title: Radioprotective and antioxidant properties of low-altitude Podophyllum hexandrum (LAPH).
abstract: The development of nontoxic yet effective radioprotectors is needed because of the increasing risk of human exposure to ionizing radiation. We have reported that high-altitude Podophyllum hexandrum (HAPH) confers a radioprotective effect in in vitro and in vivo models. The present study reports on the antioxidant and radioprotective properties of low-altitude Podophyllum hexandrum (LAPH), from which the toxic compound podophyllotoxin has been partially removed during the extraction process. Using HPLC,we estimated the relative content of two marker compounds, podophyllotoxin and podophyllotoxin glycoside, in low-altitude Podophyllum extract (LAPE) and found them to be 23.3% and 9.50%, respectively. The ferrous ion chelation potential of LAPE was estimated using the 2,2 bipyridyl assay, and the activity was found to be increased concomitantly with the increase in its concentration, with a maximal inhibition at 25 microg/mL (42.20%) as compared to quercetin (34.9%). The electron donation potential of LAPE was also evaluated, because the antioxidant activities of natural products are known to bear a direct correlation with their ability to donate electrons. The concentration required to attain unit absorbance values at 700 nm were 0.230541+/-0.09 and 0.041+/-0.06 for butylated hydroxyl toluene and LAPE, respectively, indicating a higher antioxidant activity of LAPE. The free radical scavenging ability of LAPE was also assessed and exhibited a dose-dependant increase (1-100 microg/mL), comparable to that of quercetin at 25 microg/mL. The role of LAPE in protecting DNA was evaluated, and it was found that LAPE (30 microg/mL) rendered its maximum radioprotection against the 250 Gy-induced damage in the plasmid (pBR322) relaxation assay. LAPE significantly inhibited radiation-induced, iron/ascorbate- and combined stress (iron/ascorbate and radiation)-induced formation of TBARS (p<0.05). We conclude that LAPH, with its easy accessibility, ease of cultivation, multifarious radioprotective properties, and role as a renewable source of bioactive constituents, along with its low associated toxicity (due to partial removal of podophyllotoxin), enhances its possible use for human clinical applications.
authors.affiliation: Division of Radiopharmaceuticals and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Arora
authors.forename: Raman
authors.initials: R
authors.lastname: Chawla
authors.forename: Satish Chander
authors.initials: SC
authors.lastname: Puri
authors.forename: Ravinder
authors.initials: R
authors.lastname: Sagar
authors.forename: Shikha
authors.initials: S
authors.lastname: Singh
authors.forename: Raj
authors.initials: R
authors.lastname: Kumar
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Jagdish
authors.initials: J
authors.lastname: Prasad
authors.forename: Surender
authors.initials: S
authors.lastname: Singh
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Kaur
authors.forename: Pankaj
authors.initials: P
authors.lastname: Chaudhary
authors.forename: Ghulam Nabi
authors.initials: GN
authors.lastname: Qazi
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000531:Altitude; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004583:Electrons; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005720:Gamma Rays; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000528:radiation effects; D008099:Liver / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011034:Podophyllotoxin / Q000032:analysis / Q000494:pharmacology; D011035:Podophyllum / Q000737:chemistry; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D010936:Plant Extracts; D011837:Radiation-Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; D011034:Podophyllotoxin