Which are the commonly used natural anti-oxidants?

joanna.jia@wecistanche.com / WhatsApp: 008618081934791

Research Of The Potential Anti-radiation Agents

Natural antioxidant - Curcumin

In a recent study, Soltani et al. [22] investigated the use of free curcumin and a novel endosomal nanoformulation of curcumin (DNC) in human leukemia cells. Prior studies have indicated that high concentrations of curcumin may induce apoptosis in human leukemia cell lines via activation of JNK/ERK/AP1 pathways. Interestingly, curcumin is believed to be an antioxidant at lower concentrations and a pro-oxidant at higher concentrations [22]. The authors of this study found that pretreatment of lymphocytes with low concentrations of free curcumin had a protective effect on irradiated cells via enhanced antioxidant effects. However, low concentrations of DNC lead to decreased cell viability and survival [22]. The authors concluded that low concentrations of free curcumin protected cells from radiation via increased scavenging of free radicals, activation of Nrf2 pathway (thus leading to increased expression of total antioxidant and thiol levels), and upregulation antioxidant gene expression [22]. Meanwhile, DNC induced apoptosis [22]. Another study looking at curcumin on irradiated lymphocytes, Srinivasan et al. [23] also found that there was a significant decrease in lipid peroxidation in all groups pretreated with curcumin, and significant increases in reduced glutathione. Both effects were dose-dependent: they were most pronounced in the highest concentration pretreatment groups [23]. Pretreatment with curcumin also leads to a significant increase in the activities of superoxide dismutase, catalase, and glutathione peroxidase after gamma-irradiation [23]. Not only did curcumin show significant anti-oxidative and anti-lipid peroxidative properties, but pretreated groups were found to have less overall DNA damage [23]. Given the reduced lipid peroxidation, improved antioxidant status, and reduced DNA damage in curcumin pretreated groups, the authors concluded that curcumin may induce the transcriptional factors for oxidative stress-related gene expression [23]. These studies support using certain curcumin analogs for mitigating the deleterious effects of radiation.

Cistanche has anti-aging, antioxidant, and skincare effects

Although curcumin is widely accepted as a radioprotectant, its clinical application is hampered due to its limited bioavailability. Nguyen et al. [24] used B-encapsulated liposomes to deliver Bto 60cobalt gamma radiation-damaged human lymphocytes and found that the curcumin-encapsulated liposomes had a dose-dependent radioprotective effect, with higher doses of curcumin being more radioprotective up to 30 μg/mL [24]. These investigators concluded that encapsulation with liposomes could increase the bioavailability of curcumin adding to its clinical use and may be effective as a delivery system for other radioprotective phytochemicals. Kalpana et al. [25] investigated the use of a dendrodoine analog (DA), derived from marine alkaloids extracted from the tunicate Dendrodoa grossularite. DA has been reported to be cytotoxic to lymphoma cells in culture, and it also contains aminothiazole compounds which have anti-tumor and antioxidant properties. The investigators incubated lymphocytes with differing concentrations of DA and then exposed them to X-rays. Compared to the control groups DA treated groups had less DNA damage and lipid peroxidation [25]. The authors concluded that this action was likely through the antioxidant effects of DA; however, the exact mechanisms by which DA acts are still unknown [25]. Since this study showed that human lymphocytes cultured in the presence of DA suffered less radiation-induced damage, DA is a potential candidate for pretreatment before ionizing radiation exposure.

Natural antioxidant - Green tea

Many researchers have focused on compounds found in plants and phytochemicals (in addition to curcumin and others discussed) as potential radioprotectants against ionizing radiation. In one study, Davari et al. [26] collected blood from volunteers who drank green tea for five consecutive days prior to blood draws. The whole blood sample was then exposed to gamma radiation. It was found that the lymphocytes collected 3 h after drinking green tea showed a significant decrease in DNA damage compared to controls [26]. Prasad et al. [27] explored the effects of ferulic acid on cultured lymphocytes. These investigators exposed lymphocytes pretreated with varying concentrations of ferulic acid to gamma radiation and found that the treatment with ferulic acid for 30 min prior to radiation exposure resulted in a significant reduction in DNA damage compared to non-treated controls and that higher concentrations provided more protective effects [27]. Ferulic acid was proposed to work by preventing a radiation-induced decrease in the activity of superoxide dismutase, catalase, and glutathione reductase [27]. Rodeiro et al. [28] conducted a study on the extract of Mangifera indica L. (mango) to evaluate its potential radioprotective effects in human lymphocytes. The lymphocytes were incubated with varying concentrations of Mangifera indica L. extract followed by exposure to gamma rays. Incubation of lymphocytes with Mangifera indica L. extract 1 h before exposure to gamma radiation reduced DNA damage [28]. This list is not all-inclusive but rather suggests that plants and phytochemicals could be a rich source of potential radioprotectants. A wide array of agents has been shown to decrease radiation-induced DNA damage in human lymphocytes. While many of these agents may ultimately have clinical value, it has not been definitively established that decreasing DNA damage in WBCs leads to clinical significant benefits. Future research, particularly long-term trials, will be necessary to demonstrate any concrete clinical benefit related to radioprotective agents.

Although most studies investigating radioprotective effects have been conducted on human lymphocytes in vitro, many studies have also been done on other non- lymphocyte human cell types. For example, Monzen et al. [29]performed a study in which they isolated CD34+cells and separated them into granulocyte and erythroid precursors. The cells were then pretreated with epigallocatechin-3-gallate (EGCg) prior to irradiation. EGCg is a natural antioxidant found in most teas. The addition of EGCg before irradiation significantly improved the survival of erythroid progenitors at low radiation doses; however, the same effects were not observed in granulocyte precursors [29]. These findings suggest that a low concentration of EGCg provides more protection from radiation damage in erythropoiesis than granulopoiesis. The authors reported that EGCg works as an antioxidant by trapping free radicals thus preventing lipid per- oxidation and DNA damage [29]. These findings suggest that EGCg may work particularly well with hematopoietic recovery after irradiation, and maybe a more cost-effective treatment than currently available medications [29]. Prior studies have shown that after drinking 1–2 cups of tea, the mean peak plasma EGCg level was like the concentrations used for their study, supporting simple dietary modifications as a means of radioprotection [29]. This observation is broadly applicable to other anti-oxidants: they are readily available in healthy diets, an observation that underscores the value of good nutrition to those undergoing radiation exposure.

Natural antioxidant - Green tea

Natural antioxidant - Resveratrol

Resveratrol is a known antioxidant and free radical scavenger and is also known to have significant cell cycle effects, including stabilization of p53 and alterations of pro-and anti-apoptotic protein concentrations [30, 31]. One study found resveratrol to have a pro-apoptotic effect on leukemia, mammary, and epidermoid cell lines, and growth-inhibitory activity in some human cancer cell lines [32]. Firouzi et al. [30] found that when resveratrol was administered before radiation, DNA damage and colony death were increased in resveratrol-treated glioblastoma cells relative to controls. Firouzi et al. [30] further showed that resveratrol binds to HIF1-α in hypoxic conditions (often found in neoplastic growth), leading to stabilization of p53 and decreased function of the vasculogenic VEGF [30]. In other words, resveratrol decreased new vascular growth to the glioblastoma cells while simultaneously stabilizing intra-cellular mechanisms for detecting and killing genetically mutated cells. The mechanisms for increased cell death described by Firouzi et al.[30] are complemented by effects described by Carsten et al. [31] who found that resveratrol decreased expression of anti-apoptotic proteins like BCL2 and increased expression of pro-apoptotic proteins like BAX in cancer cells. Resveratrol, then, may ultimately prove to have value in cell-cycle or ROS-related disease, including radiation-induced cellular damage. As the skin is usually the first tissue that encounters ionizing radiation, the role of human fibroblasts has also been studied in the context of radioprotection. In a recent study, Bao et al. [33] used human fibroblasts to investigate the role of hemin in the radio adaptive response. In fibroblasts, the activity of heme oxygenase 1 (HO1) was observed to increase with exposure to radiation. When a competitive inhibitor of HO1 was given, this radio adaptive response was observed to decrease [33]. Conversely, when cells were treated with hemin, an inducer of HO1, radiation-related DNA damage decreased by nearly 50% [33]. These results suggest that upregulation of HO1 could improve cell viability after radiation exposure, making hemin a potential candidate for radioprotection [33].

Natural antioxidant - Acteoside

Another substance studied using human fibroblasts is acteoside, a known antioxidant and anti-inflammatory. Acteoside is a phenylethanoid glycoside derived from the Cistanche salsa plant of northwest China. Yang et al. [34]studied the effects of acteoside on irradiated human fibroblasts. Pre-incubation with acteoside decreased the generation of ROS and led to a significant decrease in apoptosis compared to controls. Acteoside was also observed to down-regulate pro-caspase 3, decrease expression of Bax, and increase expression of BCl2 compared to controls [30]. Perhaps most significantly, Yang et al. [34] showed that acteoside leads to a significant increase in the phosphorylation of ERK and JNK, suggesting it could play a role in cell cycle regulation and increase its potential as a radioprotective agent. Pei et al. [10] studied the oxazolone derivative GANRA-5 (a known free radical scavenger) on human lung fibroblasts. Interestingly, in this study GANRA-5 was shown to be radioprotective in a variety of radiation settings (X-ray, carbon ion beams, microwave, UV light). The authors also noted that fibroblasts protected with GANRA-5 had a significantly lower formation of gamma- H2AX foci compared to controls after exposure to X-ray radiation [10]. The potential combination of tolerability and efficacy make GANRA-5 an important radioprotective agent for future studies and, perhaps, clinical use. Wan et al. [35] used antioxidants as radioprotective agents against radiation-induced oxidative stress in human epithelial cells. The antioxidants they studied included NAC, ascorbic acid, sodium ascorbate, alpha-lipoic acid, coenzyme Q10, l-selenomethionine, and vitamin E. In this experiment, Wan et al. [35] exposed human breast epithelial cells to X-ray and gamma-ray radiation. Before radiation exposure, cells were treated with a medium containing a single antioxidant, a combination of antioxidants, or an antioxidant-free control. They found that while individual antioxidants provided varying degrees of protection against X-rays and gamma-ray-induced DNA damage, combinations of several anti-oxidants produced the most profound reduction in DNA damage (94.7% reduction against X-ray radiation and 100% reduction against gamma-ray radiation) [35]. Wan et al. [35] also noted that water-soluble free radical scavengers (such as NAC, ascorbic acid, sodium ascorbate, and α-lipoic acid) were the most effective at reducing DNA damage. They hypothesize that this is because many free radicals are likely generated in an aqueous environment, and water-soluble antioxidants will be present at the source of free radical generation [35]. In contrast to some prior studies [9], Wan et al. [35] emphasized that the combination of antioxidants was more effective than individual antioxidants in protecting against radiation-induced oxidative stress. They expected this result and suggested that can replenish one another and increase the total pool of antioxidants available to react with free radicals [35]. Further studies should be pursued to establish whether additive or synergistic interactions occur among radioprotective antioxidants.

Natural antioxidant - acteoside