Protection of the Hemopoietic System byPodophyllum hexandrumagainst Gamma Radiation-Induced Damage

Abstract

A semi-purified extract of low-altitude Podophyllum hexandrum (REC-2001) containing a relatively low content of podophyllotoxin (3.25 %) exhibited potent antioxidant ability in lipid media (at 1000 microg/mLagainst 0.25 kGy) and significant (p < 0.05) hydroxyl ion scavenging potential (78.83 % at 500 microg/mL). In vitro investigations revealed the ability of REC-2001 to significantly (p < 0.05) reduce radiation-induced hemolysis (2 microg/mL; 46.184 %) and nitric oxide scavenging levels (IC (50): 792 +/- 1.25 microg/mL). Protection of the hemopoietic system of Strain 'A' mice administered 20 mg/kg BW REC-2001 30 min prior to lethal irradiation (10 Gy) was recorded and was mediated by free radical scavenging and lowering of lipid oxidation. Further studies investigating the effects of REC-2001 on stem cell modulation are warranted.

Podophyllum hexandrum Fraction (REC-2006) Shows Higher Radioprotective Efficacy in the p53-Carrying Hepatoma Cell Line: A Role of Cell Cycle Regulatory Proteins

“…25 However, recently, the radioprotective properties of P hexandrum have been discovered and established in our institute. [14][15][16][17][18][19][20][21][22][23][24] In the present study, a phytochemically characterized fraction of P hexandrum (REC-2006), containing podophyllotoxin and its derivatives (4′-demethyl podophyllotoxin-b-D glucopyranoside etc) 19 was used to evaluate the radioprotective efficacy in hepatoma cell lines having different p53 status. Observations of the present study indicated that the cytotoxic and proliferative effect of REC-2006 is independent of the p53 status of the cell lines as both p53-positive and p53-negative cell lines exhibit the median lethal concentration (LC Varied concentration ranges (10 -3 to 10 -7 mg/mL) of REC-2006 and treatment times (0.5, 1, 1.5, 2, and 2.5 h) were used to achieve maximum radioprotective efficacy in both the cell lines.…”

“…Our findings show that REC-2006 renders significant (P < .05) protection in the wild type functional p53 carrying cell line as compared with the p53 null cell line when administered 2 h before exposure to acute IR. Even though the radioprotective properties of P hexandrum were investigated earlier and established in our institute, [14][15][16][17][18][19][20][21][22][23][24] the present observations further open the window for use of REC-2006 as a radioprotector during planned radiation exposures (rescue operation as well as in radiotherapy of tumor cells) because it is well known that more than 60% of the tumor has cells with mutated/nonfunctional p53 protein, which is otherwise required for regulation of downstream genes responsible for cell cycle regulation and DNA repair. Our results indicate a potential for differential radioprotection of p53-expressing cells and p53-deficient cells, particularly during radiotherapy.…”

Stress-Mediated Adaptive Response Leading to Genetic Diversity and Instability in Metabolite Contents of High Medicinal Value: An Overview onPodophyllum hexandrum

“…Due to high proliferation activity this system is known as the most sensitive one to the radiation. Protection to hematopoietic system of mice exposed to whole-body lethal irradiation has also been shown by semipurified extracts of P. hexandrum (Sagar et al, 2006, Sankhwar et al, 2009. Studies have shown upto 90% decline in total blood cell counts within the first few days of radiation in lethally exposed mice.…”

“…Initial studies using whole and semipurified extract of P. hexandrum have exhibited its various properties like free radical scavenging, metal chelation, and modulation of endogenous antioxidant enzymes level (Gupta et al, 2008Lata et al, 2009;Mittal et al, 2001;Sagar et al, 2006;Sankhwar et al, 2009). The ability of P. hexandrum formulations to donate hydrogen atoms (chain-breaking antioxidants) and chelate transition metal ions (secondary antioxidants) has been attributed mainly to the presence of polyphenolic components.…”

Radioprotective Nature of Podophyllum hexandrum (Himalayan Mayapple)

“…P. hexandrum exhibited potent antioxidant ability and significant free radical scavenging potential. It reduced the radiation induced lipid peroxidation [7]. We first reported that P. hexandrum activates heat shock transcription factor-1 (HSF-1) and MAPKAP (mitogen-activated protein kinaseactivated protein) kinase-2 leading to activation of Heat shock protein (HSP) -70 in gastrointestinal murine model [8].…”