A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells

Horst Fischer, Terry E. Machen, Jonathan Widdicombe, Thomas J S Carlson, Steven R. King, John W S Chow, Beate Illek

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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 (KB) of 4.8±0.8 μM. For SP-303, stimulated Cl- currents were decreased by 98.0±7.2% and KB averaged 4.1±1.3 μM. 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 μM 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®) and SB-300 (used in NSF Normal Stool Formula™) 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.

Original languageEnglish (US)
Pages (from-to)351-357
Number of pages7
JournalJournal of Ethnopharmacology
Volume93
Issue number2-3
DOIs
StatePublished - Aug 2004

Keywords

  • Chloride channel blocker
  • Croton lechleri
  • Cystic fibrosis transmembrane conductance regulator chloride channel
  • Diarrhea
  • Dietary supplement
  • Herbal extract
  • Proanthocyanidin

ASJC Scopus subject areas

  • Pharmacology

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