Evaluation of radioprotective activities Rhodiola imbricata Edgew--a high altitude plant.
The present study reports the radioprotective properties of a hydro-alcoholic rhizome extract of Rhodiola imbricata (code named REC-7004), a plant native to the high-altitude Himalayas. The radioprotective effect, along with its relevant superoxide ion scavenging, metal chelation, antioxidant, anti-lipid peroxidation and anti-hemolytic activities was evaluated under both in vitro and in vivo conditions. Chemical analysis showed the presence of high content of polyphenolics (0.971 +/- 0.01 mg% of quercetin). Absorption spectra analysis revealed constituents that absorb in the range of 220-290 nm, while high-performance liquid chromatography (HPLC) analysis confirmed the presence of four major peaks with retention times of 4.780, 5.767, 6.397 and 7.577 min. REC-7004 was found to lower lipid oxidation significantly (p < 0.05) at concentrations viz., 8 and 80 microg/ml respectively as compared to reduced glutathione, although the optimally protective dose was 80 microg/ml, which showed 59.5% inhibition of induction of linoleic acid degradation within first 24 h. The metal chelation activity of REC-7004 was found to increase concomitantly from 1 to 50 microg/ml. REC-7004 (10-50 microg/ml) exhibited significant metal chelation activity (p < 0.05), as compared to control, and maximum percentage inhibition (30%) of formation of iron-2,2'-bi-pyridyl complex was observed at 50 microg/ml, which correlated well with quercetin (34.9%), taken as standard. The reducing power of REC-7004 increased in a dose-dependent manner. The absorption unit value of REC-7004 was significantly lower (0.0183 +/- 0.0033) as compared to butylated hydroxy toluene, a standard antioxidant (0.230 +/- 0.091), confirming its high reducing ability. Superoxide ion scavenging ability of REC-7004 exhibited a dose-dependent increase (1-100 microg/ml) and was significantly higher (p < 0.05) than that of quercetin at lower concentrations (1-10 microg/ml), while at 100 microg/ml, both quercetin and REC-7004 scavenged over 90% superoxide anions. MTT assay in U87 cell line revealed an increase in percent survival of cells at doses between 25 and 125 microg/ml in case of drug + radiation group. In vivo evaluation of radio-protective efficacy in mice revealed that intraperitoneal administration of REC-7004 (maximally effective dose: 400 mg/kg b.w.) 30 min prior to lethal (10 Gy) total-body gamma-irradiation rendered 83.3% survival. The ability of REC-7004 to inhibit lipid peroxidation induced by iron/ascorbate, radiation (250 Gy) and their combination [i.e., iron/ascorbate and radiation (250 Gy)], was also investigated and was found to decrease in a dose-dependent manner (0.05-2 mg/ml). The maximum percent inhibition of formation of MDA-TBA complex at 2 mg/ml in case of iron/ascorbate, radiation (250 Gy) and both i.e., iron/ascorbate with radiation (250 Gy) was 53.78, 63.07, and 51.76% respectively and were found to be comparable to that of quercetin. REC-7004 (1 microg/ml) also exhibited significant anti-hemolytic capacity by preventing radiation-induced membrane degeneration of human erythrocytes. In conclusion, Rhodiola renders in vitro and in vivo radioprotection via multifarious mechanisms that act in a synergistic manner.
Arora
Rajesh
R
Division of Radiopharmaceuticals and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Chawla
Raman
R
Sagar
Ravinder
R
Prasad
Jagdish
J
Singh
Surendar
S
Kumar
Raj
R
Sharma
Ashok
A
Singh
Shikha
S
Sharma
Rakesh Kumar
RK
D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005720:Gamma Rays; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D029771:Rhodiola / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D003037:Cobalt Radioisotopes; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D010936:Plant Extracts; D011837:Radiation-Protective Agents