Chiliadenus iphionoides Reduces Body Weight and Improves Parameters Related to Hepatic Lipid and Glucose Metabolism in a High-Fat-Diet-Induced Mice Model of NAFLD

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become an epidemic with increasing prevalence. Limited treatment options and poor adherence emphasize the urgent need for novel therapies for the treatment and/or prevention of NAFLD. Bioactive natural compounds found in medicinal plants are promising as novel therapeutic agents for NAFLD. Chiliadenus iphionoides, a medicinal plant with several health-promoting properties, is an encouraging candidate. The current study aimed to elucidate the metabolic effects of C. iphionoides consumption in a high-fat-diet (HFD)-induced model of NAFLD. Male C57BL/6J mice (n = 40, 7-8-week-old) were fed a HFD (60% fat) with/without 0.5 or 2.5 gr C. iphionoides for fifteen weeks. Diet supplementation with C. iphionoides significantly ameliorated HFD-induced weight gain. Likewise, liver and adipose tissue weights were profoundly lower in the C. iphionoides-fed groups. Reduced liver steatosis in those groups was corroborated by histology, plasma liver enzyme levels, and lipid profile, indicating improved liver function and lipid metabolism in addition to enhanced insulin sensitivity. The addition of C. iphionoides to an obesogeneic diet can beneficially alleviate metabolic alterations and may be a practicable strategy for the management of NAFLD.

Keywords: Chiliadenus iphionoides; NAFLD; glucose tolerance; lipid metabolism.

Figure 1

Effects of Chiliadenus iphionoides supplementation on serum lipid profile. Male C57BL/6J mice were fed with normal diet (ND), high-fat diet (HFD), high-fat diet + 0.5 mg/kg Chiliadenus iphionoides (HFD + 0.5CI), high-fat diet + 2.5 mg/kg Chiliadenus iphionoides (HFD + 2.5CI) for fifteen weeks. Values are expressed as mean ± SEM (n = 5). Different letters denote significant difference (p < 0.05, Tukey’s HSD).

Figure 2

Effects of Chiliadenus iphionoides supplementation on serum liver enzymes. Male C57BL/6J mice were fed with normal diet (ND), high-fat diet (HFD), high-fat diet + 0.5 mg/kg Chiliadenus iphionoides (HFD + 0.5CI), high-fat diet + 2.5 mg/kg Chiliadenus iphionoides (HFD + 2.5CI) for fifteen weeks. Values are expressed as mean ± SEM (n = 6). Different letters denote significant difference (p < 0.05, Tukey’s HSD). AST—aspartate aminotransferase, ALT—alanine aminotransferase.

Figure 3

Effects of Chiliadenus iphionoides supplementation on glucose homeostasis. Male C57BL/6J mice were fed with normal diet (ND), high-fat diet (HFD), high-fat diet + 0.5 mg/kg Chiliadenus iphionoides (HFD + 0.5CI), high-fat diet + 2.5 mg/kg Chiliadenus iphionoides (HFD + 2.5CI) for fifteen weeks. (A) An oral glucose tolerance test for 120 min was performed at week 14; (B) Glucose tolerance test measured as the area under the curve (AUC); (C) Mean fasting blood glucose concentration at sacrifice; (D) Insulin serum levels at sacrifice; (E) Homeostatic model assessment of insulin resistance index (HOMA-IR). Values are expressed as mean ± SEM (ND = 9, HFD groups n = 10). Different letters denote significant difference (p < 0.05, Tukey’s HSD).

Figure 4

Effects of Chiliadenus iphionoides supplementation on histology section of the perilobular region of the liver. Male C57BL/6J mice were fed with normal diet (ND), high-fat diet (HFD), high-fat diet + 0.5 mg/kg Chiliadenus iphionoides (HFD + 0.5CI), high-fat diet + 2.5 mg/kg Chiliadenus iphionoides (HFD + 2.5CI) for fifteen weeks. (A) Histological evaluation of the liver using H&E stain versus artificial intelligence; (B) Hepatocytic vacuolation evaluated by semi-quantitive grade presented as H&E stain or by % of fatty vacuoles in hepatocytes presented by artificial intelligence. Values are expressed as mean ± SEM (n = 4). Different letters denote significant difference (p < 0.05, Tukey’s HSD) asterisk denotes significant difference (p < 0.05, Student’s t-test).

Figure 5

Effect of Chiliadenus iphionoides supplementation on genes related to liver carbohydrate and lipid metabolism. Male C57BL/6J mice were fed with normal diet (ND), high-fat diet (HFD), high-fat diet + 0.5 mg/kg Chiliadenus iphionoides (HFD + 0.5CI), high-fat diet + 2.5 mg/kg Chiliadenus iphionoides (HFD + 2.5CI) for fifteen weeks. (A) Gene expression of CD36, Fasn, SREBP-1c, PPAR-α, and CPT1 levels; (B) Gene expression of iNOS and SAA1 levels were measured. Values are expressed as mean ±SEM (ND, HFD, HFD + 0.5CI n = 10, HFD + 2.5CI n = 9). Different letters denote significant difference (p < 0.05, Tukey’s HSD) asterisk denotes significant difference (p < 0.05, Student’s t-test).

Figure 6

Effect of Chiliadenus iphionoides supplementation on proteins related to liver carbohydrate and lipid metabolism. Male C57BL/6J mice were fed with normal diet (ND), high-fat diet (HFD), high-fat diet + 0.5 mg/kg Chiliadenus iphionoides (HFD + 0.5CI), high-fat diet + 2.5 mg/kg Chiliadenus iphionoides (HFD + 2.5CI) for fifteen weeks. (A) Protein expression of pAMPK/AMPK ratio; (B) Protein expression of pAKT/AKT ratio; (C) Protein expression of pACC/ACC ratio. Values are expressed as mean ±SEM.