The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed.

Hippophae rhamnoides (RH-3), which has been recently reported to elicit dose-dependent pro- and antioxidant properties in vitro, induced apoptosis in murine thymocytes. In a concentration-dependent manner, RH-3 induced apoptosis in thymocytes in ex vivo conditions. The maximum effect was observed with 100 microg/mL of RH-3. Beyond this dose, the induction of apoptosis was inhibited, as seen on the ladder formation. However, apoptotic body formation, another indicator of apoptosis, was not manifested when various doses of RH-3 (20-200 microg/mL) were administered. RH-3 (>100 microg/mL) compacted chromatin in the form of densely stained masses, and subsequent treatment with proteinase-K loosened them and developed a halo around each mass. RH-3 treatment of cells that had already undergone apoptosis induced chromatin compaction, which made the ladder invisible. During in vivo experiments in mice, the radioprotective dose of RH-3 (30 mg/kg b.w.) induced significant DNA fragmentation in thymocytes studied spectrofluorimetrically. RH-3 treatment before irradiation in vivo enhanced radiation-induced apoptosis. These results were confirmed by hypodiploid population studied flow-cytometrically and also by ladder formation. RH-3 treatment was prooxidative in nature because it depleted thiols and enhanced lipids peroxidation after 8 hours of treatment. The paradox between the prooxidant and the antioxidant effects of RH-3 in the context of its overall radioprotective efficacy has been explained.

Hippophae rhamnoides or seabuckthorn is used extensively in Indian and Tibetan traditional medicine for the treatment of circulatory disorders, ischemic heart disease, hepatic injury, and neoplasia. In the present study, we have evaluated the radioprotective potential of REC-1001, a fraction isolated from the berries of H. rhamnoides. Chemical analysis of the extract indicated that REC-1001 was approximately 68% by weight polyphenols, and contained kaempferol, isorhamnetin, and quercetin. The effect of REC-1001 on modulating radiation-induced DNA damage was determined in murine thymocytes by measuring nonspecific nuclear DNA damage at the whole genome level using the alkaline halo assay and by measuring sequence/gene-specific DNA damage both in nuclear DNA (beta-globin gene) and in mitochondrial DNA using a quantitative polymerase chain reaction. Treatment with 10 Gy resulted in a significant amount of DNA damage in the halo assay and reductions in the amplification of both the beta-globin gene and mitochondrial DNA. REC-1001 dose-dependently reduced the amount of damage detected in each assay, with the maximum protective effects observed at the highest REC-1001 dose evaluated (250 micro g/ml). Studies measuring the nicking of naked plasmid DNA further established the radioprotective effect of REC-1001. To elucidate possible mechanisms of action, the antioxidant properties and the free-radical scavenging activities of REC-1001 were evaluated. REC-1001 dose-dependently scavenged radiation-induced hydroxyl radicals, chemically-generated superoxide anions, stabilized DPPH radicals, and reduced Fe(3+) to Fe(2+). The results of the study indicate that the REC-1001 extract of H. rhamnoides protects mitochondrial and genomic DNA from radiation-induced damage. The polyphenols/flavonoids present in the extract might be responsible for the free radical scavenging and DNA protection afforded by REC-1001.

RP-1, a herbal preparation of Podophyllum hexandrum has already been reported to provide protection against whole body lethal gamma irradiation (10 Gy). It has also been reported to render radioprotection to germ cells during spermatogenesis. Present study was undertaken to unravel the cellular and molecular mechanism of action of RP-1 on testicular system in strain 'A' mice. Various antioxidant parameters such as thiol content, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) enzyme activity, lipid peroxidation (LPO) and total protein levels were investigated. Thiol content was seen to increase significantly (p < 0.05) in both RP-1 alone and RP-1 pretreated irradiated groups over the irradiated groups at 8, 16 and 24 h. Irradiation (10 Gy) significantly decreased GPx, GST and GR activity in comparison to untreated control but RP-1 treatment before irradiation significantly (p < 0.05) countered radiation-induced decrease in the activity of these enzymes. Radiation-induced LPO was also found to be reduced at all time intervals by RP-1 treatment before irradiation. As compared to irradiated group the protein content in testicular tissue was increased in RP-1 pretreated irradiated group at 4 and 16 h significantly (p < 0.05). Comets revealed by single-cell gel electrophoresis were significantly longer (p < 0.001) in irradiated mice than in unirradiated control. RP-1 treatment before irradiation, however, rendered significant increase (p < 0.05) in comet length over the corresponding control and irradiated group initially at 4 h but at later time points, this was reduced significantly (p < 0.01) as compared to the irradiated group. RP-1 treatment alone rendered shorter comets at 8, 16 and 24 h than irradiated groups (p < 0.001). This study implies that RP-1 offers radioprotection at biochemical and cytogenetic level by protecting antioxidant enzymes, reducing LPO and increasing thiol content.

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