1. Structure-function analysis of purified proanthocyanidins reveals a role for polymer size in suppressing inflammatory responses
- Author
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Juha-Pekka Salminen, S.M. Thamsborg, M. M. Leppä, Andrew R. Williams, and Audrey I.S. Andersen-Civil
- Subjects
0301 basic medicine ,endocrine system diseases ,QH301-705.5 ,medicine.medical_treatment ,education ,Anti-Inflammatory Agents ,Medicine (miscellaneous) ,Inflammation ,Mechanism of action ,Degree of polymerization ,General Biochemistry, Genetics and Molecular Biology ,Article ,Transcriptome ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Applied immunology ,health services administration ,medicine ,Animals ,Proanthocyanidins ,Biology (General) ,Plant Extracts ,Chemistry ,Macrophages ,Autophagy ,food and beverages ,Metabolism ,humanities ,Cell biology ,030104 developmental biology ,RAW 264.7 Cells ,Cytokine ,Proanthocyanidin ,030220 oncology & carcinogenesis ,Cytokines ,medicine.symptom ,General Agricultural and Biological Sciences ,Flux (metabolism) - 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., Andersen-Civil et al isolated a range of proanthocyanidin (PAC) polymer mixtures from plant material and demonstrated that polymer size was a key determinant of the ability of PACs to regulate inflammatory responses in murine macrophages, and intestinal tissues following oral intake. The PAC polymers modulated autophagic flux and inhibited lipopolysaccharide-induced autophagy in macrophages, which could help to explain the health benefits of PAC-rich food.
- Published
- 2021
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