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-...

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Veröffentlicht in:Molecular and cellular biochemistry 2005-05, Vol.273 (1-2), p.209-223
Hauptverfasser: Arora, Rajesh, Chawla, Raman, Sagar, Ravinder, Prasad, Jagdish, Singh, Surendar, Kumar, Raj, Sharma, Ashok, Singh, Shikha, Sharma, Rakesh Kumar
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container_end_page 223
container_issue 1-2
container_start_page 209
container_title Molecular and cellular biochemistry
container_volume 273
creator Arora, Rajesh
Chawla, Raman
Sagar, Ravinder
Prasad, Jagdish
Singh, Surendar
Kumar, Raj
Sharma, Ashok
Singh, Shikha
Sharma, Rakesh Kumar
description 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/ascor
doi_str_mv 10.1007/s11010-005-0822-4
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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 &lt; 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 &lt; 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 &lt; 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.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-005-0822-4</identifier><identifier>PMID: 16013456</identifier><language>eng</language><publisher>Netherlands: Springer Nature B.V</publisher><subject>Absorption ; Adult ; Altitude ; Animals ; Anions ; Antioxidants ; Antioxidants - pharmacology ; Aquatic plants ; Cell Proliferation - drug effects ; Cell Proliferation - radiation effects ; Chelation ; Chemical analysis ; Cobalt Radioisotopes ; Erythrocytes - drug effects ; Erythrocytes - radiation effects ; Free Radical Scavengers - pharmacology ; Gamma Rays ; Glioma - metabolism ; Glioma - pathology ; Hemolysis - drug effects ; Hemolysis - radiation effects ; Humans ; Iron ; Iron Chelating Agents - pharmacology ; Irradiation ; Lipid Peroxidation - drug effects ; Lipid Peroxidation - radiation effects ; Lipids ; Liquid chromatography ; Male ; Mice ; Mice, Inbred A ; Oxidative Stress ; Peroxidation ; Plant Extracts - pharmacology ; Plants, Medicinal ; Radiation-Protective Agents - pharmacology ; Rhodiola - chemistry ; Rodents ; Toluene ; Tumor Cells, Cultured</subject><ispartof>Molecular and cellular biochemistry, 2005-05, Vol.273 (1-2), p.209-223</ispartof><rights>Springer Science + Business Media, Inc. 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c326t-b7c623d1efce7bec2d0f89427a2c9fa5cfd5cdca5b25cbc98356dcba69d3da093</citedby><cites>FETCH-LOGICAL-c326t-b7c623d1efce7bec2d0f89427a2c9fa5cfd5cdca5b25cbc98356dcba69d3da093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16013456$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arora, Rajesh</creatorcontrib><creatorcontrib>Chawla, Raman</creatorcontrib><creatorcontrib>Sagar, Ravinder</creatorcontrib><creatorcontrib>Prasad, Jagdish</creatorcontrib><creatorcontrib>Singh, Surendar</creatorcontrib><creatorcontrib>Kumar, Raj</creatorcontrib><creatorcontrib>Sharma, Ashok</creatorcontrib><creatorcontrib>Singh, Shikha</creatorcontrib><creatorcontrib>Sharma, Rakesh Kumar</creatorcontrib><title>Evaluation of radioprotective activities Rhodiola imbricata Edgew--a high altitude plant</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><description>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 &lt; 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 &lt; 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 &lt; 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.</description><subject>Absorption</subject><subject>Adult</subject><subject>Altitude</subject><subject>Animals</subject><subject>Anions</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>Aquatic plants</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Proliferation - radiation effects</subject><subject>Chelation</subject><subject>Chemical analysis</subject><subject>Cobalt Radioisotopes</subject><subject>Erythrocytes - drug effects</subject><subject>Erythrocytes - radiation effects</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Gamma Rays</subject><subject>Glioma - metabolism</subject><subject>Glioma - pathology</subject><subject>Hemolysis - drug effects</subject><subject>Hemolysis - radiation effects</subject><subject>Humans</subject><subject>Iron</subject><subject>Iron Chelating Agents - pharmacology</subject><subject>Irradiation</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Lipid Peroxidation - radiation effects</subject><subject>Lipids</subject><subject>Liquid chromatography</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred A</subject><subject>Oxidative Stress</subject><subject>Peroxidation</subject><subject>Plant Extracts - pharmacology</subject><subject>Plants, Medicinal</subject><subject>Radiation-Protective Agents - pharmacology</subject><subject>Rhodiola - chemistry</subject><subject>Rodents</subject><subject>Toluene</subject><subject>Tumor Cells, Cultured</subject><issn>0300-8177</issn><issn>1573-4919</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkEtLAzEUhYMoWh8_wI0EF-6i9yaTeSxF6gMEQRTchTtJxkamnTrJVPz3Tm1BcHUX9zuHw8fYKcIlAhRXEREQBIAWUEopsh02QV0okVVY7bIJKABRYlEcsMMYP2CEAXGfHWAOqDKdT9jbdEXtQCl0C941vCcXumXfJW9TWHlO6xNS8JE_z7rx1xIP87oPlhLxqXv3X0IQn4X3Gac2hTQ4z5ctLdIx22uojf5ke4_Y6-305eZePD7dPdxcPwqrZJ5EXdhcKoe-sb6ovZUOmrLKZEHSVg1p2zhtnSVdS21rW5VK587WlFdOOYJKHbGLTe-4-nPwMZl5iNa34wbfDdHkJcgScQ2e_wM_uqFfjNtMoXMJUv-24QayfRdj7xuz7MOc-m-DYNbOzca5GZ2btXOTjZmzbfFQz737S2wlqx90BH4g</recordid><startdate>200505</startdate><enddate>200505</enddate><creator>Arora, Rajesh</creator><creator>Chawla, Raman</creator><creator>Sagar, Ravinder</creator><creator>Prasad, Jagdish</creator><creator>Singh, Surendar</creator><creator>Kumar, Raj</creator><creator>Sharma, Ashok</creator><creator>Singh, Shikha</creator><creator>Sharma, Rakesh Kumar</creator><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200505</creationdate><title>Evaluation of radioprotective activities Rhodiola imbricata Edgew--a high altitude plant</title><author>Arora, Rajesh ; 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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 &lt; 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 &lt; 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 &lt; 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.</abstract><cop>Netherlands</cop><pub>Springer Nature B.V</pub><pmid>16013456</pmid><doi>10.1007/s11010-005-0822-4</doi><tpages>15</tpages></addata></record>
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subjects Absorption
Adult
Altitude
Animals
Anions
Antioxidants
Antioxidants - pharmacology
Aquatic plants
Cell Proliferation - drug effects
Cell Proliferation - radiation effects
Chelation
Chemical analysis
Cobalt Radioisotopes
Erythrocytes - drug effects
Erythrocytes - radiation effects
Free Radical Scavengers - pharmacology
Gamma Rays
Glioma - metabolism
Glioma - pathology
Hemolysis - drug effects
Hemolysis - radiation effects
Humans
Iron
Iron Chelating Agents - pharmacology
Irradiation
Lipid Peroxidation - drug effects
Lipid Peroxidation - radiation effects
Lipids
Liquid chromatography
Male
Mice
Mice, Inbred A
Oxidative Stress
Peroxidation
Plant Extracts - pharmacology
Plants, Medicinal
Radiation-Protective Agents - pharmacology
Rhodiola - chemistry
Rodents
Toluene
Tumor Cells, Cultured
title Evaluation of radioprotective activities Rhodiola imbricata Edgew--a high altitude plant
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