title: Podophyllum hexandrum (Himalayan mayapple) extract provides radioprotection by modulating the expression of proteins associated with apoptosis.
abstract: Podophyllum hexandrum Royale (Himalayan mayapple), a high-altitude Himalayan plant, has been shown to provide over 80% whole-body radioprotection in mice. To investigate the radioprotective potential of P. hexandrum at the molecular level, expression patterns of various proteins associated with apoptosis were studied in the spleen of male Swiss albino strain A mice by immunoblotting. Treatment with P. hexandrum [200 mg/kg of body weight; an ethanolic 50% (w/v) extract delivered intraperitoneally] 2 h before irradiation resulted in MAPKAP (mitogen-activated protein kinase-activated protein) kinase-2 activation along with HSF-1 (heat-shock transcription factor-1), leading to up-regulation of HSP-70 (heat-shock protein-70) as compared with sham-irradiated (10 Gy) mice. Strong inhibition of AIF (apoptosis-inducing factor) expression was observed in the mice treated with P. hexandrum 2 h before irradiation as compared with the sham-irradiated group. Inhibition in the translocation of free NF-kappaB (nuclear factor kappaB) from cytoplasm to nucleus was observed upon P. hexandrum pretreatment 2 h before irradiation when compared with radiation-treated mice. P. hexandrum pre-treatment (2 h before irradiation) resulted in inhibition of NF-kappaB translocation, and the expression of tumour suppressor protein p53 was observed to be down-regulated as compared with sham-irradiated control. An increase in the expression of proteins responsible for cell proliferation [Bcl-2 (B-cell chronic lymphocytic lymphoma 2), Ras-GAP (Ras-GTPase-activating protein) and PCNA (proliferating cell nuclear antigen)] was observed in the P. hexandrum-pretreated irradiated mice as compared with sham-irradiated controls. Caspase 3 activation resulted PARP [poly(ADP-ribose) DNA polymerase] cleavage, and DNA degradation was strongly inhibited in the mice treated with P. hexandrm (+/-irradiation) as compared with the mice treated with radiation (+/-heat shock). The present study thus clearly demonstrated that P. hexandrum extract provides protection from gamma-radiation by the modulation of expression of proteins associated with cell death.
authors.affiliation: Division of Radiopharmaceuticals and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Brigadier S.K. Mazumdar Road, Delhi-110054, India.
authors.forename: Raj
authors.initials: R
authors.lastname: Kumar
authors.forename: Pankaj Kumar
authors.initials: PK
authors.lastname: Singh
authors.forename: Ashok
authors.initials: A
authors.lastname: Sharma
authors.forename: Jagdish
authors.initials: J
authors.lastname: Prasad
authors.forename: Ravinder
authors.initials: R
authors.lastname: Sagar
authors.forename: Surender
authors.initials: S
authors.lastname: Singh
authors.forename: Rajesh
authors.initials: R
authors.lastname: Arora
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001059:Apoproteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005720:Gamma Rays / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000008:administration & dosage*; D011035:Podophyllum / Q000737:chemistry*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D011835:Radiation Protection / Q000379:methods; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000378:metabolism; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001059:Apoproteins; D016207:Cytokines; D010936:Plant Extracts; D011837:Radiation-Protective Agents