Cardiovascular diseases include diseases of the heart, vascular diseases of the brain, and diseases of blood vessels (Mendis et al. 2011). Elevated levels of plasma cholesterol are responsible for these diseases, as they play a major role in atherosclerosis, the clogging or hardening of arteries caused by accumulations of fatty deposits (usually cholesterol) (Miller 2001). These diseases were responsible for 17.3 million deaths per year in 2015, and are the leading source of deaths worldwide (GBD 2015). Inhibition of de novo synthesis of cholesterol was demonstrated to be an effective method for reducing plasma cholesterol levels (Miller 2001). The rate determining step is the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate by HMG-CoA reductase; hence selective inhibition of the latter enzyme, can reduce the synthesis of cholesterol (Brown et al. 1976; Endo et al. 1976). The most important class of HMG-CoA reductase inhibitors are the statins, which are derived from fungal natural products and contain two types of structures moieties, a hexahydro-naphthalene system and a β-hydroxylactone system. The statins are also the best-selling class of pharmaceutical drugs, with an annual turnover in the range of US$50 billion. Therefore, the most important compounds of this type are treated here.
Brown et al. (1978) isolated compactin (22) (also known as mevastatin and ML-236B) from Penicillium brevicompactum as an antibiotic, but its hypocholesterolemic activity was later revealed by Endo et al. (1976), who used the name “ML-236B”. Later another HMG-CoA reductase inhibitor named mevinolin (23) was isolated from Aspergillus terreus by Alberts et al. (1980). The first statin drug approved by the United States Food and Drug Administration was lovastatin (24) in 1987 (Jahromi et al. 2012). Although lovastatin is produced by several species of Penicillium (Endo et al. 1976), Monascus species (Miyake et al. 2006; Sayyad et al. 2007), Doratomyces, Gymnoascus, Hypomyces, Phoma and Trichoderma, the commercialized product is derived from Aspergillus terreus (Jahromi et al. 2012). Another statin containing a product called Xuezhikang or “red yeast rice extract”, produced by the fermentation of Monascus spp., has been widely used in China for centuries for treating circulatory disorders. The low density lipoprotein lowering ability of “red yeast rice extract” is clinically proven and contains lovastatin (Lu et al. 2008).
Solid state fermentation, or submerged cultures, can be used for the production of lovastatin (Ruddiman and Thomson 2001; Lai et al. 2003; Suryanarayan 2003; Wei et al. 2007; Jaivel and Marimuthu 2010; Pansuriya and Singhal 2010; Jahromi et al. 2012), but production is significantly higher in the former (Jaivel and Marimuthu 2010; Jahromi et al. 2012). Sorghum grain, wheat bran, rice and corn are used as substrates for solid state fermentation (Wei et al. 2007; Jaivel and Marimuthu 2010; Jahromi et al. 2012). Basidiomycetes are a good source of nutrient supplements for humans. Certain molecules in mushrooms can modify cholesterol absorption, metabolism, and also modulate the gene expression related to cholesterol homeostasis (Gil-Ramı´rez et al. 2016). Grifola frondosa, Hypsizigus marmoreus and Pleurotus ostreatus were able to differentially modulate the gene expression patterns of mice livers (Gil-Ramı´rez et al. 2016). Of the biologically active compounds from fungi that can reduce the amounts of cholesterol in the blood, the most studied are ergosterol derivatives (Gil-Ramı´rez et al. 2016). The cholesterol-lowering properties are mainly caused by the structural similarity with cholesterol (Gil-Ramı´rez et al. 2016). Further, the biological activity of β-glucans and chitin may be due to their binding abilities to cholesterol receptors (Gil-Ramı´rez et al. 2016).
Francia et al. (1999) recorded 16 species of edible mushrooms with biological activities against cardiovascular disease. Species of the genera Auricularia (Fan et al. 1989), Ganoderma (Kabir et al. 1988), Grifola (Kubo and Namba 1997), Pleurotus (Bobeck et al. 1991) and Tremella (Cheung 1996) have been reported to contain cholesterol lowering compounds. Ophiocordyceps sinensis has also been shown to reduce total cholesterol levels, which has been attributed to the fact that it contains polysaccharide “CS-F30” composed of galactose, glucose and mannose (Kiho et al. 1996). For instance, low density lipoprotein cholesterol levels were reported to be reduced by Auricularia auricula–judae (Fan et al. 1989) and Tremella fuciformis (Cheung 1996), and triglyceride levels were reported to be reduced by Grifola frondosa (Kubo and Namba 1997), Lentinula edodes (Kabir and Kimura 1989) and Ophiocordyceps sinensis (Kiho et al. 1996).