Dietary Ficus carica Inhibits Cognitive Impairment in Hypoxia-induced Non-alcoholic Fatty Liver Disease

Abstract

Intermittent hypoxia (IH) can aggravate non-alcoholic fatty liver disease (NAFLD) by activating hypoxia-inducible Factor-α and increasing oxidative stress. Lipid peroxidation, which occurs as a consequence of reactive oxygen species (ROS) generation, is characterized by malondialdehyde (MDA) formation and decreased catalase (CAT) and superoxide dismutase (SOD) levels. Hence, inadequate management of NAFLD might induce cognitive impairment. However, although studies have shown that Ficus carica could prevent cognitive impairment due to NAFLD complications, the mechanism by which this is achieved remains unclear. The current study therefore aimed to clarify the effects of Ficus carica in suppressing cognitive impairments caused by hypoxia-induced NAFLD. Sprague-Dawley male rats were divided into five groups: negative control positive control (PC), and IH with Ficus carica treatment (6.25, 12.5, and 25 mL/kg/day) for 4 weeks before and 1 week during IH. Rats were exposed to IH exposure by placing them in a hypoxic chamber (90% N₂ and 10% O₂) for 7 days. Regardless of dosage, Ficus carica treatment reduced MDA levels when compared to PC, and low-dose increased liver SOD levels more than the other groups. In contrast, the medium Ficus carica dose was associated with increased CAT activity and decreased inflammatory marker levels compared to the other treatments. Meanwhile, the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index were all greatest in the medium-dose group. The PC group showed a significant decrease in the percentage of alteration. Our data implies that medium doses of Ficus carica can reduce cognitive impairment caused by hypoxia-induced NAFLD.

Keywords: Antioxidant; Cognitive impairment; Ficus carica; Hypoxia; Non-alcoholic fatty liver disease.

Figure 1

Experimental protocol

Figure 2

Effect of whole Ficus carica on HIF1-α in plasma and brain *p < 0.05 compared to pre and post (A). Different letters (a,b,c) in the same column indicate a significant difference between groups according to the one-way ANOVA (p < 0.05) and Duncan post-hoc test.

Figure 3

Effect of whole Ficus carica on anti-inflammatory as NAFLD parameters Lym, Lymphocyte; NEUT, Neutrophil; SII, systemic immune-inflammation index; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio. *p < 0.05 compared to pre and post.

Figure 4

Effect of whole Ficus carica on antioxidant enzyme activity and lipid peroxidation in the liver Different letters indicate a significant difference between groups according to the one-way ANOVA (p < 0.05) and Duncan post-hoc test. MDA, Malondialdehyde; CAT, Catalase; SOD, Superoxide Dismutase; WF, whole of Ficus carica.

Figure 5

Effect of the whole Ficus carica on memory performance assessment with Y-maze test *p < 0.05 compared to pre and post.

Figure 6

Graphical summary of the discussion illustrating the advantageous administration of Ficus carica Increase or decrease impact of oxidative stress condition Increase or decrease action of Ficus carica administration