Ginsenoside Rg1 can effectively inhibit the intracellular calcium overload caused by elevated ROS and inhibit apoptosis of nerve cells caused by oxidative stress, thereby reducing cerebral ischemia injury [20]. SIRT1 is a homolog of the yeast chromatin silencing factor SIRT2 that is present in mammals and has the highest homology. It is involved in the regulation of many physiological functions in the body, including the regulation of oxidative stress processes. Ginseng saponin Rg1 can enhance the expression of SIRT1 in Sca-1HSC/HPC. The increased SIRT1 further inhibits the expression of the downstream regulatory molecule NF-κB. that ginsenoside Rg1 can delay the aging of Sca-1HSC /HPC in a rat aging model induced by D-galactose by regulating the SIRT1-NF-κB signaling pathway [21].

In addition, ginsenoside Rg1 can also inhibit cell damage caused by oxidative stress by regulating the FoxO3a-related signaling pathway [22]. Ginsenoside Rg1 causes the nuclear translocation of Nrf2 and enhances downstream HO-1 expression in a dose-dependent manner, i.e., activating the Nrf2/HO-1 axis and inhibiting the JNK pathway in H9c2 cells to prevent oxidative stress [23]. Some research results show that Rg1 is an effective activator of peroxisome proliferators-activated receptors (PPARγ). It can alleviate oxidative damage in the body by upregulating PPARγ expression and increasing the levels of SOD and GXH-Px in the body [24].

In summary, ginsenosides have antioxidant properties and are involved in a wide variety of proteins and signal pathways that are involved in antioxidant stress. Research on whether ginsenosides can inhibit the occurrence and development of tumors by inhibiting oxidative stress in cancer cells and the mechanism of action will provide a new way of thinking for the treatment of cancer.

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