Plant Extracts and Plant-Derived Compounds: Promising Players in Countermeasure Strategy Against Radiological Exposure: A Review

Radiation exposure leads to several pathophysiological conditions, including oxidative damage, inflammation and fibrosis, thereby affecting the survival of organisms. This review explores the radiation countermeasure properties of fourteen (14) plant extracts or plant-derived compounds against these cellular manifestations. It was aimed at evaluating the possible role of plants or its constituents in radiation countermeasure strategy. All the 14 plant extracts or compounds derived from it and considered in this review have shown some radioprotection in different in vivo, ex vivo and or in vitro models of radiological injury. However, few have demonstrated advantages over the others. C. majus possessing antioxidant, anti-inflammatory and immunomodulatory effects appears to be promising in radioprotection. Its crude extracts as well as various alkaloids and flavonoids derived from it, have shown to enhance survival rate in irradiated mice. Similarly, curcumin with its antioxidant and the ability to ameliorate late effect of radiation exposure, combined with improvement in survival in experimental animal following irradiation, makes it another probable candidate against radiological injury. Furthermore, the extracts of P. hexandrum and P. kurroa in combine treatment regime, M. piperita, E. officinalis, A. sinensis, nutmeg, genistein and ginsan warrants further studies on their radioprotective potentials. However, one that has received a lot of attention is the dietary flaxseed. The scavenging ability against radiation-induced free radicals, prevention of radiation-induced lipid peroxidation, reduction in radiation cachexia, level of inflammatory cytokines and fibrosis, are some of the remarkable characteristics of flaxseed in animal models of radiation injury. While countering the harmful effects of radiation exposure, it has shown its ability to enhance survival rate in experimental animals. Further, flaxseed has been tested and found to be equally effective when administered before or after irradiation, and against low doses (less than or equal to5 Gy) to the whole body or high doses (12 to 13.5 Gy) to the whole thorax. This is particularly relevant since apart from the possibility of using it in pre-conditioning regime in radiotherapy, it could also be used during nuclear plant leakage/accidents and radiological terrorism, which are not pre-determined scenarios. However, considering the infancy of the field of plant-based radioprotectors, all the above-mentioned plant extracts/plant-derived compounds deserves further stringent study in different models of radiation injury. (Authors abstract)

The concern of radiation hazards increases with the use of more and more radiation clinically, particularly, as a treatment regime for different types of cancers. Radiation, particularly the ionizing radiation (IR), has been known to cause different types of effects in biological systems ranging from oxidative damages caused by ionization products, free radicals, and reactive oxygen species (ROS) to damages to DNA and its interaction with macromolecules such as proteins.  Radiation induced inflammation is an important side effect that contributes to normal tissue injury. The initial phase of radiation induced injury is marked by the increase in the synthesis of pro inflammatory cytokines. A number of chemical agents showed mitigation to radiation induced injuries in animal models. Among chemical radioprotectors (thiols, aminothiols, thiadiazoles, benzothiazoles, etc) that has been tested clinically, the efficacy is limited by high toxicity and unwanted side effects associated with them.  Therefore, the focus has been shifted to the evaluation of the radioprotective potential of plants and herbs, and compounds derived from them. This review attempts to evaluate the roles of fourteen (14) plant extracts or plant-derived compounds in mitigation of radiological effects. Although, radioprotection by these plants has been evaluated by looking at the modulation of different cellular/molecular events, the emphasis has been laid on their antioxidant, anti-inflammation and anti-fibrotic potential, and on survival in animal models. This review evaluates the radioprotective effects based on studies on these cellular aspects carried out to test the radioprotective potential.

Linum usitatissimum L. (flaxseed, FS) has been reported to exhibit antitumor, free radical scavenging ability and prevention against oxidative tissue damages when administered prior to radiation exposure. Antioxidant action of FS was evaluated in PMVEC, isolated from murine lungs. It was grown to confluence on culture dishes and treated with increasing concentrations of secoisolariciresinol diglucoside (SDG), isolated from FS. Cultures were then exposed to 2 Gy of IR (Dose rate of 1.14 Gy/min). It was found that a significant increase in ROS generation occurred shortly after radiation (assess by fluorescent imaging), which was diminished in a dose dependent manner by SDG. In the same study, it was demonstrated that mice fed with 10 percent FS as dietary supplementation, 3 weeks before irradiation (a single fraction of 13.5 Gy of X radiation to the whole thorax) could mitigate oxidative lung injury. In this case, it was further revealed by BALF analysis that white blood cell (WBC) influx and lipid peroxidation was significantly reduced in irradiated FS fed mice as compared to irradiated mice fed with control diet. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of markers of lung injury such as Bax, p21 and TGF-β1 expression levels at 24 h post thoracic irradiation have shown that 10percent FS-fed irradiated mice had significantly reduced expression of Bax, p21 and TGF beta 1 compared to control diet fed irradiated mice. These observations were very significant since these biomarkers show strong correlation with the severity of radiation-induced lung injury in different experimental models. Analysis of hematoxylin and eosin (H and E) stained lung sections from all animals that survived the 4 month long-term experiments demonstrated that IR induced influx of alveolar neutrophils (PMN) and macrophages (MF) were significantly reduced by 10 percent FS compared to mice fed with control diet. Moreover, at 4 month post irradiation, the trichrome staining of lung tissue showed reduction in the degree of radiation fibrosis and structural damage in 10 percent FS treated group in comparison to control diet-fed irradiated mice. The histopathological changes were scored as radiation fibrotic index (FI) and it indicated significant decrease in lung fibrosis in irradiated lungs from 10 percent FS vs 0 percent FS fed irradiated mice. The fibrotic changes were supported by the hydroxyproline (OH proline) assay result, which showed significantly decreased lung OH proline content four months after IR exposure as compared to irradiated mice fed control diet.  FS with its potent effect against radiological challenge in ex vivo as well as animal models, could be an ideal candidate for countermeasure strategy against radiation. Apart from the beneficial counter radiation effects, that include antioxidant, anti inflammation, anti fibrosis and enhancement of survival in experimental animals, it was effective when administered before or after irradiation.
Based on current information available on the plant extracts and plant derived compounds considered in this article, one that has the advantage over all the others is flaxseed. The scavenging ability against radiation-induced free radicals, prevention of radiation induced lipid peroxidation, reduction in radiation cachexia, level of inflammatory cytokines and fibrosis, are some of the characteristics of flaxseed in animal models of radiation injury. While countering the harmful effects of radiation exposure, it has shown its ability to enhance survival rate in experimental animals. Further, flaxseed has been tested and found to be equally effective when administered before or after irradiation, and against low doses to the whole body or high doses to the whole thorax. This is particularly relevant since apart from the possibility of using it in pre conditioning regime in radiotherapy, it could also be used during nuclear plant leakage or accidents and radiological terrorism, which are not pre-determined scenarios. (Editors comments)