Ontology type: schema:ScholarlyArticle Open Access: True
2018-12
AUTHORSRao Mukkavilli, Chunhua Yang, Reenu Singh Tanwar, Roopali Saxena, Sushma R. Gundala, Yingyi Zhang, Ahmed Ghareeb, Stephan D. Floyd, Subrahmanyam Vangala, Wei-Wen Kuo, Padmashree C. G. Rida, Ritu Aneja
ABSTRACTAnticancer efficacy of ginger phenolics (GPs) has been demonstrated in various in vitro assays and xenograft mouse models. However, only sub-therapeutic plasma concentrations of GPs were detected in human and mouse pharmacokinetic (PK) studies. Intriguingly, a significant portion of GPs occurred as phase II metabolites (mainly glucuronide conjugates) in plasma. To evaluate the disposition of GPs and understand the real players responsible for efficacy, we performed a PK and tissue distribution study in mice. Plasma exposure of GPs was similar on day 1 and 7, suggesting no induction or inhibition of clearance pathways. Both free and conjugated GPs accumulated in all tissues including tumors. While non-cytotoxicity of 6-ginerol glucuronide precluded the role of conjugated GPs in cell death, the free forms were cytotoxic against prostate cancer cells. The efficacy of ginger was best explained by the reconversion of conjugated GPs to free forms by β-glucuronidase, which is over-expressed in the tumor tissue. This previously unrecognized two-step process suggests an instantaneous conversion of ingested free GPs into conjugated forms, followed by their subsequent absorption into systemic circulation and reconversion into free forms. This proposed model uncovers the mechanistic underpinnings of ginger's anticancer activity despite sub-therapeutic levels of free GPs in the plasma. More... »
PAGES3056
http://scigraph.springernature.com/pub.10.1038/s41598-018-21125-2
DOIhttp://dx.doi.org/10.1038/s41598-018-21125-2
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1100925220
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/29445099
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Oncology and Carcinogenesis",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Mukkavilli",
"givenName": "Rao",
"id": "sg:person.01130511606.53",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01130511606.53"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Yang",
"givenName": "Chunhua",
"id": "sg:person.01070356170.49",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01070356170.49"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Tanwar",
"givenName": "Reenu Singh",
"id": "sg:person.0620556217.68",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0620556217.68"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Saxena",
"givenName": "Roopali",
"id": "sg:person.01352635023.04",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01352635023.04"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Gundala",
"givenName": "Sushma R.",
"id": "sg:person.01176446366.91",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01176446366.91"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Zhang",
"givenName": "Yingyi",
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Ghareeb",
"givenName": "Ahmed",
"id": "sg:person.015045073157.45",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.015045073157.45"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Floyd",
"givenName": "Stephan D.",
"type": "Person"
},
{
"affiliation": {
"name": [
"ReaGene Biosciences Private Limited, Bengaluru, India"
],
"type": "Organization"
},
"familyName": "Vangala",
"givenName": "Subrahmanyam",
"id": "sg:person.01361166606.20",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01361166606.20"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "China Medical University",
"id": "https://www.grid.ac/institutes/grid.254145.3",
"name": [
"Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan, ROC"
],
"type": "Organization"
},
"familyName": "Kuo",
"givenName": "Wei-Wen",
"id": "sg:person.01302747166.28",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01302747166.28"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Rida",
"givenName": "Padmashree C. G.",
"id": "sg:person.01133534625.87",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01133534625.87"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Georgia State University",
"id": "https://www.grid.ac/institutes/grid.256304.6",
"name": [
"Department of Biology, Georgia State University, GA-30303, Atlanta, USA"
],
"type": "Organization"
},
"familyName": "Aneja",
"givenName": "Ritu",
"id": "sg:person.01365356361.20",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01365356361.20"
],
"type": "Person"
}
],
"citation": [
{
"id": "https://doi.org/10.1002/jps.1116",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1000852247"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3349/ymj.2006.47.5.688",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001343515"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3349/ymj.2006.47.5.688",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1001343515"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0304-3835(98)00081-0",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1002668039"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1124/pr.111.005439",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1003735630"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1083/jcb.140.5.1255",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1004383944"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.colsurfb.2013.12.056",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1006400751"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1080/10408398209527343",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1008199030"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1093/carcin/bgu011",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1008440098"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1080/10408398209527348",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1009167929"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3390/toxins2040517",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1009377660"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4172/2155-9899.1000238",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1009831301"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.bbrc.2005.07.076",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1012951579"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/0306-9877(80)90035-3",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1015581280"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1097/01.aog.0000217697.33787.8c",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016485305"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1097/01.aog.0000217697.33787.8c",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016485305"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0009-2797(00)00198-8",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016508402"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf00689638",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1018049627",
"https://doi.org/10.1007/bf00689638"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.cccn.2005.02.018",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1021267075"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1201/b10787-8",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1022071571"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3390/molecules14030959",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1027591825"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3109/10409239209082566",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1028450274"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/mnfr.200900409",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1029073198"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3791/960",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032290842"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.cgt.7700999",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032799510",
"https://doi.org/10.1038/sj.cgt.7700999"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.cgt.7700999",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032799510",
"https://doi.org/10.1038/sj.cgt.7700999"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1097/00008469-200610000-00001",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032849506"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1097/00008469-200610000-00001",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032849506"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/1078-0432.ccr-09-0090",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1035685528"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.foodchem.2011.06.026",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1036424852"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.tips.2014.02.001",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1036611717"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.fct.2006.11.002",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037963699"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s002100000260",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1040001588",
"https://doi.org/10.1007/s002100000260"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/1097-0142(19890815)64:4<911::aid-cncr2820640425>3.0.co;2-b",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041164847"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf02975166",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041341388",
"https://doi.org/10.1007/bf02975166"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/bf02975166",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041341388",
"https://doi.org/10.1007/bf02975166"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1080/01635581.2013.749925",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1044284293"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s10495-011-0611-3",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1044341583",
"https://doi.org/10.1007/s10495-011-0611-3"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1590/s1807-59322008000600017",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1046756181"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.4143/crt.2014.46.1.2",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048408184"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1080/10408391003624848",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1048564729"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.12980/apjtb.4.2014c980",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1049228158"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1158/1055-9965.epi-07-2934",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1050119679"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1017/s0007114511003308",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1050150744"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.fct.2010.07.020",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052058111"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1021/np100213a",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1056231205"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1021/np100213a",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1056231205"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.2174/138955710791384081",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1069183165"
],
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1074511955",
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1093/jn/130.5.1124",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1074636579"
],
"type": "CreativeWork"
},
{
"id": "https://app.dimensions.ai/details/publication/pub.1081683091",
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3390/molecules22040553",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1084436681"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.3390/molecules22040553",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1084436681"
],
"type": "CreativeWork"
}
],
"datePublished": "2018-12",
"datePublishedReg": "2018-12-01",
"description": "Anticancer efficacy of ginger phenolics (GPs) has been demonstrated in various in vitro assays and xenograft mouse models. However, only sub-therapeutic plasma concentrations of GPs were detected in human and mouse pharmacokinetic (PK) studies. Intriguingly, a significant portion of GPs occurred as phase II metabolites (mainly glucuronide conjugates) in plasma. To evaluate the disposition of GPs and understand the real players responsible for efficacy, we performed a PK and tissue distribution study in mice. Plasma exposure of GPs was similar on day 1 and 7, suggesting no induction or inhibition of clearance pathways. Both free and conjugated GPs accumulated in all tissues including tumors. While non-cytotoxicity of 6-ginerol glucuronide precluded the role of conjugated GPs in cell death, the free forms were cytotoxic against prostate cancer cells. The efficacy of ginger was best explained by the reconversion of conjugated GPs to free forms by \u03b2-glucuronidase, which is over-expressed in the tumor tissue. This previously unrecognized two-step process suggests an instantaneous conversion of ingested free GPs into conjugated forms, followed by their subsequent absorption into systemic circulation and reconversion into free forms. This proposed model uncovers the mechanistic underpinnings of ginger's anticancer activity despite sub-therapeutic levels of free GPs in the plasma.",
"genre": "research_article",
"id": "sg:pub.10.1038/s41598-018-21125-2",
"inLanguage": [
"en"
],
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.2482030",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1045337",
"issn": [
"2045-2322"
],
"name": "Scientific Reports",
"type": "Periodical"
},
{
"issueNumber": "1",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "8"
}
],
"name": "Pharmacokinetic-pharmacodynamic correlations in the development of ginger extract as an anticancer agent",
"pagination": "3056",
"productId": [
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"8e7f68a955b702cf3f4ca810f50a5938778d072867d1fa5ebd8700892e89e637"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"29445099"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"101563288"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1038/s41598-018-21125-2"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1100925220"
]
}
],
"sameAs": [
"https://doi.org/10.1038/s41598-018-21125-2",
"https://app.dimensions.ai/details/publication/pub.1100925220"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-10T21:00",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8684_00000603.jsonl",
"type": "ScholarlyArticle",
"url": "https://www.nature.com/articles/s41598-018-21125-2"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21125-2'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21125-2'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21125-2'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21125-2'
This table displays all metadata directly associated to this object as RDF triples.
291 TRIPLES
21 PREDICATES
75 URIs
21 LITERALS
9 BLANK NODES