;PMID: 8561796 ;source_file_1790.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..53] = [t:0..53] ;1)sentence:[e:59..230] = [t:59..230] ;2)section:[e:234..283] = [t:234..283] ;3)section:[e:287..364] = [t:287..364] ;4)sentence:[e:368..502] = [t:368..502] ;5)sentence:[e:503..625] = [t:503..625] ;6)sentence:[e:626..752] = [t:626..752] ;7)sentence:[e:753..851] = [t:753..851] ;8)sentence:[e:853..1069] = [t:853..1069] ;9)sentence:[e:1070..1164] = [t:1070..1164] ;10)sentence:[e:1165..1240] = [t:1165..1240] ;11)sentence:[e:1242..1334] = [t:1242..1334] ;12)sentence:[e:1335..1480] = [t:1335..1480] ;13)sentence:[e:1481..1558] = [t:1481..1558] ;14)sentence:[e:1559..1829] = [t:1559..1829] ;15)section:[e:1833..1877] = [t:1833..1877] ;section 0 Span:0..53 ;Biochem Biophys Res Commun. 1996 Jan 17;218(2):562-9. (SEC (FRAG (NNP:[0..7] Biochem) (NNP:[8..15] Biophys) (NNP:[16..19] Res) (NNP:[20..26] Commun) (.:[26..27] .) (CD:[28..32] 1996) (CC:[33..36] Jan) (CD:[37..43] 17;218) (-LRB-:[43..44] -LRB-) (CD:[44..45] 2) (-RRB-:[45..46] -RRB-) (::[46..47] :) (CD:[47..50] 562) (::[50..51] -) (CD:[51..53] 9.))) ;sentence 1 Span:59..230 ;Piperine impairs cytochrome P4501A1 activity by direct interaction with the ;enzyme and not by down regulation of CYP1A1 gene expression in the rat ;hepatoma 5L cell line. ;[59..67]:substance:"Piperine" ;[76..94]:cyp450:"cytochrome P4501A1" ;[136..142]:cyp450:"enzyme" ;[173..179]:cyp450:"CYP1A1" (SENT (S-HLN (NP-SBJ (NN:[59..67] Piperine)) (VP (VBZ:[68..75] impairs) (NP (NML (NN:[76..86] cytochrome) (NN:[87..94] P4501A1)) (NN:[95..103] activity)) (PP-MNR (PP (IN:[104..106] by) (NP (NP (JJ:[107..113] direct) (NN:[114..125] interaction)) (PP (IN:[126..130] with) (NP (DT:[131..134] the) (NN:[136..142] enzyme))))) (CONJP (CC:[143..146] and) (RB:[147..150] not)) (PP (IN:[151..153] by) (NP (NP (RB:[154..158] down) (NN:[159..169] regulation)) (PP (IN:[170..172] of) (NP (NN:[173..179] CYP1A1) (NN:[180..184] gene) (NN:[185..195] expression))) (PP-LOC (IN:[196..198] in) (NP (DT:[199..202] the) (NN:[203..206] rat) (NN:[207..215] hepatoma) (NN:[217..219] 5L) (NN:[220..224] cell) (NN:[225..229] line))))))) (.:[229..230] .))) ;section 2 Span:234..283 ;Reen RK, Roesch SF, Kiefer F, Wiebel FJ, Singh J. (SEC (FRAG (NNP:[234..238] Reen) (NNP:[239..241] RK) (,:[241..242] ,) (NNP:[243..249] Roesch) (NNP:[250..252] SF) (,:[252..253] ,) (NNP:[254..260] Kiefer) (NNP:[261..262] F) (,:[262..263] ,) (NNP:[264..270] Wiebel) (NNP:[271..273] FJ) (,:[273..274] ,) (NNP:[275..280] Singh) (NNP:[281..283] J.))) ;section 3 Span:287..364 ;Biochemistry Section, Regional Research Laboratory (CSIR), Jammu Tawi, ;India. (SEC (FRAG (NNP:[287..299] Biochemistry) (NNP:[300..307] Section) (,:[307..308] ,) (NNP:[309..317] Regional) (NNP:[318..326] Research) (NNP:[327..337] Laboratory) (-LRB-:[338..339] -LRB-) (NNP:[339..343] CSIR) (-RRB-:[343..344] -RRB-) (,:[344..345] ,) (NNP:[346..351] Jammu) (NNP:[352..356] Tawi) (,:[356..357] ,) (NNP:[358..363] India) (.:[363..364] .))) ;sentence 4 Span:368..502 ;Modulation of benzo(a)pyrene (BP) metabolism and regulation of CYP1A1 gene ;expression by piperine in 5L cells in culture was studied. ;[382..396]:substance:"benzo(a)pyrene" ;[398..400]:substance:"BP" ;[431..437]:cyp450:"CYP1A1" ;[458..466]:substance:"piperine" (SENT (S (NP-SBJ-1 (NP (NP (NP (NN:[368..378] Modulation)) (PP (IN:[379..381] of) (NP (NML (NML (NN:[382..396] benzo-LRB-a-RRB-pyrene)) (NML (-LRB-:[397..398] -LRB-) (NN:[398..400] BP) (-RRB-:[400..401] -RRB-))) (NN:[402..412] metabolism)))) (CC:[413..416] and) (NP (NP (NN:[417..427] regulation)) (PP (IN:[428..430] of) (NP (NN:[431..437] CYP1A1) (NN:[438..442] gene) (NN:[444..454] expression))))) (PP (IN:[455..457] by) (NP (NN:[458..466] piperine))) (PP-LOC (IN:[467..469] in) (NP (NP (NN:[470..472] 5L) (NNS:[473..478] cells)) (PP-LOC (IN:[479..481] in) (NP (NN:[482..489] culture)))))) (VP (VBD:[490..493] was) (VP (VBN:[494..501] studied) (NP-1 (-NONE-:[501..501] *)))) (.:[501..502] .))) ;sentence 5 Span:503..625 ;Treatment of cultures with 60 microM piperine for different time periods ;inhibited metabolism of BP by 50% within 4-8 h. ;[531..533]:quantitative-value:"60" ;[534..540]:quantitative-units:"microM" ;[541..549]:substance:"piperine" ;[601..603]:substance:"BP" ;[608..611]:quantitative-value:"50%" ;[619..622]:quantitative-value:"4-8" ;[623..624]:quantitative-units:"h" (SENT (S (NP-SBJ (NP (NN:[503..512] Treatment)) (PP (IN:[513..515] of) (NP (NNS:[516..524] cultures))) (PP (IN:[526..530] with) (NP (NML (CD:[531..533] 60) (NN:[534..540] microM)) (NN:[541..549] piperine))) (PP (IN:[550..553] for) (NP (JJ:[554..563] different) (NN:[564..568] time) (NNS:[569..576] periods)))) (VP (VBD:[577..586] inhibited) (NP (NP (NN:[587..597] metabolism)) (PP (IN:[598..600] of) (NP (NN:[601..603] BP)))) (PP-EXT (IN:[604..606] by) (NP (CD:[608..610] 50) (NN:[610..611] %))) (PP-TMP (IN:[612..618] within) (NP (QP (CD:[619..620] 4) (HYPH:[620..621] -) (CD:[621..622] 8)) (NN:[623..624] h)))) (.:[624..625] .))) ;sentence 6 Span:626..752 ;Piperine uptake in 5L cells attained saturation plateau at 8 h and this ;related with the maximal impairment of BP metabolism. ;[626..634]:substance:"Piperine" ;[685..686]:quantitative-value:"8" ;[687..688]:quantitative-units:"h" ;[738..740]:substance:"BP" (SENT (S (S (NP-SBJ (NP (NN:[626..634] Piperine) (NN:[635..641] uptake)) (PP-LOC (IN:[642..644] in) (NP (NN:[645..647] 5L) (NNS:[648..653] cells)))) (VP (VBD:[654..662] attained) (NP (NN:[663..673] saturation) (NN:[674..681] plateau)) (PP-TMP (IN:[682..684] at) (NP (CD:[685..686] 8) (NN:[687..688] h))))) (CC:[690..693] and) (S (NP-SBJ (DT:[694..698] this)) (VP (VBD:[699..706] related) (PP-CLR (IN:[707..711] with) (NP (NP (DT:[712..715] the) (JJ:[716..723] maximal) (NN:[724..734] impairment)) (PP (IN:[735..737] of) (NP (NN:[738..740] BP) (NN:[741..751] metabolism))))))) (.:[751..752] .))) ;sentence 7 Span:753..851 ;Exposure of cell cultures to piperine for 24 h indicated activation of ;CYP1A1 gene transcription. ;[783..791]:substance:"piperine" ;[796..798]:quantitative-value:"24" ;[799..800]:quantitative-units:"h" ;[825..831]:cyp450:"CYP1A1" (SENT (S (NP-SBJ (NP (NN:[753..761] Exposure)) (PP (IN:[762..764] of) (NP (NN:[765..769] cell) (NNS:[771..779] cultures))) (PP (TO:[780..782] to) (NP (NN:[783..791] piperine))) (PP-TMP (IN:[792..795] for) (NP (CD:[796..798] 24) (NN:[799..800] h)))) (VP (VBD:[801..810] indicated) (NP (NP (NN:[811..821] activation)) (PP (IN:[822..824] of) (NP (NN:[825..831] CYP1A1) (NN:[832..836] gene) (NN:[837..850] transcription))))) (.:[850..851] .))) ;sentence 8 Span:853..1069 ;There was a 10-fold increase in CYP1A1mRNA and an approximately 7-fold ;increase in arylhydrocarbon hydroxylase (AHH) activity, while treatment with ; benzanthacene (BA) increased CYP1A1mRNA by 86- and AHH by 56-fold. ;[865..872]:quantitative-value:"10-fold" ;[885..895]:substance:"CYP1A1mRNA" ;[903..923]:quantitative-value:"approximately 7-fold" ;[937..964]:substance:"arylhydrocarbon hydroxylase" ;[966..969]:substance:"AHH" ;[1003..1016]:substance:"benzanthacene" ;[1018..1020]:substance:"BA" ;[1032..1042]:substance:"CYP1A1mRNA" ;[1046..1049]...[1064..1068]:quantitative-value:"86-"..."fold" ;[1054..1057]:substance:"AHH" ;[1061..1068]:quantitative-value:"56-fold" (SENT (S (NP-SBJ (EX:[853..858] There)) (VP (VBD:[859..862] was) (NP-PRD (NP (NP (DT:[863..864] a) (QP (CD:[865..867] 10) (HYPH:[867..868] -) (JJ:[868..872] fold)) (NN:[873..881] increase)) (PP (IN:[882..884] in) (NP (NN:[885..895] CYP1A1mRNA)))) (CC:[896..899] and) (NP (NP (DT:[900..902] an) (QP (RB:[903..916] approximately) (CD:[917..918] 7) (HYPH:[918..919] -) (JJ:[919..923] fold)) (NN:[924..932] increase)) (PP (IN:[934..936] in) (NP (NML (NML (NN:[937..952] arylhydrocarbon) (NN:[953..964] hydroxylase)) (NP (-LRB-:[965..966] -LRB-) (NN:[966..969] AHH) (-RRB-:[969..970] -RRB-))) (NN:[971..979] activity))))) (,:[979..980] ,) (SBAR-ADV (IN:[981..986] while) (S (NP-SBJ (NP (NN:[987..996] treatment)) (PP (IN:[997..1001] with) (NP (NP (NN:[1003..1016] benzanthacene)) (NP (-LRB-:[1017..1018] -LRB-) (NN:[1018..1020] BA) (-RRB-:[1020..1021] -RRB-))))) (VP (VP (VBD:[1022..1031] increased) (NP=3 (NN:[1032..1042] CYP1A1mRNA)) (PP=4 (IN:[1043..1045] by) (ADVP-EXT (CD:[1046..1048] 86) (HYPH:[1048..1049] -) (ADVP-1 (-NONE-:[1049..1049] *RNR*))))) (CC:[1050..1053] and) (VP (NP=3 (NN:[1054..1057] AHH)) (PP=4 (IN:[1058..1060] by) (ADVP-EXT (CD:[1061..1063] 56) (HYPH:[1063..1064] -) (ADVP-1 (-NONE-:[1064..1064] *RNR*))))) (ADVP-1 (RB:[1064..1068] fold)))))) (.:[1068..1069] .))) ;sentence 9 Span:1070..1164 ;Combined treatment with BA plus piperine further increased CYP1A1mRNA ;contents by about 25%. ;[1095..1097]:substance:"BA" ;[1103..1111]:substance:"piperine" ;[1130..1140]:substance:"CYP1A1mRNA" ;[1153..1163]:quantitative-value:"about 25%" (SENT (S (NP-SBJ (NP (VBN:[1070..1078] Combined) (NN:[1080..1089] treatment)) (PP (IN:[1090..1094] with) (NP (NN:[1095..1097] BA) (CC:[1098..1102] plus) (NN:[1103..1111] piperine)))) (ADVP (RBR:[1112..1119] further)) (VP (VBD:[1120..1129] increased) (NP (NN:[1130..1140] CYP1A1mRNA) (NNS:[1141..1149] contents)) (PP-EXT (IN:[1150..1152] by) (NP (QP (RB:[1153..1158] about) (CD:[1160..1162] 25)) (NN:[1162..1163] %)))) (.:[1163..1164] .))) ;sentence 10 Span:1165..1240 ;The BA-inducible AHH activity, however, registered a decrease of about 45%. ;[1169..1171]:substance:"BA" ;[1182..1185]:substance:"AHH" ;[1230..1239]:quantitative-value:"about 45%" (SENT (S (NP-SBJ (DT:[1165..1168] The) (ADJP (NN:[1169..1171] BA) (HYPH:[1171..1172] -) (JJ:[1172..1181] inducible)) (NN:[1182..1185] AHH) (NN:[1186..1194] activity)) (,:[1194..1195] ,) (ADVP (RB:[1196..1203] however)) (,:[1203..1204] ,) (VP (VBD:[1205..1215] registered) (NP (NP (DT:[1216..1217] a) (NN:[1218..1226] decrease)) (PP (IN:[1227..1229] of) (NP (QP (RB:[1230..1235] about) (CD:[1236..1238] 45)) (NN:[1238..1239] %))))) (.:[1239..1240] .))) ;sentence 11 Span:1242..1334 ;Piperine neither destroyed CYP1A1-protein nor affected the total cellular ;protein contents. ;[1242..1250]:substance:"Piperine" ;[1269..1283]:cyp450:"CYP1A1-protein" ;[1317..1324]:substance:"protein" (SENT (S (NP-SBJ (NN:[1242..1250] Piperine)) (VP (CC:[1251..1258] neither) (VP (VBD:[1259..1268] destroyed) (NP (NN:[1269..1275] CYP1A1) (HYPH:[1275..1276] -) (NN:[1276..1283] protein))) (CC:[1284..1287] nor) (VP (VBD:[1288..1296] affected) (NP (DT:[1297..1300] the) (JJ:[1301..1306] total) (JJ:[1307..1315] cellular) (NN:[1317..1324] protein) (NNS:[1325..1333] contents)))) (.:[1333..1334] .))) ;sentence 12 Span:1335..1480 ;Exposure of cultures to 0.01 to 3.0 microM ;trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene for 24 h reduced maximum ;cellular growth by about 50%. ;[1359..1370]:quantitative-value:"0.01 to 3.0" ;[1371..1377]:quantitative-units:"microM" ;[1379..1424]:substance:"trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene" ;[1429..1431]:quantitative-value:"24" ;[1432..1433]:quantitative-units:"h" ;[1470..1479]:quantitative-value:"about 50%" (SENT (S (NP-SBJ (NP (NN:[1335..1343] Exposure)) (PP (IN:[1344..1346] of) (NP (NNS:[1347..1355] cultures))) (PP (TO:[1356..1358] to) (NP (NML (QP (CD:[1359..1363] 0.01) (TO:[1364..1366] to) (CD:[1367..1370] 3.0)) (NN:[1371..1377] microM)) (NN:[1379..1424] trans-7,8-dihydroxy-7,8-dihydrobenzo-LRB-a-RRB-pyrene))) (PP-TMP (IN:[1425..1428] for) (NP (CD:[1429..1431] 24) (NN:[1432..1433] h)))) (VP (VBD:[1434..1441] reduced) (NP (JJ:[1442..1449] maximum) (JJ:[1450..1458] cellular) (NN:[1460..1466] growth)) (PP-EXT (IN:[1467..1469] by) (NP (QP (RB:[1470..1475] about) (CD:[1476..1478] 50)) (NN:[1478..1479] %)))) (.:[1479..1480] .))) ;sentence 13 Span:1481..1558 ;Piperine at 60 microM offered full protection against the diol ;cytotoxicity. ;[1481..1489]:substance:"Piperine" ;[1493..1495]:quantitative-value:"60" ;[1496..1502]:quantitative-units:"microM" ;[1540..1544]:substance:"diol" (SENT (S (NP-SBJ (NP (NN:[1481..1489] Piperine)) (PP (IN:[1490..1492] at) (NP (CD:[1493..1495] 60) (NN:[1496..1502] microM)))) (VP (VBD:[1503..1510] offered) (NP (NP (JJ:[1511..1515] full) (NN:[1516..1526] protection)) (PP (IN:[1527..1534] against) (NP (DT:[1535..1538] the) (NN:[1540..1544] diol) (NN:[1545..1557] cytotoxicity))))) (.:[1557..1558] .))) ;sentence 14 Span:1559..1829 ;The results, suggest that piperine mediated inhibition of the AHH activity ;and consequent suppression of the procarcinogen activation is the result of ;direct interaction of piperine with CYP1A1-protein and not because of down ;regulation of the CYP1A1 gene expression. ;[1585..1593]:substance:"piperine" ;[1622..1625]:substance:"AHH" ;[1669..1682]:substance:"procarcinogen" ;[1734..1742]:substance:"piperine" ;[1748..1762]:cyp450:"CYP1A1-protein" ;[1806..1812]:cyp450:"CYP1A1" (SENT (S (NP-SBJ (DT:[1559..1562] The) (NNS:[1563..1570] results)) (,:[1570..1571] ,) (VP (VBP:[1572..1579] suggest) (SBAR (IN:[1580..1584] that) (S (NP-SBJ (NP (NP (ADJP (NN:[1585..1593] piperine) (VBN:[1594..1602] mediated)) (NN:[1603..1613] inhibition)) (PP (IN:[1614..1616] of) (NP (DT:[1617..1620] the) (NN:[1622..1625] AHH) (NN:[1626..1634] activity)))) (CC:[1635..1638] and) (NP (NP (JJ:[1639..1649] consequent) (NN:[1650..1661] suppression)) (PP (IN:[1662..1664] of) (NP (DT:[1665..1668] the) (NN:[1669..1682] procarcinogen) (NN:[1683..1693] activation))))) (VP (VP (VBZ:[1694..1696] is) (NP-PRD=1 (NP (DT:[1697..1700] the) (NN:[1702..1708] result)) (PP (IN:[1709..1711] of) (NP (NP (JJ:[1712..1718] direct) (NN:[1719..1730] interaction)) (PP (IN:[1731..1733] of) (NP (NN:[1734..1742] piperine))) (PP (IN:[1743..1747] with) (NP (NN:[1748..1754] CYP1A1) (HYPH:[1754..1755] -) (NN:[1755..1762] protein))))))) (CC:[1763..1766] and) (VP (RB:[1767..1770] not) (PP-PRD=1 (IN:[1771..1778] because) (IN:[1779..1781] of) (NP (NP (RB:[1783..1787] down) (NN:[1788..1798] regulation)) (PP (IN:[1799..1801] of) (NP (DT:[1802..1805] the) (NN:[1806..1812] CYP1A1) (NN:[1813..1817] gene) (NN:[1818..1828] expression)))))))))) (.:[1828..1829] .))) ;section 15 Span:1833..1877 ;PMID: 8561796 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1833..1837] PMID) (::[1837..1838] :) (CD:[1839..1846] 8561796) (NN:[1847..1848] -LSB-) (NNP:[1848..1854] PubMed) (::[1855..1856] -) (NN:[1857..1864] indexed) (IN:[1865..1868] for) (NNP:[1869..1877] MEDLINE-RSB-)))