Inhibition of Escherichia coli heat-labile enterotoxin-induced diarrhea by Chaenomeles speciosa.
Enterotoxigenic Escherichia coli (ETEC) is responsible for millions of deaths in developing countries. Heat-labile enterotoxin (LT), the virulence factor of ETEC, induces diarrhea by initially binding to the G(M1) on the surface of intestinal epithelial cells and consequently leading to the massive loss of fluid and ions from cells. Fruit of Chaenomeles (FC), the dried fruit of Chaenomeles speciosa, has been used for diarrhea in China. However, the anti-diarrheal mechanism of FC is still unclear. In this study, we demonstrated that FC extract (FCE) inhibited the LT-induced diarrhea in mice by blocking the binding of the B subunit of LT (LTB) to G(M1). The ethyl acetate (EA) soluble fraction was the most active fraction of FC that significantly abolished the LTB and G(M1) interaction. Furthermore, the oleanolic acid, ursolic acid, and betulinic acid from EA fraction, blocked the toxin binding effects, resulting in the suppression of LT-induced diarrhea. Moreover, by docking techniques, these compounds fitted LTB well via hydrogen bonds and hydrophobic contacts with amino acid residues of LTB. In conclusion, our findings suggested that oleanolic acid, ursolic acid, and betulinic acid were the active constituents from FC and might be considered as lead therapeutic agents in the treatment of LT-induced diarrhea.
Chen
Jaw-Chyun
JC
Graduate Institute of Chinese Pharmaceutical Sciences, China Medical University, Taichung, Taiwan.
Chang
Yuan-Shiun
YS
Wu
Shih-Lu
SL
Chao
De-Cheng
DC
Chang
Chih-Shiang
CS
Li
Chia-Cheng
CC
Ho
Tin-Yun
TY
Hsiang
Chien-Yun
CY
D020001:1-Butanol / Q000737:chemistry; D000085:Acetates / Q000737:chemistry; D000818:Animals; D000930:Antidiarrheals / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000378:metabolism / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005638:Fruit / Q000737:chemistry; D007075:Immunoglobulin M / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D027824:Rosaceae / Q000737:chemistry*; D014315:Triterpenes / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D000094062:Betulinic Acid; D000097245:Ursolic Acid
D020001:1-Butanol; D000085:Acetates; D000930:Antidiarrheals; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007075:Immunoglobulin M; D009828:Oleanolic Acid; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D021122:Protein Subunits; D014315:Triterpenes; D000094062:Betulinic Acid; D000097245:Ursolic Acid; C007650:ethyl acetate; C027538:heat-labile enterotoxin, E coli