A1 Refereed original research article in a scientific journal

Structure-function analysis of purified proanthocyanidins reveals a role for polymer size in suppressing inflammatory responses




AuthorsAndersen-Civil Audrey Inge Schytz, Leppä Milla Marleena, Thamsborg Stig M., Salminen Juha-Pekka, Williams Andrew R.

PublisherNATURE RESEARCH

Publication year2021

JournalCommunications Biology

Journal name in sourceCOMMUNICATIONS BIOLOGY

Journal acronymCOMMUN BIOL

Article numberARTN 896

Volume4

Number of pages14

eISSN2399-3642

DOIhttps://doi.org/10.1038/s42003-021-02408-3

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/66540362


Abstract
Proanthocyanidins (PAC) are dietary compounds that have been extensively studied for beneficial health effects due to their anti-inflammatory properties. However, the structure-function relationships of PAC and their mode-of-action remain obscure. Here, we isolated a wide range of diverse PAC polymer mixtures of high purity from plant material. Polymer size was a key factor in determining the ability of PAC to regulate inflammatory cytokine responses in murine macrophages. PAC polymers with a medium (9.1) mean degree of polymerization (mDP) induced substantial transcriptomic changes, whereas PAC with either low (2.6) or high (12.3) mDP were significantly less active. Short-term oral treatment of mice with PAC modulated gene pathways connected to nutrient metabolism and inflammation in ileal tissue in a polymerization-dependent manner. Mechanistically, the bioactive PAC polymers modulated autophagic flux and inhibited lipopolysaccharide-induced autophagy in macrophages. Collectively, our results highlight the importance of defined structural features in the health-promoting effects of PAC-rich foods.

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