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Medicinal Mushrooms
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Temitope A. Oyedepo, Adetoun E. Morakinyo
More than 380 species of mushrooms have been documented to possess medicinal properties and this as a result of their high content of prebiotics (Geurts et al., 2014). Mushrooms prebiotics are known to improve the antioxidant status as a result of alterations in the composition of gut microbiota. Mushrooms play a vital role in immune response during the treatment of respiratory diseases, atherosclerosis, cancer, and other metabolic diseases (Koyyalamudi et al., 2009a, 2009b; Varshney et al., 2013). Prebiotics from mushrooms also have hypocholesterolemia properties that help reduce lipogenic gene expression (Hmgcr, Fasn, Srebp1c, and Acaca) and genes responsible for reverse cholesterol transport (Abcg5 and Abcg8) significantly, as well as an increase in Low Density Lipoprotein Receptor gene expression in the liver (Meneses et al., 2016). Ganoderma lucidium is a mushroom that has been documented to reduce obesity in mice by altering the composition of gut microbiota (Xu and Zhang, 2015).
Treatment of Vulnerable Plaques: Current and Future Strategies
Published in Levon Michael Khachigian, High-Risk Atherosclerotic Plaques, 2004
Leonard Kritharides, David Brieger, S. Benedict Freedman, Harry C. Lowe
Clearance of cholesterol from LDL and HDL by the liver is relevant to this process and involves the selective uptake of cholesteryl ester by SRB-1180 and the excretion of biliary sterols by the expression of ABCG5 and ABCG8.181 SRB-1 is also likely to play a role in facilitating cholesterol mobilization from peripheral stores.182 Although over-expression of SRB-1 lowers plasma HDLc, its role in mediating net clearance of cholesterol from tissues is supported by accelerated atherosclerosis with cardiac ischemia in mice deficient in SRB-1.183 Because several key components of the reverse cholesterol transport pathway are regulated by ligands for LXR and RXR, these may be suitable targets for future therapies, and there is some indication they can be modulated by PPAR ligands.
Inhibiting Insulin Resistance and Accumulation of Triglycerides and Cholesterol in the Liver
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
The liver is the primary site of elimination of cholesterol in the body and this is done by direct secretion into bile through ATP-binding cassette G5 and G8 transporters or conversion into bile acids.330 The rate-limiting enzyme for bile acids synthesis is cholesterol 7α-hydroxylase (CYP7A1), which catalyzes the conversion of cholesterol to 7α cholesterol.331 The transcription of ABCG5 and ABCG8 transporters and CYP7A1 is induced, at least, by liver X receptors activation.332 The root bark of Acanthopanax koreanum Nakai contains (−)-acanthoic acid (Figure 3.25) also known as (−)-pimara-9(11),15-dien-19-oic acid, which is an agonist for liver X receptor in vitro with IC50 below 10 µM.333 Evidence indicates that liver X receptors not only induce genes involved in cholesterol efflux, but also repress inflammatory genes after tumor necrosis factor-α or interleukin-1β stimulation,56 probably explaining why this diterpene given orally and prophylactically to Wistar rats at a dose of 100 mg/kg/day for 4 days attenuated carbon tetrachloride induced liver insults as evidenced by decreased plasma levels of aspartate aminotransferase.334 Acanthoic acid given to C57BL/6 mice orally three times per weeks at a dose of 50 mg/kg for 8 weeks lowered plasma aspartate aminotransferase, tumor necrosis factor-α induced by carbon tetrachloride poisoning.335 This diterpene improved hepatic cytoarchitecture as evidenced by decreased hepatocyte damage.335 At the hepatic level, acanthoic acid upregulated liver X receptor and reduced the nuclear translocation of nuclear factor-κB.335
What can we learn from the platelet lipidome?
Published in Platelets, 2023
Gaëtan Chicanne, Jean Darcourt, Justine Bertrand-Michel, Cédric Garcia, Agnès Ribes, Bernard Payrastre
However, whether specific platelet lipidomic profiles may become diseases signature remains to be established. Moreover, how altered platelet lipidome can be involved in platelet-dependent pathologies is still poorly understood. Yet, some inherited pathologies are directly linked to platelet lipid modifications. This includes the loss of PS exposure due to TMEM16F scramblase mutations impairing the procoagulant function of platelets in the bleeding Scott syndrome [32], the rare inherited cPLA2 deficiency leading to platelet dysfunction [21], the decreased expression of PLCβ2 linked to hypo-responsive platelets [33], or the loss of function of the PI(4,5)P2 5-phosphatase affecting platelet responses in the LOWE syndrome [34]. Some mouse models have also pointed to new important lipid-related pathways that should stimulate to prioritize a lipidomic analysis in patients. For instance, as mentioned above, mice lacking sphingomyelin phosphodiesterase 1 have platelet dysfunction suggesting that human platelets deficient in this enzyme, such as platelets from Niemann-Pick patients, may be affected. A mouse model of sitosterolemia caused by a mutation in the ABCG5 or ABCG8 transporter genes has linked the accumulation of free plant sterols in platelet membranes to dysregulation of platelet functions leading to macrothrombocytopenia and bleeding [35]. Lipidomic studies on platelets from sitosterolemia patients should bring interesting information as well as potential diagnostic and disease monitoring markers.
Beyond the Usual Suspects: Expanding on Mutations and Detection for Familial Hypercholesterolemia
Published in Expert Review of Molecular Diagnostics, 2021
Shirin Ibrahim, Joep C. Defesche, John J.P. Kastelein
Variants in the genes encoding adenosine triphosphate-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) have also been shown to affect LDL-C levels. ABCG5 and ABCG8 form a heterodimer that is responsible for the transmembrane transport of sterols, in particular, plant sterols [41]. In the intestine, the complex is involved in the transport of sterols from the enterocyte into the intestinal lumen, whereas in the liver it promotes the transport of sterols into the bile. Mutations in ABCG5 and ABCG8 can cause sitosterolemia, an autosomal recessive disorder whereby plant sterols accumulate in blood and tissues. Studies have shown an association between hypercholesterolemia and sitosterolemia in the general population [41]. With the expansion of NGS panels in FH patients, variants in ABCG5 and ABCG8 have been frequently discovered. Patients with sitosterolemia can present with xanthomas and premature CAD, characteristics that closely mimic the clinical FH phenotype [56]. Studies by Tada et al. and Nomura et al. suggest that heterozygous pathogenic variants in the ABCG5/ABCG8 can worsen the clinical expression of FH in terms of additional elevation of LDL-C levels and cardiovascular risk [57,58]. Recently, we have also addressed this issue and could not confirm these findings [41].
ABCG5 and ABCG8 gene variations associated with sitosterolemia and platelet dysfunction
Published in Platelets, 2021
Jose María Bastida, Rocío Benito, José Ramón González-Porras, José Rivera
Among the variants that have been reported to cause sitosterolemia, only 24 have been associated with macrothrombocytopenia, being the most prevalent ones R419 H and R446* in ABCG5, and R263Q and W361X in ABCG8 [1,8,12]. All these variants are rare (allele frequency lower than 1 × 10−3) and all, except R263Q in ABCG8, are classified as pathogenic or likely pathogenic according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology recommendations and ClinVar criteria (variant information available at https://varsome.com/) [30,31]. Surprisingly, certain variants such as R419 H and R446X in ABCG5 are associated with thrombocytopenia in some but not all patients. This suggests a potential key role of the type of sitosterol exposure, and/or the contribution of additional unknown mechanisms in platelet biogenesis disruption in sitosterolemia [8,12].