期刊
JOURNAL OF ETHNOPHARMACOLOGY
卷 93, 期 2-3, 页码 351-357出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2004.04.005
关键词
Croton lechleri; proanthocyanidin; herbal extract; dietary supplement; diarrhea; cystic fibrosis transmembrane conductance regulator chloride channel; chloride channel blocker
An oligomeric proanthocyanidin (SP-303) extracted from the bark latex of the tree Croton lechleri (family Euphorbiaceae) is a potent inhibitor of cholera toxin-induced fluid accumulation and chloride secretion. The manufacturing process for SP-303 was optimized and simplified to produce an increased yield of the herbal extract. The novel extract (named SB-300) contained on average 70.6 +/- 7.2% SP-303 by weight (mean +/- S.D.; n = 56 lots). Here, we describe the effectiveness of SB-300 on cAMP-regulated chloride secretion, which is mediated by the cystic fibrosis transmembrane conductance regulator Cl- channel (CFTR) in human colonic T84 cells. Exposure of the apical surface to SB-300 blocked forskolin-stimulated Cl- secretion by 92.2 +/- 3.0% with a half-maximal inhibition constant (K-B) of 4.8 +/- 0.8 muM. For SP-303, stimulated Cl- currents were decreased by 98.0 +/- 7.2% and K-B averaged 4.1 +/- 1.3 muM. There was no significant difference between the blocking kinetics of SP-303 and SB-300. Forskolin-stimulated whole cell Cl- currents were effectively blocked by extracellular addition of SB-300 (63 +/- 8.5%; n = 3) and to a similar extent by SP-303 (83 +/- 0.6%; n = 2; at 50 muM each). Both extracts inhibited a time- and voltage-independent Cl- conductance, which indicated the involvement of CFTR Cl- channels. We conclude that both SP-303 (used in Provir(R)) and SB-300 (used in NSF Normal Stool Formula(TM)) are novel natural products that target the CFTR Cl- channel. SB-300 is a low cost herbal extract and may present a complementary and alternative medicine approach for the treatment of fluid loss in watery diarrhea. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
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