Antiprotozoal effect of saponins in the rumen can be enhanced by chemical modifications in their structure

Eva Ramos-Morales, Gabriel de la Fuente, Stephane Duval, Christof Wehrli, Marc Bouillon, Martina Lahmann, David Preskett, Radek Braganca, Charles J Newbold

Research output: Contribution to journalArticle

6 Citations (Scopus)
6 Downloads (Pure)

Abstract

The antiprotozoal effect of saponins is transitory, as when saponins are deglycosylated to the sapogenin by rumen microorganisms they become inactive. We postulated that the substitution of the sugar moiety of the saponin with small polar residues would produce sapogen-like analogs which might be resistant to degradation in the rumen as they would not be enzymatically cleaved, allowing the antiprotozoal effect to persist over time. In this study, we used an acute assay based on the ability of protozoa to break down [14C] leucine-labeled Streptococcus bovis and a longer term assay based on protozoal motility over 24 h to evaluate both the antiprotozoal effect and the stability of this effect with fifteen hederagenin bis-esters esterified with two identical groups, and five cholesterol and cholic acid based derivatives carrying one to three succinate residues. The acute antiprotozoal effect of hederagenin derivatives was more pronounced than that of cholesterol and cholic acid derivatives. Modifications in the structure of hederagenin, cholesterol, and cholic acid derivatives resulted in compounds with different biological activities in terms of acute effect and stability, although those which were highly toxic to protozoa were not always the most stable over time. Most of the hederagenin bis-esters, and in particular hederagenin bis-succinate (TSB24), hederagenin bis-betainate dichloride (TSB37) and hederagenin bis-adipate (TSB47) had a persistent effect against rumen protozoa in vitro, shifting the fermentation pattern toward higher propionate and lower butyrate. These chemically modified triterpenes could potentially be used in ruminant diets as an effective defaunation agent to, ultimately, increase nitrogen utilization, decrease methane emissions, and enhance animal production. Further trials in vivo or in long term rumen simulators are now needed to confirm the in vitro observations presented.

Original languageEnglish
Article number399
JournalFrontiers in Microbiology
Volume8
Early online date16 Mar 2017
DOIs
Publication statusFirst published - 16 Mar 2017
Externally publishedYes

Fingerprint

Rumen
Saponins
Cholic Acid
Cholesterol
Succinic Acid
Esters
Sapogenins
Streptococcus bovis
Triterpenes
Butyrates
Poisons
Methane
Propionates
Ruminants
hederagenin
Leucine
Fermentation
Nitrogen
Diet

Cite this

Ramos-Morales, Eva ; de la Fuente, Gabriel ; Duval, Stephane ; Wehrli, Christof ; Bouillon, Marc ; Lahmann, Martina ; Preskett, David ; Braganca, Radek ; Newbold, Charles J. / Antiprotozoal effect of saponins in the rumen can be enhanced by chemical modifications in their structure. In: Frontiers in Microbiology. 2017 ; Vol. 8.
@article{f4b040d1b764418aa9618eed2b292745,
title = "Antiprotozoal effect of saponins in the rumen can be enhanced by chemical modifications in their structure",
abstract = "The antiprotozoal effect of saponins is transitory, as when saponins are deglycosylated to the sapogenin by rumen microorganisms they become inactive. We postulated that the substitution of the sugar moiety of the saponin with small polar residues would produce sapogen-like analogs which might be resistant to degradation in the rumen as they would not be enzymatically cleaved, allowing the antiprotozoal effect to persist over time. In this study, we used an acute assay based on the ability of protozoa to break down [14C] leucine-labeled Streptococcus bovis and a longer term assay based on protozoal motility over 24 h to evaluate both the antiprotozoal effect and the stability of this effect with fifteen hederagenin bis-esters esterified with two identical groups, and five cholesterol and cholic acid based derivatives carrying one to three succinate residues. The acute antiprotozoal effect of hederagenin derivatives was more pronounced than that of cholesterol and cholic acid derivatives. Modifications in the structure of hederagenin, cholesterol, and cholic acid derivatives resulted in compounds with different biological activities in terms of acute effect and stability, although those which were highly toxic to protozoa were not always the most stable over time. Most of the hederagenin bis-esters, and in particular hederagenin bis-succinate (TSB24), hederagenin bis-betainate dichloride (TSB37) and hederagenin bis-adipate (TSB47) had a persistent effect against rumen protozoa in vitro, shifting the fermentation pattern toward higher propionate and lower butyrate. These chemically modified triterpenes could potentially be used in ruminant diets as an effective defaunation agent to, ultimately, increase nitrogen utilization, decrease methane emissions, and enhance animal production. Further trials in vivo or in long term rumen simulators are now needed to confirm the in vitro observations presented.",
author = "Eva Ramos-Morales and {de la Fuente}, Gabriel and Stephane Duval and Christof Wehrli and Marc Bouillon and Martina Lahmann and David Preskett and Radek Braganca and Newbold, {Charles J}",
year = "2017",
month = "3",
day = "16",
doi = "10.3389/fmicb.2017.00399",
language = "English",
volume = "8",
journal = "Frontiers in Microbiology",
issn = "1664-302X",
publisher = "Frontiers Media",

}

Antiprotozoal effect of saponins in the rumen can be enhanced by chemical modifications in their structure. / Ramos-Morales, Eva; de la Fuente, Gabriel; Duval, Stephane; Wehrli, Christof; Bouillon, Marc; Lahmann, Martina; Preskett, David; Braganca, Radek; Newbold, Charles J.

In: Frontiers in Microbiology, Vol. 8, 399, 16.03.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antiprotozoal effect of saponins in the rumen can be enhanced by chemical modifications in their structure

AU - Ramos-Morales, Eva

AU - de la Fuente, Gabriel

AU - Duval, Stephane

AU - Wehrli, Christof

AU - Bouillon, Marc

AU - Lahmann, Martina

AU - Preskett, David

AU - Braganca, Radek

AU - Newbold, Charles J

PY - 2017/3/16

Y1 - 2017/3/16

N2 - The antiprotozoal effect of saponins is transitory, as when saponins are deglycosylated to the sapogenin by rumen microorganisms they become inactive. We postulated that the substitution of the sugar moiety of the saponin with small polar residues would produce sapogen-like analogs which might be resistant to degradation in the rumen as they would not be enzymatically cleaved, allowing the antiprotozoal effect to persist over time. In this study, we used an acute assay based on the ability of protozoa to break down [14C] leucine-labeled Streptococcus bovis and a longer term assay based on protozoal motility over 24 h to evaluate both the antiprotozoal effect and the stability of this effect with fifteen hederagenin bis-esters esterified with two identical groups, and five cholesterol and cholic acid based derivatives carrying one to three succinate residues. The acute antiprotozoal effect of hederagenin derivatives was more pronounced than that of cholesterol and cholic acid derivatives. Modifications in the structure of hederagenin, cholesterol, and cholic acid derivatives resulted in compounds with different biological activities in terms of acute effect and stability, although those which were highly toxic to protozoa were not always the most stable over time. Most of the hederagenin bis-esters, and in particular hederagenin bis-succinate (TSB24), hederagenin bis-betainate dichloride (TSB37) and hederagenin bis-adipate (TSB47) had a persistent effect against rumen protozoa in vitro, shifting the fermentation pattern toward higher propionate and lower butyrate. These chemically modified triterpenes could potentially be used in ruminant diets as an effective defaunation agent to, ultimately, increase nitrogen utilization, decrease methane emissions, and enhance animal production. Further trials in vivo or in long term rumen simulators are now needed to confirm the in vitro observations presented.

AB - The antiprotozoal effect of saponins is transitory, as when saponins are deglycosylated to the sapogenin by rumen microorganisms they become inactive. We postulated that the substitution of the sugar moiety of the saponin with small polar residues would produce sapogen-like analogs which might be resistant to degradation in the rumen as they would not be enzymatically cleaved, allowing the antiprotozoal effect to persist over time. In this study, we used an acute assay based on the ability of protozoa to break down [14C] leucine-labeled Streptococcus bovis and a longer term assay based on protozoal motility over 24 h to evaluate both the antiprotozoal effect and the stability of this effect with fifteen hederagenin bis-esters esterified with two identical groups, and five cholesterol and cholic acid based derivatives carrying one to three succinate residues. The acute antiprotozoal effect of hederagenin derivatives was more pronounced than that of cholesterol and cholic acid derivatives. Modifications in the structure of hederagenin, cholesterol, and cholic acid derivatives resulted in compounds with different biological activities in terms of acute effect and stability, although those which were highly toxic to protozoa were not always the most stable over time. Most of the hederagenin bis-esters, and in particular hederagenin bis-succinate (TSB24), hederagenin bis-betainate dichloride (TSB37) and hederagenin bis-adipate (TSB47) had a persistent effect against rumen protozoa in vitro, shifting the fermentation pattern toward higher propionate and lower butyrate. These chemically modified triterpenes could potentially be used in ruminant diets as an effective defaunation agent to, ultimately, increase nitrogen utilization, decrease methane emissions, and enhance animal production. Further trials in vivo or in long term rumen simulators are now needed to confirm the in vitro observations presented.

U2 - 10.3389/fmicb.2017.00399

DO - 10.3389/fmicb.2017.00399

M3 - Article

C2 - 28382023

VL - 8

JO - Frontiers in Microbiology

JF - Frontiers in Microbiology

SN - 1664-302X

M1 - 399

ER -