Protection from radiation-induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides

• Published in: Environmental and molecular mutagenesis 2006-12, Vol.47 (9), p.647-656
• Main Authors: Shukla, Sandeep Kumar, Chaudhary, Pankaj, Kumar, Indracanti Prem, Samanta, Namita, Afrin, Farhat, Gupta, Manju Lata, Sharma, Upendra Kumar, Sinha, Arun Kumar, Sharma, Yogendra Kumar, Sharma, Rakesh Kumar
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biphenyl Compounds - metabolism; DNA - radiation effects; DNA damage; DNA Damage - drug effects; DNA, Mitochondrial - radiation effects; flavonoid; Flavonols - analysis; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; Gamma Rays - adverse effects; Genetics of eukaryotes. Biological and molecular evolution; Hippophae - chemistry; Hippophae rhamnoides; Hydrazines - metabolism; Hydroxyl Radical - metabolism; In Vitro Techniques; Kaempferols - analysis; Male; Medical sciences; Mice; Oxidation-Reduction; Phenols - analysis; Picrates; Plant Extracts - chemistry; Plant Extracts - pharmacology; QPCR; Quercetin - analysis; radioprotection; Superoxides - metabolism; Thymus Gland - cytology; Toxicology
• ISSN: 0893-6692; 1098-2280
• DOI: 10.1002/em.20251

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 ∼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 (β‐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 β‐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 μg/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 Fe3+ to Fe2+. 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. © 2006 Wiley‐Liss, Inc.