0 6 Potent potent JJ 7 17 inhibition inhibition NN 18 20 of of IN 21 24 HIV HIV NNP 25 29 type type NN 30 31 1 1 CD 32 43 replication replication NN 44 46 by by IN 47 49 an an DT 50 66 antiinflammatory antiinflammatory JJ 67 75 alkaloid alkaloid NN 75 76 , , , 77 90 cepharanthine cepharanthine NN 90 91 , , , 92 94 in in IN 95 106 chronically chronically RB 107 115 infected infected JJ 116 125 monocytic monocytic JJ 126 131 cells cell NNS 131 132 . . . 134 147 Cepharanthine Cepharanthine NNP 148 150 is be VBZ 151 152 a a DT 153 166 biscoclaurine biscoclaurine NN 167 175 alkaloid alkaloid NN 176 184 isolated isolate VBN 185 189 from from IN 190 199 Stephania Stephania NNP 200 211 cepharantha cepharantha NN 212 218 Hayata Hayata NNP 219 222 and and CC 223 226 has have VBZ 227 231 been be VBN 232 237 shown show VBN 238 240 to to TO 241 245 have have VB 246 262 antiinflammatory antiinflammatory JJ 262 263 , , , 264 276 antiallergic antiallergic JJ 276 277 , , , 278 281 and and CC 282 298 immunomodulatory immunomodulatory JJ 299 309 activities activity NNS 310 312 in in FW 313 317 vivo vivo FW 317 318 . . . 319 321 As as IN 322 329 several several JJ 330 342 inflammatory inflammatory JJ 343 352 cytokines cytokine NNS 353 356 and and CC 357 366 oxidative oxidative JJ 367 375 stresses stress NNS 376 379 are be VBP 380 388 involved involve VBN 389 391 in in IN 392 395 the the DT 396 408 pathogenesis pathogenesis NN 409 411 of of IN 412 417 HIV-1 HIV-1 NNP 418 427 infection infection NN 427 428 , , , 429 431 we we PRP 432 444 investigated investigate VBD 445 448 the the DT 449 459 inhibitory inhibitory JJ 460 467 effects effect NNS 468 470 of of IN 471 484 cepharanthine cepharanthine NN 485 487 on on IN 488 493 tumor tumor NN 494 502 necrosis necrosis NN 503 509 factor factor NN 510 515 alpha alpha NN 516 517 ( ( ( 517 528 TNF-alpha)- tnf-alpha)- NN 529 532 and and CC 533 540 phorbol phorbol NN 541 553 12-myristate 12-myristate NN 554 564 13-acetate 13-acetate NN 565 566 ( ( ( 566 578 PMA)-induced pma)-induced JJ 579 584 HIV-1 HIV-1 NNP 585 596 replication replication NN 597 599 in in IN 600 611 chronically chronically RB 612 620 infected infected JJ 621 625 cell cell NN 626 631 lines line NNS 631 632 . . . 633 636 Two two CD 637 648 chronically chronically RB 649 663 HIV-1-infected hiv-1-infected JJ 664 668 cell cell NN 669 674 lines line NNS 674 675 , , , 676 678 U1 u1 NN 679 680 ( ( ( 680 689 monocytic monocytic JJ 689 690 ) ) ) 691 694 and and CC 695 700 ACH-2 ach-2 NN 701 702 ( ( ( 702 703 T t NN 704 715 lymphocytic lymphocytic JJ 715 716 ) ) ) 716 717 , , , 718 722 were be VBD 723 733 stimulated stimulate VBN 734 738 with with IN 739 748 TNF-alpha TNF-alpha NNP 749 751 or or CC 752 755 PMA PMA NNP 756 759 and and CC 760 768 cultured culture VBN 769 771 in in IN 772 775 the the DT 776 784 presence presence NN 785 787 of of IN 788 795 various various JJ 796 810 concentrations concentration NNS 811 813 of of IN 814 817 the the DT 818 826 compound compound NN 826 827 . . . 828 833 HIV-1 HIV-1 NNP 834 845 replication replication NN 846 849 was be VBD 850 860 determined determine VBN 861 863 by by IN 864 867 p24 p24 NN 868 875 antigen antigen NN 876 881 level level NN 881 882 . . . 883 886 The the DT 887 897 inhibitory inhibitory JJ 898 905 effects effect NNS 906 908 of of IN 909 922 cepharanthine cepharanthine NN 923 925 on on IN 926 931 HIV-1 HIV-1 NNP 932 936 long long JJ 937 945 terminal terminal JJ 946 952 repeat repeat NN 953 954 ( ( ( 954 965 LTR)-driven ltr)-driven JJ 966 970 gene gene NN 971 981 expression expression NN 982 985 and and CC 986 993 nuclear nuclear JJ 994 1000 factor factor NN 1001 1007 kappaB kappaB NNP 1008 1009 ( ( ( 1009 1018 NF-kappaB NF-kappaB NNP 1018 1019 ) ) ) 1020 1030 activation activation NN 1031 1035 were be VBD 1036 1040 also also RB 1041 1049 examined examine VBN 1049 1050 . . . 1051 1064 Cepharanthine Cepharanthine NNP 1065 1069 dose dose NN 1070 1081 dependently dependently RB 1082 1091 inhibited inhibit VBD 1092 1097 HIV-1 HIV-1 NNP 1098 1109 replication replication NN 1110 1112 in in IN 1113 1123 TNF-alpha- tnf-alpha- NN 1124 1127 and and CC 1128 1142 PMA-stimulated pma-stimulated JJ 1143 1145 U1 u1 NN 1146 1151 cells cell NNS 1152 1155 but but CC 1156 1159 not not RB 1160 1162 in in IN 1163 1168 ACH-2 ach-2 NN 1169 1174 cells cell NNS 1174 1175 . . . 1176 1179 Its its PRP$ 1180 1182 50 50 CD 1182 1183 % % NN 1184 1193 effective effective JJ 1194 1197 and and CC 1198 1207 cytotoxic cytotoxic JJ 1208 1222 concentrations concentration NNS 1223 1227 were be VBD 1228 1233 0.016 0.016 CD 1234 1237 and and CC 1238 1241 2.2 2.2 CD 1242 1251 microg/ml microg/ml NN 1252 1254 in in IN 1255 1269 PMA-stimulated pma-stimulated JJ 1270 1272 U1 u1 NN 1273 1278 cells cell NNS 1278 1279 , , , 1280 1292 respectively respectively RB 1292 1293 . . . 1294 1307 Cepharanthine Cepharanthine NNP 1308 1311 was be VBD 1312 1317 found find VBN 1318 1320 to to TO 1321 1329 suppress suppress VB 1330 1335 HIV-1 HIV-1 NNP 1336 1346 LTR-driven ltr-driven JJ 1347 1351 gene gene NN 1352 1362 expression expression NN 1363 1370 through through IN 1371 1374 the the DT 1375 1385 inhibition inhibition NN 1386 1388 of of IN 1389 1398 NF-kappaB NF-kappaB NNP 1399 1409 activation activation NN 1409 1410 . . . 1411 1416 These these DT 1417 1424 results result NNS 1425 1433 indicate indicate VBP 1434 1438 that that IN 1439 1452 cepharanthine cepharanthine NN 1453 1455 is be VBZ 1456 1457 a a DT 1458 1464 highly highly RB 1465 1471 potent potent JJ 1472 1481 inhibitor inhibitor NN 1482 1484 of of IN 1485 1490 HIV-1 HIV-1 NNP 1491 1502 replication replication NN 1503 1505 in in IN 1506 1507 a a DT 1508 1519 chronically chronically RB 1520 1528 infected infected JJ 1529 1538 monocytic monocytic JJ 1539 1543 cell cell NN 1544 1548 line line NN 1548 1549 . . . 1550 1555 Since since IN 1556 1569 biscoclaurine biscoclaurine NN 1570 1579 alkaloids alkaloid NNS 1579 1580 , , , 1581 1591 containing contain VBG 1592 1605 cepharanthine cepharanthine NN 1606 1608 as as IN 1609 1610 a a DT 1611 1616 major major JJ 1617 1626 component component NN 1626 1627 , , , 1628 1631 are be VBP 1632 1638 widely widely RB 1639 1643 used use VBN 1644 1647 for for IN 1648 1651 the the DT 1652 1661 treatment treatment NN 1662 1664 of of IN 1665 1673 patients patient NNS 1674 1678 with with IN 1679 1686 various various JJ 1687 1699 inflammatory inflammatory JJ 1700 1708 diseases disease NNS 1709 1711 in in IN 1712 1717 Japan Japan NNP 1717 1718 , , , 1719 1732 cepharanthine cepharanthine NN 1733 1739 should should MD 1740 1742 be be VB 1743 1750 further further RBR 1751 1758 pursued pursue VBN 1759 1762 for for IN 1763 1766 its its PRP$ 1767 1783 chemotherapeutic chemotherapeutic JJ 1784 1793 potential potential NN 1794 1796 in in IN 1797 1811 HIV-1-infected hiv-1-infected JJ 1812 1820 patients patient NNS 1820 1821 . . .