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

J Ethnopharmacol. 2004 Aug;93(2-3):351-7. doi: 10.1016/j.jep.2004.04.005.


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 microM. For SP-303, stimulated Cl- currents were decreased by 98.0+/-7.2 % and KB averaged 4.1+/-1.3 microM. 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 microM 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chloride Channels / drug effects*
  • Chlorides / metabolism*
  • Colon / cytology
  • Colon / drug effects*
  • Croton*
  • Cystic Fibrosis Transmembrane Conductance Regulator / drug effects
  • Epithelial Cells / drug effects
  • Humans
  • Patch-Clamp Techniques
  • Phytotherapy*
  • Plant Bark
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use


  • CFTR protein, human
  • Chloride Channels
  • Chlorides
  • Plant Extracts
  • Cystic Fibrosis Transmembrane Conductance Regulator