MS Thesis Defense by Elena De Pra, "Phytochemical Characterization, Antioxidant Interactions, and Acetylcholinesterase Inhibitory Activities of Cranberry Polyphenol Fractions"
VRB 210
Heather Blaser
508-999-8587
hblaser@umassd.edu
Title: Phytochemical Characterization, Antioxidant Interactions, and Acetylcholinesterase Inhibitory Activities of Cranberry Polyphenol Fractions
Advisor: Dr. Catherine Neto, Chemistry & Biochemistry Dept.
Committee Members: Dr. Shuowei Cai, Chemistry & Biochemistry Dept.; Dr. Brian Blanchette, Chemistry & Biochemistry Dept.
ABSTRACT
Cranberries (Vaccinium macrocarpon) are polyphenol-rich fruits containing diverse bioactive compounds that possess antioxidant properties that can target a variety of biological outcomes. Although synergistic interactions have been widely reported in multi-herb formulas, little is known about the interactions among isolated cranberry polyphenolic fractions. The present study aimed to investigate the phytochemical composition, antioxidant activity, synergistic interactions, and acetylcholinesterase inhibitory potential of polyphenol-enriched fractions isolated from Early Black (EB) and Mullica Queen (MQ) cranberry cultivars. Crude cranberry extracts were fractionated using Diaion HP-20 and Sephadex LH-20 chromatography to isolate phytochemically distinct fractions which were characterized by high-performance liquid chromatography with diode array detection (HPLC-DAD), while selected proanthocyanidin (PAC)-rich fractions were further characterized by matrix-assisted laser desorption-ionization-time-of-flight mass spectrometry (MALDI-TOF MS).
Antioxidant activities were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azionbis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing power (FRAP) assays. Fractions rich in flavonol glycosides and proanthocyanidins showed the most promising activity and were tested independently and as binary combinations (1:1, 2:1, and 1:2) to evaluate their combined effects. These combinations were examined using both a single-concentration effect-based model and a dose-response Combination Index (CI) analysis to determine synergistic, additive, or antagonistic interactions. The effect-based model identified synergistic behavior between flavonol glycoside and PAC-rich fractions as well as between phenolic acid/ anthocyanin-rich fractions and PAC-rich fractions with relative reducing power (RRP) values ranging from 1.01-1.56, whereas radical scavenging activity (RSA) of the mixtures were considered mainly antagonistic with values ranging from 0.67-1.13. The second model instead suggested that most binary combinations exhibited mainly additive effects across all antioxidant assays except for a 1:1 combination of MQ A I + M IV, which showed moderate synergistic activity for scavenging ABTS (CI = 0.57). Selected fractions were also evaluated for acetylcholinesterase inhibitory activity, with the PAC-enriched fraction, MQ A I, exhibiting the greatest inhibitory activity against acetylcholinesterase with an IC50 value of 21.1 mg/mL. Results of this study demonstrate that antioxidant interactions among isolated cranberry polyphenol fractions depends on phytochemical composition, mixing ratio, and mechanism tested. Understanding and exploiting these interactions may enhance their biological advantage while optimizing the bioactive compounds required to achieve desired effects.