Structure-function analysis of purified proanthocyanidins reveals a role for polymer size in suppressing inflammatory responses
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Structure-function analysis of purified proanthocyanidins reveals a role for polymer size in suppressing inflammatory responses. / Andersen-Civil, Audrey Inge Schytz; Leppä, Milla Marleena; Thamsborg, Stig M.; Salminen, Juha Pekka; Williams, Andrew R.
In: Communications Biology , Vol. 4, 896, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Structure-function analysis of purified proanthocyanidins reveals a role for polymer size in suppressing inflammatory responses
AU - Andersen-Civil, Audrey Inge Schytz
AU - Leppä, Milla Marleena
AU - Thamsborg, Stig M.
AU - Salminen, Juha Pekka
AU - Williams, Andrew R.
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1038/s42003-021-02408-3
DO - 10.1038/s42003-021-02408-3
M3 - Journal article
C2 - 34290357
AN - SCOPUS:85110943107
VL - 4
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
M1 - 896
ER -
ID: 275825804