title: Podophyllum hexandrum as a potential botanical supplement for the medical management of nuclear and radiological emergencies (NREs) and free radical-mediated ailments: leads from in vitro/in vivo radioprotective efficacy evaluation.
abstract: Management of radiation-induced reactive oxygen/nitrogen species requires a holistic approach to mitigate the deleterious effects of free radicals. Flora of the Himalayas, which prevails under extreme climatic conditions, has been explored for its potential utility to develop radioprotective drugs. The Himalayan high altitude medicinal plant, Podophyllum hexandrum Royle, was selected on the basis of its unique properties, and a novel fractionated nonpolar extract (REC-2003) was prepared and evaluated for radioprotective efficacy, in vitro as well as in vivo. The free radical scavenging activity of REC-2003 was found to be > 75% (20 μg/ml) with maximum superoxide scavenging activity (57.56 ± 1.38%) recorded at 1 mg/ml concentration (tetrazolium-based estimation). More than 30% inhibition of nitric oxide radicals was observed at concentrations > 0.5 mg/ml, while hydroxyl radical scavenging activity (deoxy-D-ribose assay) exhibited a dose-dependent (100-600 μg/ml) increase. Significantly high (90%) protection to human erythrocytes was observed at 75 μg/ml, which was found to be the most optimized dose. Similarly, more than 90% inhibition was observed against lipid peroxidation (evaluated by estimating levels of malondialdehyde). The significant antihemolytic potential of REC-2003 could be attributed to its ability to scavenge free radicals, reduce peroxidative stress on lipid membranes, and render protection to DNA (evaluated using plasmid relaxation assay). All these activities holistically contributed toward the radioprotective ability. REC-2003 (8 mg/kg BW; intraperitoneal (i.p.), -30 min) rendered > 80% total-body protection in Swiss Albino Strain 'A' mice [against lethal radiation (10 Gy)] in a 30-day survival assay. Phytochemical characterization of the constituents of REC-2003 revealed the presence of polyphenolics (flavonoids). The characterized constituents also included the aryl-tetralin lignans like podophyllotoxin, its glycoside, 4'-demethyl derivative, and epi-podophyllotoxin. The optimized requisite single dose (8 mg/KgBW; i.p., -30 min) for obtaining significant radioprotection is reasonably low and establishes its future utility as a dietary supplement in the medical management of free radical-mediated diseases and specifically for rescue missions during nuclear and radiological emergencies (NREs).
authors.affiliation: Radiation Biotechnology Group, Institute of Nuclear Medicine and Allied Sciences (INMAS), Defense Research and Development Organization (DRDO), Brig. SK Mazumdar Road, Delhi-110054, India. rajesharoradr@rediffmail.com
authors.forename: Rajesh
authors.initials: R
authors.lastname: Arora
authors.forename: Raman
authors.initials: R
authors.lastname: Chawla
authors.forename: Atlar Singh
authors.initials: AS
authors.lastname: Dhaker
authors.forename: Manish
authors.initials: M
authors.lastname: Adhikari
authors.forename: Jyoti
authors.initials: J
authors.lastname: Sharma
authors.forename: Shikha
authors.initials: S
authors.lastname: Singh
authors.forename: Damodar
authors.initials: D
authors.lastname: Gupta
authors.forename: Raj
authors.initials: R
authors.lastname: Kumar
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Sharma
authors.forename: Rajender P
authors.initials: RP
authors.lastname: Tripathi
mesh_terms: D000818:Animals; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D019587:Dietary Supplements; D004630:Emergencies; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D005419:Flavonoids / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D005720:Gamma Rays; D006801:Humans; D017705:Lignans / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D011035:Podophyllum / Q000737:chemistry*; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D018788:Radioactive Hazard Release; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D005419:Flavonoids; D016166:Free Radical Scavengers; D005609:Free Radicals; D017705:Lignans; D010936:Plant Extracts; D011837:Radiation-Protective Agents; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D004247:DNA