Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study.

Well-characterized and standardized extracts of a Mexican genotype of Ganoderma lucidum (Gl), a medicinal mushroom, cultivated on oak sawdust (Gl-1) or oak sawdust plus acetylsalicylic acid (Gl-2, ASA), have been shown to exert antioxidant, hypocholesterolemic, anti-inflammatory, prebiotic, and anticancer properties. However, toxicity analyses still need to be carried out. Different doses of these Gl-1 or Gl-2 extracts were administered to Wistar rats for 14 days in a repeated dose oral toxicity study. We assessed the external clinical signs, biochemical parameters, liver and kidney tissues, injury and inflammation biomarkers, gene expression, inflammatory responses, proinflammatory mediators, and gut microbiota. Gl extracts had no significant adverse, toxic or harmful effects on male and female rats compared to the control groups. No injury or dysfunction were recorded in the kidney or liver, as there were no significant abnormal variations in organ weight, tissue histopathology, serum biochemical parameters (C-reactive protein, creatinine, urea, glucose, ALT and AST transaminases, TC, LDL-c, TG, HDL-c), urinary parameters (creatinine, urea nitrogen, albumin, the albumin-to-creatinine ratio, glucose), injury and inflammatory biomarkers (KIM-1/TIM-1, TLR4, and NF-кB protein expression; IL-1ß, TNF-α and IL-6 gene expression), or the expression of genes linked to cholesterol metabolism (HMG-CoA, Srebp2, Ldlr). Gl-1 and Gl-2 extracts showed prebiotic effects on the gut microbiota of male and female Wistar rats. Bacterial diversity and relative bacterial abundance (BRA) increased, positively modulating the Firmicutes/Bacteroidetes ratio. The ASA (10 mM) added to the substrate used for mushroom cultivation changed properties and effects of the Gl-2 extract on Wistar rats. The no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg body weight/day of Gl-1 or Gl-2 extracts. Clinical trials are recommended for further exploring the potential therapeutic applications of studied extracts.

Nutritional Composition and Bioactive Compounds of Quelites Consumed by Indigenous Communities in the Municipality of Juquila Vijanos, Sierra Norte of Oaxaca, Mexico.

The indigenous communities of Mexico have a long tradition of consuming quelites. In this research, eight species of quelites that are traditionally consumed by indigenous communities of the Sierra Norte of Oaxaca, Mexico, were characterized: Eryngium foetidum L., Galinsoga parviflora Cav., Calceolaria mexicana Benth., Andinocleome magnifica (Briq.) Iltis & Cochrane, Cleoserrata speciosa (Raf.) H.H. Iltis, Phytolacca icosandra L., Cestrum nocturnum L. and Solanum nigrescens M.Martens & Galeotti. The ethnobotanical information of these species was recorded and the proximate composition, mineral content, and total phenolic and flavonoid content were determined. The antioxidant capacity of the samples was also investigated using ABTS (2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), DPPH (2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl), and ORAC (oxygen radical absorption capacity) methods. Quelites are available in the dry and rainy season. Quelites were found to have low energy contents while being good sources of fiber, of which A. magnifica possessed the highest concentration (8.61 ± 0.35 g/100 g fresh weight FW). Quelites were also found to provide essential minerals, with the primary contributions being potassium (4097.35 ± 12.28 mg/100 g FW) in C. mexicana, calcium (2418.63 ± 22.91 mg/100 g FW) in S. nigrescens, magnesium (1021.83 ± 10.58 mg/100 g FW) in E. foetidum, among others. C. speciosa and C. mexicana exhibited the highest concentration of phenols and flavonoids, which were found to be associated with higher antioxidant capacity. The quelites analyzed in this study are a potential source of accessible, nutritious, and healthy food, and can potentially help improve food security and health.

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

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 ß-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.

Dietary fat differentially influences the lipids storage on the adipose tissue in metabolic syndrome patients.

PURPOSE: Adipose tissue is now recognized as a highly active metabolic and endocrine organ. Our aim was to investigate the effect of the dietary fat on the two main adipose tissue functions, endocrine and lipid store, by analyzing the adipose tissue gene expression from metabolic syndrome patients. METHODS: A randomized, controlled trial conducted within the LIPGENE study assigned 39 metabolic syndrome patients to 1 of 4 isoenergetic diets: (1) high-saturated fatty acid (HSFA), (2) high-monounsaturated fatty acid (HMUFA), (3) low-fat, high-complex carbohydrate diet supplemented with long-chain n-3 fatty acids (LFHCC n-3), and (4) low-fat, high-complex carbohydrate diet supplemented with placebo (LFHCC), for 12 weeks each. A fat challenge reflecting the fatty acid composition as the original diets was conducted post-intervention. RESULTS: The long-term consumption of HSFA, LFHCC, and LFHCC n-3 diets, but not HMUFA diet, decreased the perilipin fasting mRNA levels. LFHCC diet consumption increased fasting FABP4 expression, while it was reduced by the consumption of LFHCC n-3 diet. LFHCC meal reduced, while LFHCC n-3 meal intake increased postprandial CAV1 expression. CONCLUSION: The quantity and quality of dietary fat induce differential lipid storage and processing related gene expression, which may interact with the expression of adipokines through common regulatory mechanisms.

Postprandial inflammatory response in adipose tissue of patients with metabolic syndrome after the intake of different dietary models.

SCOPE: Dysfunctional adipose tissue may be an important trigger of molecular inflammatory pathways that cause cardiovascular diseases. Our aim was to determine whether the specific quality and quantity of dietary fat produce differential postprandial inflammatory responses in adipose tissue from metabolic syndrome (MetS) patients. METHODS AND RESULTS: A randomized, controlled trial conducted within the LIPGENE study assigned MetS patients to 1 of 4 diets: (i) high-saturated fatty acid (HSFA), (ii) high-monounsaturated fatty acid (HMUFA), (iii) low-fat, high-complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids (PUFA) (LFHCC n-3), and (iv) low-fat, high-complex carbohydrate diet supplemented with placebo (LFHCC), for 12 wk each. A fat challenge reflecting the fatty acid composition as the original diets was conducted post-intervention. We found that p65 gene expression is induced in adipose tissue (p=0.003) at the postprandial state. In addition, IκBα (p<0.001), MCP-1 (p<0.001) and IL-1ß (p<0.001) gene expression was equally induced in the postprandial state, regardless of the quality and quantity of the dietary fat. Notably, IL-6 transcripts were only detected in the postprandial state. CONCLUSIONS: Our results indicate that individuals with MetS typically exhibit exacerbated adipose tissue postprandial inflammatory responses, which seem to be independent of the quality and quantity of dietary fat.