0 9 Helenalin Helenalin NNP 9 10 , , , 11 13 an an DT 14 31 anti-inflammatory anti-inflammatory JJ 32 45 sesquiterpene sesquiterpene NN 46 53 lactone lactone NN 54 58 from from IN 59 65 Arnica Arnica NNP 65 66 , , , 67 78 selectively selectively RB 79 87 inhibits inhibit VBZ 88 101 transcription transcription NN 102 108 factor factor NN 109 118 NF-kappaB NF-kappaB NNP 119 120 [ [ ( 120 123 see see VB 124 132 comments comment NNS 132 133 ] ] ) 135 144 Alcoholic alcoholic JJ 145 153 extracts extract NNS 154 162 prepared prepare VBN 163 167 form form NN 168 175 Arnicae arnicae FW 176 180 flos flos FW 180 181 , , , 182 185 the the DT 186 196 collective collective JJ 197 201 name name NN 202 205 for for IN 206 217 flowerheads flowerhead NNS 218 222 from from IN 223 229 Arnica Arnica NNP 230 237 montana montana NN 238 241 and and CC 242 244 A. a. NN 245 256 chamissonis chamissonis NN 257 261 ssp. ssp. NN 262 269 foliosa foliosa NN 269 270 , , , 271 274 are be VBP 275 279 used use VBN 280 295 therapeutically therapeutically RB 296 298 as as IN 299 316 anti-inflammatory anti-inflammatory JJ 317 325 remedies remedy NNS 325 326 . . . 327 330 The the DT 331 337 active active JJ 338 349 ingredients ingredient NNS 350 359 mediating mediate VBG 360 363 the the DT 364 379 pharmacological pharmacological JJ 380 386 effect effect NN 387 390 are be VBP 391 397 mainly mainly RB 398 411 sesquiterpene sesquiterpene NN 412 420 lactones lactone NNS 420 421 , , , 422 426 such such JJ 427 429 as as IN 430 439 helenalin helenalin NN 439 440 , , , 441 468 11alpha,13-dihydrohelenalin 11alpha,13-dihydrohelenalin NN 468 469 , , , 470 483 chamissonolid chamissonolid NN 484 487 and and CC 488 493 their their PRP$ 494 499 ester ester NN 500 511 derivatives derivative NNS 511 512 . . . 513 518 While while IN 519 524 these these DT 525 534 compounds compound NNS 535 541 affect affect VBP 542 549 various various JJ 550 558 cellular cellular JJ 559 568 processes process NNS 568 569 , , , 570 577 current current JJ 578 582 data datum NNS 583 585 do do VBP 586 589 not not RB 590 595 fully fully RB 596 603 explain explain VB 604 607 how how WRB 608 621 sesquiterpene sesquiterpene NN 622 630 lactones lactone NNS 631 636 exert exert VBP 637 642 their their PRP$ 643 660 anti-inflammatory anti-inflammatory JJ 661 667 effect effect NN 667 668 . . . 669 671 We we PRP 672 676 show show VBP 677 681 here here RB 682 686 that that IN 687 696 helenalin helenalin NN 696 697 , , , 698 701 and and CC 701 702 , , , 703 705 to to TO 706 707 a a DT 708 712 much much RB 713 719 lesser less JJR 720 726 degree degree NN 726 727 , , , 728 755 11alpha,13-dihydrohelenalin 11alpha,13-dihydrohelenalin NN 756 759 and and CC 760 773 chamissonolid chamissonolid NN 773 774 , , , 775 782 inhibit inhibit VBP 783 793 activation activation NN 794 796 of of IN 797 810 transcription transcription NN 811 817 factor factor NN 818 827 NF-kappaB nf-kappab NN 827 828 . . . 829 833 This this DT 834 844 difference difference NN 845 847 in in IN 848 856 efficacy efficacy NN 856 857 , , , 858 863 which which WDT 864 874 correlates correlate VBZ 875 879 with with IN 880 883 the the DT 884 893 compounds compound NNS 893 894 ’ ' POS 895 912 anti-inflammatory anti-inflammatory JJ 913 920 potency potency NN 921 923 in in FW 924 928 vivo vivo FW 928 929 , , , 930 933 may may MD 934 936 be be VB 937 946 explained explain VBN 947 949 by by IN 950 961 differences difference NNS 962 964 in in IN 965 974 structure structure NN 975 978 and and CC 979 991 conformation conformation NN 991 992 . . . 993 1002 NF-kappaB NF-kappaB NNP 1002 1003 , , , 1004 1009 which which WDT 1010 1017 resides reside VBZ 1018 1020 in in IN 1021 1023 an an DT 1024 1032 inactive inactive JJ 1032 1033 , , , 1034 1045 cytoplasmic cytoplasmic JJ 1046 1053 complex complex NN 1054 1056 in in IN 1057 1069 unstimulated unstimulated JJ 1070 1075 cells cell NNS 1075 1076 , , , 1077 1079 is be VBZ 1080 1089 activated activate VBN 1090 1092 by by IN 1093 1108 phosphorylation phosphorylation NN 1109 1112 and and CC 1113 1124 degradation degradation NN 1125 1127 of of IN 1128 1131 its its PRP$ 1132 1142 inhibitory inhibitory JJ 1143 1150 subunit subunit NN 1150 1151 , , , 1152 1159 IkappaB IkappaB NNP 1159 1160 . . . 1161 1170 Helenalin Helenalin NNP 1171 1179 inhibits inhibit VBZ 1180 1189 NF-kappaB NF-kappaB NNP 1190 1200 activation activation NN 1201 1203 in in IN 1204 1212 response response NN 1213 1215 to to TO 1216 1220 four four CD 1221 1230 different different JJ 1231 1238 stimuli stimulus NNS 1239 1241 in in IN 1242 1249 T-cells T-cell NNP 1249 1250 , , , 1251 1258 B-cells B-cell NNP 1259 1262 and and CC 1263 1273 epithelial epithelial JJ 1274 1279 cells cell NNS 1280 1283 and and CC 1284 1293 abrogates abrogate VBZ 1294 1307 kappaB-driven kappab-driven JJ 1308 1312 gene gene NN 1313 1323 expression expression NN 1323 1324 . . . 1325 1329 This this DT 1330 1340 inhibition inhibition NN 1341 1343 is be VBZ 1344 1353 selective selective JJ 1353 1354 , , , 1355 1357 as as IN 1358 1361 the the DT 1362 1370 activity activity NN 1371 1373 of of IN 1374 1378 four four CD 1379 1384 other other JJ 1385 1398 transcription transcription NN 1399 1406 factors factor NNS 1406 1407 , , , 1408 1413 Oct-1 Oct-1 NNP 1413 1414 , , , 1415 1418 TBP TBP NNP 1418 1419 , , , 1420 1423 Sp1 Sp1 NNP 1424 1427 and and CC 1428 1432 STAT STAT NNP 1433 1434 5 5 CD 1435 1438 was be VBD 1439 1442 not not RB 1443 1451 affected affect VBN 1451 1452 . . . 1453 1455 We we PRP 1456 1460 show show VBP 1461 1465 that that IN 1466 1476 inhibition inhibition NN 1477 1479 is be VBZ 1480 1483 not not RB 1484 1487 due due JJ 1488 1490 to to TO 1491 1492 a a DT 1493 1499 direct direct JJ 1500 1512 modification modification NN 1513 1515 of of IN 1516 1519 the the DT 1520 1526 active active JJ 1527 1536 NF-kappaB nf-kappab NN 1537 1548 heterodimer heterodimer NN 1548 1549 . . . 1550 1556 Rather rather RB 1556 1557 , , , 1558 1567 helenalin helenalin NN 1568 1576 modifies modify VBZ 1577 1580 the the DT 1581 1598 NF-kappaB/IkappaB NF-kappaB/IkappaB NNP 1599 1606 complex complex NN 1606 1607 , , , 1608 1618 preventing prevent VBG 1619 1622 the the DT 1623 1630 release release NN 1631 1633 of of IN 1634 1641 IkappaB IkappaB NNP 1641 1642 . . . 1643 1648 These these DT 1649 1653 data datum NNS 1654 1661 suggest suggest VBP 1662 1663 a a DT 1664 1673 molecular molecular JJ 1674 1683 mechanism mechanism NN 1684 1687 for for IN 1688 1691 the the DT 1692 1709 anti-inflammatory anti-inflammatory JJ 1710 1716 effect effect NN 1717 1719 of of IN 1720 1733 sesquiterpene sesquiterpene NN 1734 1742 lactones lactone NNS 1742 1743 , , , 1744 1749 which which WDT 1750 1757 differs differ VBZ 1758 1762 from from IN 1763 1767 that that DT 1768 1770 of of IN 1771 1776 other other JJ 1777 1789 nonsteroidal nonsteroidal JJ 1790 1807 anti-inflammatory anti-inflammatory JJ 1808 1813 drugs drug NNS 1814 1815 ( ( ( 1815 1821 NSAIDs NSAID NNP 1821 1822 ) ) ) 1822 1823 , , , 1824 1836 indomethacin indomethacin NN 1837 1840 and and CC 1841 1847 acetyl acetyl NN 1848 1857 salicylic salicylic JJ 1858 1862 acid acid NN 1862 1863 . . .