The combination of the active principles of Podophyllum hexandrum supports early recovery of the gastrointestinal system via activation of Nrf2-HO-1 signaling and the hematopoietic system, leading to effective whole-body survival in lethally irradiated mice

References

• Hosseinimehr SJ. Trends in the development of radioprotective agents. Drug Discov Today 2007;12:794–805.
   PubMed Web of Science ®Google Scholar
• Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: the first selective-target and broad-spectrum radioprotector. Oncologist 2007;12:738–747.
   PubMed Web of Science ®Google Scholar
• Riley PA. Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol 1994;65: 27–33.
   PubMed Web of Science ®Google Scholar
• Holahan, EV Jr. Cellular radiation biology. In: Conklin JJ, Walker RI (eds.). Military Radiobiology. London: Academic Press; 1987. pp. 87–110.
   Google Scholar
• Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 2007;47:89–116.
   PubMed Web of Science ®Google Scholar
• Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol Today 1994;15:7–10.
   PubMedGoogle Scholar
• Carmody RJ, Cotter TG. Signalling apoptosis: a radical approach. Redox Rep 2001;6:77–90.
   PubMed Web of Science ®Google Scholar
• Cragg GM, Newman DJ, Snader KM. Natural products in drug discovery and development. J Nat Prod 1997;60:52–60.
   PubMed Web of Science ®Google Scholar
• Sagar RK, Chawla R, Arora R, Singh S, Krishna B, Sharma RK, et al. Protection of the hematopoietic system by Podophyllum hexandrum against gamma radiation-induced damage. Plant Med 2006;72:114–120.
   PubMedGoogle Scholar
• Gupta ML, Sankhwar S, Verma S, Devi M, Samanta N, Agrawala PK, et al. Whole body protection to lethally irradiated mice by oral administration of semipurified fraction of Podophyllum hexandrum and post irradiation treatment of Picrorhiza kurroa. Tokai J Exp Clin Med 2008;33:6–12.
   PubMedGoogle Scholar
• Lata M, Prasad J, Singh S, Kumar R, Singh L, Chaudhary P, et al. Whole body protection against lethal ionizing radiation in mice by REC-2001: a semi-purified fraction of Podophyllum hexandrum. Phytomedicine 2009;16: 47–55.
   PubMed Web of Science ®Google Scholar
• Gupta ML, Gupta V, Shukla SK, Verma S, Sankhwar S, Dutta A, Suri KA. Inhibition in radiation mediated cellular toxicity by minimizing free radical flux: One of the possible mechanisms of biological protection against lethal ionizing radiation by a sub-fraction of Podophyllum hexandrum. Cell Mol Biol 2010;11:56:OL1341–OL1349.
   Google Scholar
• Sankhwar S, Gupta ML, Gupta V, Verma S, Suri KA, Devi M, et al. Podophyllum hexandrum-mediated survival protection and restoration of other cellular injuries in lethally irradiated mice. Evid Based Complement Alternat Med 2011;175140. doi: 10.1093/ecam/nep061.
   Google Scholar
• Dutta A, Verma S, Sankhwar S, Flora SJS, Gupta ML. Bioavailability, antioxidant and non toxic properties of a radioprotective formulation prepared from isolated compounds of Podophyllum hexandrum: A study in mouse model. Cell Mol Biol 2012;58:OL1646–OL1653.
   PubMedGoogle Scholar
• Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978;52:302–310.
   PubMedGoogle Scholar
• Hissin PJ, Hilf R. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 1976;74:214–226.
   PubMed Web of Science ®Google Scholar
• Carlberg I, Mannervik B. Glutathione Reductase. Methods Enzymol 1985;113:484–490.
   PubMed Web of Science ®Google Scholar
• Egan LJ, Eckmann L, Greten FR, Chae S, Li ZW, Myhre GM, et al. IkappaB-kinase beta-dependent NF-kappaB activation provides radioprotection to the intestinal epithelium. Proc Natl Acad Sci USA 2004;101:2452–2457.
   PubMed Web of Science ®Google Scholar
• Perharic L, Shaw D, Colbridge M, House I, Leon C, Murray V. Toxicological problems resulting from exposure to traditional remedies and food supplements. Drug Saf 1994; 11:284–294.
   PubMed Web of Science ®Google Scholar
• Drew K, Myers SP. Safety issues in herbal medicine: implications for the health professions. Med J Aust 1997;166:538–541.
   PubMed Web of Science ®Google Scholar
• Gupta ML, Sankhwar S, Verma S, Samanta N, Gupta V, Rajkumar. A radioprotective formulation. Indian Patent Application No. 154/DEL/28 Jan 2009.
   Google Scholar
• Devi PU, Bisht KS, Vinitha M. A comparative study of radioprotection by Ocimum flavonoids and synthetic aminothiol protectors in the mouse. Brit J Radiol 1998;71:782–784.
   PubMed Web of Science ®Google Scholar
• Van Bekkum DW. Radiation sensitivity of hemopoietic stem cell. Radiat Res 1991;128:S4–8.
   PubMed Web of Science ®Google Scholar
• Griffith JQ Jr, Couch JF. Inhibition by rutin of capillary injury by alpha-radiation in rats. Blood 1951;6:552–554.
   PubMedGoogle Scholar
• Gunter-Smith PJ. Effect of ionizing radiation on gastrointestinal physiology. In: Conklin JJ, Walker RI (eds.). Military Radiobiology. London: Academic Press; 1987. pp. 135–151.
   Google Scholar
• Narayana RK, Sripal Reddy MS, Chaluvadi MR, Krishna DR. Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential. Ind J Pharmacol 2001;33: 2–16.
   Google Scholar
• Meister A, Anderson ME. Glutathione. Annu Rev Biochem 1983;52:711–760.
   PubMed Web of Science ®Google Scholar
• Circu ML, Aw TY. Redox biology of the intestine. Free Radic Res 2011;45:1245–1266.
   PubMed Web of Science ®Google Scholar
• Wilhelm J. Metabolic aspects of membrane lipid peroxidation. Acta Univ Carol Med Monogr 1990;137:1–53.
   PubMedGoogle Scholar
• Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 1997;272:20313–20316.
   PubMed Web of Science ®Google Scholar
• Saini R, Verma S, Singh A, Gupta ML. Role of active principles of Podophyllum hexandrum in amelioration of radiation mediated lung injuries by reactive oxygen/nitrogen species reduction. Cell Bio 2013;2:105–116.
   Google Scholar
• Verma S, Kalita B, Saini R, Gupta ML. The protective effect of active principles of Podophyllum hexandrum on hepato-pulmonary toxicity induced in irradiated mice. Oxi Antioxi Med Sci 2014;3:51–64.
   Google Scholar
• Srivastava NN, Shukla SK, Yashavarddhan MH, Devi M, Tripathi RP, Gupta ML. Modification of radiation–induced DNA double strand break repair pathways by chemicals extracted from Podophyllum hexandrum: An in-vitro study in human blood lymphocytes. Environ Mol Mutagen 2014;55:436–448.
   PubMed Web of Science ®Google Scholar
• Dutta S, Gupta ML. Alleviation of radiation induced genomic damage in human peripheral blood lymphocytes by active principles of Podophyllum hexandrum: an in vitro study using chromosomal and CBMN assay. Mutagenesis 2014;29: 139–147.
   PubMed Web of Science ®Google Scholar
• Rios JL, Giner RM, Prieto JM. New findings on the bioactivity of lignans. Stud Nat Prod 2002;26:183–292.
   Google Scholar
• Guerrane M, Jiang ZZ, Zhang LY. Podophyllotoxin, a medicinal agent of plant origin: past, present and future. Chinese J Nat Med 2012;10:161–169.
   Google Scholar
• Stahelin H, Von Wartburg A. From podophyllotoxin glucoside to etoposide. Prog Drug Res 1989;33:169–267.
   PubMedGoogle Scholar
• Robak J, Glyglewski RJ. Flavonoids are scavengers of superoxide anions. Biochem Pharmacol 1988;37: 837–841.
   PubMed Web of Science ®Google Scholar
• SR Husain, Cillard J, Cillard P. Hydroxy radical scavenging activity of flavonoids. Phytochemistry 1987;26:2489–2492.
   Web of Science ®Google Scholar
• Ratty AK, Das NP. Effects of flavonoids on nonenzymatic lipid peroxidation: structure-activity relationship. Biochem Med Metabol Biol 1988;39:67–79.
   Google Scholar
• Patil SL, Mallaiah SH, Patil RK. Antioxidative and radioprotective potential of rutin and quercetin in Swiss albino mice exposed to gamma radiation. J Med Phys 2013;38:87–92.
   PubMedGoogle Scholar