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. 2016 Jul 20;11(7):e0159631.
doi: 10.1371/journal.pone.0159631. eCollection 2016.

Hypocholesterolemic Properties and Prebiotic Effects of Mexican Ganoderma lucidum in C57BL/6 Mice

María E Meneses  1 , Daniel Martínez-Carrera  2 , Nimbe Torres  3 , Mónica Sánchez-Tapia  3 , Miriam Aguilar-López  3 , Porfirio Morales  2 , Mercedes Sobal  2 , Teodoro Bernabé  2 , Helios Escudero  2 , Omar Granados-Portillo  3 , Armando R Tovar  3
Affiliations

Hypocholesterolemic Properties and Prebiotic Effects of Mexican Ganoderma lucidum in C57BL/6 Mice

María E Meneses et al. PLoS One. .

Abstract

Edible and medicinal mushrooms contain bioactive compounds with promising effects on several cardiovascular risk biomarkers. However, strains of Ganoderma lucidum of Mexican origin have not yet been studied. Standardized extracts of G. lucidum (Gl) were given to C57BL/6 mice fed a high-cholesterol diet compared with the drug simvastatin. The effects of the extracts on serum biochemical parameters, liver lipid content, cholesterol metabolism, and the composition of gut microbiota were assessed. Acetylsalicylic acid (10 mM) added to the cultivation substrate modulated properties of Gl extracts obtained from mature basidiomata. Compared to the high-cholesterol diet group, the consumption of Gl extracts significantly reduced total serum cholesterol (by 19.2% to 27.1%), LDL-C (by 4.5% to 35.1%), triglyceride concentration (by 16.3% to 46.6%), hepatic cholesterol (by 28.7% to 52%) and hepatic triglycerides (by 43.8% to 56.6%). These effects were associated with a significant reduction in the expression of lipogenic genes (Hmgcr, Srebp1c, Fasn, and Acaca) and genes involved in reverse cholesterol transport (Abcg5 and Abcg8), as well as an increase in Ldlr gene expression in the liver. No significant changes were observed in the gene expression of Srebp2, Abca1 or Cyp7a1. In several cases, Gl-1 or Gl-2 extracts showed better effects on lipid metabolism than the drug simvastatin. A proposed mechanism of action for the reduction in cholesterol levels is mediated by α-glucans and β-glucans from Gl, which promoted decreased absorption of cholesterol in the gut, as well as greater excretion of fecal bile acids and cholesterol. The prebiotic effects of Gl-1 and Gl-2 extracts modulated the composition of gut microbiota and produced an increase in the Lactobacillaceae family and Lactobacillus genus level compared to the control group, high-cholesterol diet group and group supplemented with simvastatin. Mexican genetic resources of Gl represent a new source of bioactive compounds showing hypocholesterolemic properties and prebiotic effects.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Effect of experimental diets on lipid accumulation in the liver of C57BL/6 mice.
A: Hepatic tissue stained with haematoxylin and eosin, showing differences in lipid accumulation among experimental groups. B: Lipid accumulation in the liver assessing levels of cholesterol and triglycerides. Data are presented as mean ± SEM. Means in a column showing differing letters indicate statistically significant difference, p < 0.05. Values correspond to one way ANOVA from the Bonferroni's Multiple Comparison Test. Ctrl: Control diet. Ch: High cholesterol diet (0.5%). Ch+Sim: High cholesterol diet (0.5%) + simvastatin (0.03 g/100 g). Ch+Gl-LD-1: High cholesterol diet (0.5%) + Gl-1 extract, low dose (0.5%). Ch+Gl-HD-1: High cholesterol diet (0.5%) + Gl-1 extract, high dose (1.0%). Ch+Gl-LD-2: High cholesterol diet (0.5%) + Gl-2 extract, low dose (0.5%). Ch+Gl-HD-2: High cholesterol diet (0.5%) + Gl-2 extract, high dose (1.0%).
Fig 2
Fig 2. Effect of experimental diets on the expression of genes related to lipogenic processes in the liver of C57BL/6 mice.
A: Lipogenic genes. B: Genes associated to cholesterol metabolism. Data are presented as mean ± SEM. Means in a column showing differing letters indicate statistically significant difference, p < 0.05. Values correspond to one way ANOVA from the Bonferroni's Multiple Comparison Test. Ctrl: Control diet. Ch: High cholesterol diet (0.5%). Ch+Sim: High cholesterol diet (0.5%) + simvastatin (0.03 g/100 g). Ch+Gl-LD-1: High cholesterol diet (0.5%) + Gl-1 extract, low dose (0.5%). Ch+Gl-HD-1: High cholesterol diet (0.5%) + Gl-1 extract, high dose (1.0%). Ch+Gl-LD-2: High cholesterol diet (0.5%) + Gl-2 extract, low dose (0.5%). Ch+Gl-HD-2: High cholesterol diet (0.5%) + Gl-2 extract, high dose (1.0%).
Fig 3
Fig 3. Abundance of proteins involved in the lipogenesis process in the liver (Srebp1c, Acaca and Fasn/Actin).
Ctrl: Control diet. Ch: High cholesterol diet (0.5%). Ch+Sim: High cholesterol diet (0.5%) + simvastatin (0.03 g/100 g). Ch+Gl-LD-1: High cholesterol diet (0.5%) + Gl-1 extract, low dose (0.5%). Ch+Gl-HD-1: High cholesterol diet (0.5%) + Gl-1 extract, high dose (1.0%). Ch+Gl-LD-2: High cholesterol diet (0.5%) + Gl-2 extract, low dose (0.5%). Ch+Gl-HD-2: High cholesterol diet (0.5%) + Gl-2 extract, high dose (1.0%).
Fig 4
Fig 4. Effect of the experimental diets on C57BL/6 mice.
A: Expression of genes related to reverse cholesterol transport in the liver. B: Amount of bile acids and cholesterol in feces. Data are presented as mean ± SEM. Means in a column showing differing letters indicate statistically significant difference, p < 0.05. Values correspond to one way ANOVA from the Bonferroni's Multiple Comparison Test. Ctrl: Control diet. Ch: High cholesterol diet (0.5%). Ch+Sim: High cholesterol diet (0.5%) + simvastatin (0.03 g/100 g). Ch+Gl-LD-1: High cholesterol diet (0.5%) + Gl-1 extract, low dose (0.5%). Ch+Gl-HD-1: High cholesterol diet (0.5%) + Gl-1 extract, high dose (1.0%). Ch+Gl-LD-2: High cholesterol diet (0.5%) + Gl-2 extract, low dose (0.5%). Ch+Gl-HD-2: High cholesterol diet (0.5%) + Gl-2 extract, high dose (1.0%).
Fig 5
Fig 5. Effect of experimental diets on the gut microbiota from five different groups of C57BL/6 mice.
Relative abundance at the bacterial family level. Ctrl: Control diet. Ch: High cholesterol diet (0.5%). Ch+Sim: High cholesterol diet (0.5%) + simvastatin (0.03 g/100 g). Ch+Gl-HD-1: High cholesterol diet (0.5%) + Gl-1 extract, high dose (1.0%). Ch+Gl-HD-2: High cholesterol diet (0.5%) + Gl-2 extract, high dose (1.0%).
Fig 6
Fig 6. Effect of experimental diets on the gut microbiota from five different groups of C57BL/6 mice.
A: Relative abundance at the bacterial phyla level. B: DNA abundance of Lactobacillus by RT-PCR. Ctrl: Control diet. Data are presented as mean ± SEM. Means in a column showing differing letters indicate statistically significant difference, p < 0.05. Values correspond to one way ANOVA from the Bonferroni's Multiple Comparison Test. Ch: High cholesterol diet (0.5%). Ch+Sim: High cholesterol diet (0.5%) + simvastatin (0.03 g/100 g). Ch+Gl-HD-1: High cholesterol diet (0.5%) + Gl-1 extract, high dose (1.0%). Ch+Gl-HD-2: High cholesterol diet (0.5%) + Gl-2 extract, high dose (1.0%).
Fig 7
Fig 7. A heatmap showing the relative abundance of bacterial genera, which cover 95% of all reads assigned to this level in mice groups studied.
Ctrl: Control diet. Ch: High cholesterol diet (0.5%). Ch+Sim: High cholesterol diet (0.5%) + simvastatin (0.03 g/100 g). Ch+Gl-HD-1: High cholesterol diet (0.5%) + Gl-1 extract, high dose (1.0%). Ch+Gl-HD-2: High cholesterol diet (0.5%) + Gl-2 extract, high dose (1.0%).
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Grants and funding

The research work was supported by the National Council of Science and Technology (CONACYT; www.conacyt.mx) in Mexico, through the Research Project “105 Genómica de las Propiedades Funcionales y Medicinales de los Hongos Comestibles de México,” directed by DMC; CONACYT also supported the Postdoctoral Position for MEM (agreement no. 290754). A grant from Dannon Institute of Mexico was received by NT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.