Fractionation and biological evaluation of passion fruit Pectins: HG and RG-I backbone ratios are associated with TLR2-1 interaction and signaling.

Lucas de Freitas Pedrosa, Witor Ribeiro Ferraz, Dimitrios Kouzounis, Krishna Desai, Gustavo Henrique Goulart Trossini, Henk A Schols, Paul de Vos, João Paulo Fabi

Journal: Carbohydrate polymers 2025;368(Pt 1):124085

PMID: 40912767

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Abstract

Passion fruit mesocarp is rich in pectin, and high-temperature/pressure modification of this pectin has been shown to yield bioactive fragments with anticancer potential. To clarify the structure-function relationship of passion fruit pectins, we purified native and modified pectins using two fractionation methods. Comprehensive chemical characterization revealed molecular weight as the primary difference between fractions, along with varying proportions of homogalacturonan (HG) and rhamnogalacturonan-I (RG-I). All samples activated TLR2, such as specific agonists (Pam3CSK4, HKLM, FSL-1). Notably, only native and lower-molecular-weight fractions inhibited TLR2/1 activation by the specific agonist Pam3CSK4. Higher methyl esterification correlated with TLR2/1 inhibition at lower doses, whereas RG-I content showed a negative correlation; however, the galacturonic acid-to-rhamnose ratio positively influenced heterodimer inhibition. A highly methyl esterified galacturonic acid heptamer demonstrated a strong affinity for the TLR2/1 binding pocket, as evidenced by molecular dynamics simulations. This study elucidates how modified passion fruit pectin structures interact with TLR2, reinforcing the link between plant polysaccharides and human immune responses.

Address: Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713, GZ, Groningen, the Netherlands; Laboratory of Food Chemistry, Wageningen University & Research, Bornse Weilanden 9, 6708, WG, Wageningen, the Netherlands. Electronic address: [email protected].; Laboratory for the integration of Experimental and Computational Techniques, Department of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900, Brazil. Electronic address: [email protected].; Laboratory of Food Chemistry, Wageningen University & Research, Bornse Weilanden 9, 6708, WG, Wageningen, the Netherlands. Electronic address: [email protected].; Laboratory of Food Chemistry, Wageningen University & Research, Bornse Weilanden 9, 6708, WG, Wageningen, the Netherlands. Electronic address: [email protected].; Laboratory for the integration of Experimental and Computational Techniques, Department of Pharmacy, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-900, Brazil. Electronic address: [email protected].; Laboratory of Food Chemistry, Wageningen University & Research, Bornse Weilanden 9, 6708, WG, Wageningen, the Netherlands. Electronic address: [email protected].; Centre for Healthy Eating & Food Innovation (HEFI), Maastricht University - Campus Venlo, 5928, SZ, Venlo, the Netherlands. Electronic address: [email protected].; Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil; Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo 05508-000, SP, Brazil; Food Research Center (FoRC), CEPID-FAPESP (Research, Innovation and Dissemination Centers, São Paulo Research Foundation), CEPIX-USP, São Paulo 05508-080, SP, Brazil. Electronic address: [email protected].

DOI: 10.1016/j.carbpol.2025.124085

MeSH Terms: Pectins, Passiflora, Toll-Like Receptor 2, Humans, Fruit, Signal Transduction, Molecular Dynamics Simulation, Hexuronic Acids