TY - JOUR
T1 - Triterpene glycosides from Blighia welwitschii and evaluation of their antibody recognition capacity in multiple sclerosis
AU - Petit, Bastien
AU - Mitaine-Offer, Anne Claire
AU - Fernández, Feliciana Real
AU - Papini, Anna Maria
AU - Delaude, Clément
AU - Miyamoto, Tomofumi
AU - Tanaka, Chiaki
AU - Rovero, Paolo
AU - Lacaille-Dubois, Marie Aleth
N1 - Funding Information:
From a structural point of view, compounds 6, 7 and hederagenin monodesmoside exhibited a similar five-residue oligosaccharide at C-3 of their agylcone, as well as an additional Glc disaccharide at C-28 for 6 and 7 (see Fig. 1). Despite the occurrence of a terminal Glc, a high antibody recognition pattern, for 6 and 7, their antibody recognition capacity was comparable to hederagenin monodesmoside, exhibiting no terminal Glc, suggesting that long sugar chains at C-3 of 6 and 7 might impair antibody binding (see Fig. 2). This result tends to corroborate hypotheses formulated in previous studies, in which saponins exhibiting long sugar chains, demonstrated a poor capacity to recognize Abs in MS (Peroni et al., 2016; Champy-Tixier et al., 2018). More importantly, similar findings have been reached by peers using a totally different ELISA system, characterized by various glycan antigens covalently linked to BSA, which tend to support our ELISA model using natural glycosides (Braganza et al., 2018).This research work was financially supported by grants from the French Government (French Ministry of Higher Education, Research and Innovation), the doctoral school n?554 ?Environnements-Sant?? of the University of Burgundy and Franche-Comt? and the AromaPro association. Dominic Batt, English teacher at the University of Burgundy and Franche-Comt?, is gratefully acknowledged for his revision of the manuscript.
Funding Information:
This research work was financially supported by grants from the French Government (French Ministry of Higher Education, Research and Innovation ), the doctoral school n°554 “Environnements-Santé” of the University of Burgundy and Franche-Comté and the AromaPro association. Dominic Batt, English teacher at the University of Burgundy and Franche-Comté, is gratefully acknowledged for his revision of the manuscript.
Publisher Copyright:
© 2020
PY - 2020/8
Y1 - 2020/8
N2 - Multiple sclerosis (MS) in a multifactorial autoimmune disease in which reliable biomarkers are needed for therapeutic monitoring and diagnosis. Autoantibodies (autoAbs) are known biomarker candidates although their detection in biological fluids requires a thorough characterization of their associated antigens. Over the past twenty years, a reverse chemical-based approach aiming to screen putative autoantigens has underlined the role of glycans, in particular glucose, in MS. Despite the progress achieved, a lack of consensus regarding the nature of innate antigens as well as difficulties proposing new synthetic glucose-based structures have proved to be obstacles. Here is proposed a strategy to extend the current methodology to the field of natural glycosides, in order to dramatically increase the diversity of glycans that could be tested. Triterpene saponins from the Sapindaceace family represent an optimal starting material as their abundant description in the literature has revealed a prevalence of glucose-based oligosaccharides. Blighia welwitschii (Sapindaceae) was thus selected as a case study and twelve triterpene saponins were isolated and characterized. Their structures were elucidated on the basis of 1D and 2D NMR as well as mass spectrometry, revealing seven undescribed compounds. A selection of natural glycosides exhibiting various oligosaccharide moieties were then tested as antigens in enzyme-linked immunosorbent assay (ELISA) to recognize IgM antibodies (Abs) in MS patients’ sera. Immunoassay results indicated a correlation between the glycan structures and their antibody recognition capacity, allowing the determination of structure-activity relationships that were coherent with previous studies. This approach might help to identify sugar epitopes putatively involved in MS pathogenesis, which remains poorly understood.
AB - Multiple sclerosis (MS) in a multifactorial autoimmune disease in which reliable biomarkers are needed for therapeutic monitoring and diagnosis. Autoantibodies (autoAbs) are known biomarker candidates although their detection in biological fluids requires a thorough characterization of their associated antigens. Over the past twenty years, a reverse chemical-based approach aiming to screen putative autoantigens has underlined the role of glycans, in particular glucose, in MS. Despite the progress achieved, a lack of consensus regarding the nature of innate antigens as well as difficulties proposing new synthetic glucose-based structures have proved to be obstacles. Here is proposed a strategy to extend the current methodology to the field of natural glycosides, in order to dramatically increase the diversity of glycans that could be tested. Triterpene saponins from the Sapindaceace family represent an optimal starting material as their abundant description in the literature has revealed a prevalence of glucose-based oligosaccharides. Blighia welwitschii (Sapindaceae) was thus selected as a case study and twelve triterpene saponins were isolated and characterized. Their structures were elucidated on the basis of 1D and 2D NMR as well as mass spectrometry, revealing seven undescribed compounds. A selection of natural glycosides exhibiting various oligosaccharide moieties were then tested as antigens in enzyme-linked immunosorbent assay (ELISA) to recognize IgM antibodies (Abs) in MS patients’ sera. Immunoassay results indicated a correlation between the glycan structures and their antibody recognition capacity, allowing the determination of structure-activity relationships that were coherent with previous studies. This approach might help to identify sugar epitopes putatively involved in MS pathogenesis, which remains poorly understood.
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U2 - 10.1016/j.phytochem.2020.112392
DO - 10.1016/j.phytochem.2020.112392
M3 - Article
C2 - 32512361
AN - SCOPUS:85085767757
VL - 176
JO - Phytochemistry
JF - Phytochemistry
SN - 0031-9422
M1 - 112392
ER -