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

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 μM. For SP-303, stimulated Cl − currents were decreased by 98.0±7.2% and K B 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.