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

49 Citations (Scopus)

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

Fingerprint

Croton
Latex
Chlorides
Epithelial Cells
Colforsin
Complementary Therapies
Plant Bark
Euphorbiaceae
Cystic Fibrosis Transmembrane Conductance Regulator
Cholera Toxin
SP 303
Biological Products
Diarrhea
Weights and Measures
Costs and Cost Analysis

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells. / Fischer, Horst; Machen, Terry E.; Widdicombe, Jonathan; Carlson, Thomas J S; King, Steven R.; Chow, John W S; Illek, Beate.

In: Journal of Ethnopharmacology, Vol. 93, No. 2-3, 08.2004, p. 351-357.

Research output: Contribution to journalArticle

Fischer, Horst ; Machen, Terry E. ; Widdicombe, Jonathan ; Carlson, Thomas J S ; King, Steven R. ; Chow, John W S ; Illek, Beate. / A novel extract SB-300 from the stem bark latex of Croton lechleri inhibits CFTR-mediated chloride secretion in human colonic epithelial cells. In: Journal of Ethnopharmacology. 2004 ; Vol. 93, No. 2-3. pp. 351-357.
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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{\circledR}) 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.",
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