Protection from radiation-induced mitochondrial and genomic DNA damage by an extract of Hippophae rhamnoides.
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.
Shukla
Sandeep Kumar
SK
Division of Radioimaging, Bioinformatics, and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Chaudhary
Pankaj
P
Kumar
Indracanti Prem
IP
Samanta
Namita
N
Afrin
Farhat
F
Gupta
Manju Lata
ML
Sharma
Upendra Kumar
UK
Sinha
Arun Kumar
AK
Sharma
Yogendra Kumar
YK
Sharma
Rakesh Kumar
RK
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000528:radiation effects; D044948:Flavonols / Q000032:analysis; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005720:Gamma Rays / Q000009:adverse effects*; D031281:Hippophae / Q000737:chemistry*; D006834:Hydrazines / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D066298:In Vitro Techniques; D044949:Kaempferols / Q000032:analysis; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D010636:Phenols / Q000032:analysis; D010851:Picrates; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011794:Quercetin / Q000032:analysis / Q000031:analogs & derivatives; D013481:Superoxides / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
D001713:Biphenyl Compounds; D004272:DNA, Mitochondrial; D044948:Flavonols; D016166:Free Radical Scavengers; D006834:Hydrazines; D044949:Kaempferols; D010636:Phenols; D010851:Picrates; D010936:Plant Extracts; C047368:3-methylquercetin; D013481:Superoxides; D017665:Hydroxyl Radical; C006552:kaempferol; D004247:DNA; D011794:Quercetin; C004931:1,1-diphenyl-2-picrylhydrazyl