Coffeeberry Activates the CaMKII/CREB/BDNF Pathway, Normalizes Autophagy and Apoptosis Signaling in Nonalcoholic Fatty Liver Rodent Model

• Published in: Nutrients 2021-10, Vol.13 (10), p.3652
• Main Authors: Lu, Meng-Chun, Lee, I-Te, Hong, Ling-Zong, Ben-Arie, Eyal, Lin, Yu-Hsuan, Lin, Wei-Ting, Kao, Pei-Yu, Yang, Mei-Due, Chan, Yin-Ching
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis-inducing factor; Autophagy; Brain-derived neurotrophic factor; Ca2+/calmodulin-dependent protein kinase II; Calcium ions; Calcium-binding protein; Calmodulin; CaMKII/CREB/BDNF; Carbonyl compounds; Carbonyls; coffeeberry; Cyclic AMP response element-binding protein; Diet; Fatty liver; Hepatocytes; Kinases; Lipid peroxidation; Lipids; Liver; Liver diseases; Malondialdehyde; Metabolism; nonalcoholic fatty liver disease; Nutrition research; Oxidation; Oxidative stress; Phagocytosis; Proteins; Rapamycin; redox status; Ribose; Rodents; Senescence; Signal transduction; TOR protein
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13103652

Nonalcoholic fatty liver disease (NAFLD) shows extensive liver cell destruction with lipid accumulation, which is frequently accompanied by metabolic comorbidities and increases mortality. This study aimed to investigate the effects of coffeeberry (CB) on regulating the redox status, the CaMKII/CREB/BDNF pathway, autophagy, and apoptosis signaling by a NAFLD rodent model senescence-accelerated mice prone 8 (SAMP8). Three-month-old male SAMP8 mice were divided into a control group and three CB groups (50, 100, and 200 mg/kg BW), and fed for 12 weeks. The results show that CB reduced hepatic malondialdehyde and carbonyl protein levels. CB significantly enhanced Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) and reduced the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio. In addition, CB increased the silent information regulator T1 level, promoted Beclin 1 and microtubule-associated protein light chain 3 II expressions, and reduced phosphorylated mammalian target of rapamycin and its downstream p-p70s6k levels. CB also inhibited the expressions of apoptosis-related factors poly (ADP-ribose) polymerase-1 and the apoptosis-inducing factor. In conclusion, CB might protect the liver by reducing oxidative stress, activating the CaMKII/CREB/BDNF pathway, and improving autophagic and apoptotic expressions in a dose-dependent manner.