Validating the Health Benefits of Coffee Berry Pulp Extracts in Mice with High-Fat Diet-Induced Obesity and Diabetes

Abstract

The effects of coffee (Coffea arabica L.) berry pulp extracts (CBP extracts) on the improvement of diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD) were evaluated using various in vitro antioxidant activity assays and through a high-fat diet-induced mild diabetic obese mouse model. After an 84-day oral administration of CBP extracts (400-100 mg/kg), bioactivities were evaluated. The in vitro analysis showed the highest DPPH^● scavenging activity of 73.10 ± 4.27%, ABTS^● scavenging activity of 41.18 ± 1.14%, and SOD activity of 56.24 ± 2.81%, at a CBP extract concentration of 1000 µg/mL. The in vivo analysis of the CBP extracts showed favorable and dose-dependent anti-obesity, anti-diabetic, NAFLD, nephropathy, and hyperlipidemia refinement effects through hepatic glucose enzyme activity, 5'-AMP-activated protein kinase (AMPK) up-regulation, antioxidant activity, lipid metabolism-related gene expression, and pancreatic lipid digestion enzyme modulatory activities. This study shows that an appropriate oral dosage of CBP extracts could function as a potent herbal formulation for a refinement agent or medicinal food ingredient to control type 2 diabetes and related complications.

Keywords: Coffea arabica L.; antioxidant; coffee berry pulp; diabetic obese mice; high-fat-diet; type 2 diabetes.

Figure 1

Antioxidant activity of CBP extracts. (A) DPPH-radical scavenging activity, (B) ABTS-radical scavenging activity, and (C) SOD activity of CBP extracts at different concentrations ranging from 0 to 1000 µg/mL; C: Control (L-ascorbic acid was used as a control treatment); CBP: Coffee berry pulp extracts.

Figure 2

Body weight gains in mice supplied with either NFD or HFD. Values are expressed as means ± S.D. of 10 mice; NFD: Normal pellet diet; HFD: 45% Kcal high-fat diet; CBP: Coffee berry pulp extracts; THSD: Tukey’s Honest Significant Difference; DT3: Dunnett’s T3; NFD control: Vehicle (10 mL/kg distilled water) orally administered mice with NFD supply; HFD control: Vehicle (10 mL/kg distilled water) orally administered mice with HFD supply; ^a p < 0.01 as compared with NFD control by THSD test; ^b p < 0.01 as compared with NFD control by DT3 test; ^c p < 0.01 as compared with the HFD control using the DT3 test.

Figure 3

Representative general histological images of the pancreas, taken from mice supplied with either NFD or HFD. (A) Vehicle (10 mL/kg distilled water) orally administered mice with NFD supply (NFD control); (B) Vehicle (10 mL/kg distilled water) orally administered mice with HFD supply (HFD control); (C) Metformin (250 mg/kg) orally administered mice with HFD supply (MET₂₅₀); (D) CBP (400 mg/kg) orally administered mice with HFD supply (CBP₄₀₀); (E) CBP (200 mg/kg) orally administered mice with HFD supply (CBP₂₀₀); (F) CBP (100 mg/kg) orally administered mice with HFD supply (CBP₁₀₀); NFD: Normal pellet diet; HFD: 45% Kcal high-fat diet; CBP: Coffee berry pulp extracts; IS: Pancreatic islet; PD: Pancreatic secretory duct; All hematoxylin and eosin stained; Scale bars: 80 µm.

Figure 4

Serum insulin and blood HbA1c content in mice supplied with either NFD or HFD. Values are expressed as mean ± S.D. of 10 mice; NFD: Normal pellet diet; HFD: 45% Kcal high-fat diet; CBP: Coffee berry pulp extracts; HbA1c: Glycated hemoglobin—hemoglobin A1c; THSD: Tukey’s Honest Significant Difference; NFD control: Vehicle (10 mL/kg distilled water) orally administered mice with NFD supply; HFD control: Vehicle (10 mL/kg distilled water) orally administered mice with HFD supply; ^a p < 0.01 as compared with the NFD control using the THSD test; ^b p < 0.01 as compared with the HFD control using the THSD test.

Figure 5

Representative histological images of the insulin- and glucagon-immunoreactive cells in the pancreas, taken from mice supplied with either NFD or HFD. (A): Vehicle (10 mL/kg distilled water) orally administered mice with NFD supply (NFD control); (B): Vehicle (10 mL/kg distilled water) orally administered mice with HFD supply (HFD control); (C): Metformin (250 mg/kg) orally administered mice with HFD supply (MET₂₅₀); (D): CBP (400 mg/kg) orally administered mice with HFD supply (CBP₄₀₀); (E): CBP (200 mg/kg) orally administered mice with HFD supply (CBP₂₀₀); (F): CBP (100 mg/kg) orally administered mice with HFD supply (CBP₁₀₀); NFD: Normal pellet diet; HFD: 45% Kcal high-fat diet; CBP: Coffee berry pulp extracts; IS: Pancreatic islet; PD: Pancreatic secretory duct; All samples were immunostained by avidin–biotin–peroxidase complex; Scale bars: 80 µm.

Figure 6

Fecal TC and TG content in mice supplied with either NFD or HFD. Values are expressed as mean ± S.D. of 10 mice; NFD: Normal pellet diet; HFD: 45% Kcal high-fat diet; CBP: Coffee berry pulp extracts; TC: Total cholesterol; TG: Triglyceride; THSD: Tukey’s Honest Significant Difference; NFD control: Vehicle (10 mL/kg distilled water) orally administered mice with NFD supply; HFD control: Vehicle (10 mL/kg distilled water) orally administered mice with HFD supply; ^a p < 0.01 as compared with the NFD control using the THSD test; ^b p < 0.01 as compared with the HFD control using the THSD test.