Functional foods and nutrition have become increasingly popular in preventing and reducing the incidence of diabetes. Green coffee bean extract (GCBE) has received much interest because of the evidence that coffee consumption reduces the risk of diabetes and many inflammatory diseases. This study was designed to investigate the phytochemicals contained in GCBE and their antioxidant, anti-diabetic, and anti-inflammatory efficacies. GCBE phytochemicals were analyzed using high-performance liquid chromatography (HPLC). This analysis demonstrated that chlorogenic acid was the predominant component of GCBE, followed by caffeine and caffeic acid. The antioxidant capacity of GCBE was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azinobis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays, demonstrating significant scavenging capacity with IC50 values of 2.96 ± 1.04 and 7.63 ± 1.03 µg/mL, respectively. The anti-hyperlipidemic efficacy of GCBE was observed through inhibiting cholesterol absorption (by increasing micelle sizes and decreasing cholesterol solubility), lipid digestion, and pancreatic lipase activity in vitro. The investigations revealed that GCBE possessed anti-hyperlipidemic properties by inhibiting cholesterol absorption, lipid digestion, and pancreatic lipase activity. Specifically, GCBE increased micelle particle sizes by ~6.5-fold, decreased cholesterol solubility by 2-fold, and reduced pancreatic lipase activity by 25%. Additionally, the in vitroanti-hyperglycemic activity of GCBE was evaluated by inhibition of α-amylase and α-glucosidase capacity. GCBE demonstrated anti-hyperglycemic activity by inhibiting α-amylase activity (32.80 ± 7.06% inhibition), while α-glucosidase activity remained unaffected. The anti-inflammatory potential of GCBE was evaluated by mRNA regulation using RT-PCR analysis. This analysis revealed that GCBE attenuated mRNA expression of COX-2, TNF-α, IL-1b, and IL-6 in LPS-induced RAW264.7 cells. GCBE’s antioxidant, anti-hyperlipidemic, and anti-hyperglycemic efficacies and its molecular mechanisms in modulating the inflammation pathway found in the present study highlight its potential as a supplement in functional foods or beverages. Doi: 10.28991/HEF-2024-05-01-08 Full Text: PDF