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.
Highlights
The prevalence of overweight and obesity has increased considerably in countries with a food pattern transition based on the consumption of processed foods
We have shown that the consumption of standardized G. lucidum (Gl)-1 and Gl-2 extracts of Ganoderma lucidum, derived from basidiomata of Mexican genetic resources cultivated under controlled conditions, represents a promising alternative for the treatment of hypercholesterolemia
Our evidences indicate that either the amount of glucans or the presence of several previously reported bioactive compounds can regulate different mechanisms associated with cholesterol metabolism
Summary
The prevalence of overweight and obesity has increased considerably in countries with a food pattern transition based on the consumption of processed foods. Cholesterol homeostasis in the body is mainly controlled by the endogenous synthesis, intestinal absorption, and hepatic excretion of dietary cholesterol These processes are mediated by several transcription factors, which are fundamental to understanding the regulation of cholesterol metabolism. Hepatic cholesterol in the form of oxysterols represents a group of ligands for the liver X receptor (LXR) transcription factor, which upregulates the expression of the sterol regulatory element binding transcription factor 1c (Srebp1c) [5]. This factor activates the expression of lipogenic genes [6]. Isoforms of LXR, LXR-α and LXR-β, are capable of increasing the expression of several genes involved in bile acid synthesis, such as cholesterol 7 alpha-hydroxylase (Cyp7a1), as well as those associated with reverse cholesterol transport, including the ATP-binding cassette subfamily G members 5 and 8 (Abcg and Abcg8) and the ATP-binding cassette subfamily A (Abca1), among others
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