Date of Award

Summer 8-2018

Level of Access Assigned by Author

Open-Access Thesis

Degree Name

Master of Science (MS)

Department

Food Science and Human Nutrition

Advisor

Dorothy Klimis-Zacas

Second Committee Member

John D.Lambris

Third Committee Member

Robert Gundersen

Additional Committee Members

Adrienne White

Abstract

Ingestion of berries containing polyphenols is associated with lower risk of inflammatory, metabolic, cardiovascular and degenerative diseases. Diet has been shown to modulate the activation of the complement system, a set of over 50 proteins present in the circulation and tissues that reacts in response to damage or microbial encounter and is critical for the maintenance of homeostasis. Imbalanced activation is tightly correlated with inflammation and various pathologies. Wild blueberries are a rich source of anthocyanins and phenolic acids, which can be found in plasma shortly after consumption. Given the involvement of both complement and polyphenols in the modulation of inflammation, we investigated whether wild blueberries modulate the activation of the complement system. Phenolics (Phen) and Anthocyanins (ACNs)

were extracted from freeze-dried wild blueberry powder, characterized by liquid chromatography and used in in-vitro complement inhibition assays. We documented that Phen and ACNs inhibit the activation of the complement classical pathway in a dose-dependent manner with IC50 of 325.6μg/ml and 605.6μg/ml respectively. The activation of the alternative pathway was not impacted by the bioactives. Phenolic metabolites syringic, protocatechuric, gallic, chlorogenic, and hippuric acids also showed inhibitory activity with an IC50 of approximately, 1mM. Mechanistically, we determined that polyphenols impact specifically the complement classical pathway by targeting the activation of complement protein C4 through the C1s enzyme. This study presents novel data on the inhibition of the complement classical pathway by phenolic compounds extracted from wild blueberries, shedding new light on the anti-inflammatory properties and potential health benefits of berry consumption.

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