# Fungal Pigments and Their Roles Associated with Human Health
## 2 Types of Fungal Pigments and Their Relevance to Human Health
### Azaphilones  
Azaphilones are a structurally variable group of fungal secondary metabolites (polyketide derivatives) [63], namely pigments with a highly oxygenated pyrone-quinone bicyclic core usually known as isochromene and a chiral quaternary centre [64, 65]. Both a pyrone-quinone backbone and a chiral quaternary centre (Figure 2) are essential for compounds to be classified as azaphilones [66]. Azaphilone is so designated because of its ready insertion of nitrogen. For example, ammonia readily converts the pyran oxygen of monascorubrin into the violet-colored nitrogen analog monascorubramine (Figure 3) [67]. The azaphilone pigments are produced by a plethora of the ascomycetous and basidiomycetous fungi, particularly the former [68], including the genera _Aspergillus_, _Penicillium_, _Chaetomium_, _Talaromyces_, _Pestalotiopsis_, _Phomopsis_, _Emericella_, and _Epicoccum_, as well as _Monascus_ and _Hypoxylon_, where they give rise to the yellow, red, or green hues of fruiting bodies and/or mycelia [69]. Fungal azaphilones, structurally bearing the isochromane-like ring, possess a broad-spectrum of biological activities including monoamine oxidase inhibition, phospholipase A2 inhibition, tumor promotion suppression, gpl20-CD4 binding inhibition, and acyl-CoA: cholesteroltransferase (AGAT) inhibition. However, the relationships between the structures of azaphilones, their spectrum of activities, and the corresponding mechanistic modes of action remain elusive [66]. Monascin and anakfalavin (Figure 4B) are two yellow pigments of the azaphilonoid group. The fungal genus _Monascus_-derived monascin and anakfalavin have been found to petently inhibit preadipocyte differentiation, and promote lipolysis of mature adipocytes [70]. Furthermore, these two pigments are able to reduce blood lipids as well as lower the synthesis and accumulation of triglycerides (TG) [71]. For example, [PERSON] et al. (2013) investigated the effects of eight-week administrations of monascin and anakfalavin on obesity factors using obese rats fed with a high-fat diet [72]. Their work illustrated the involvement of these two _Monascus_ azaphilones in the modulation of preadipocyte differentiation, lipogenesis, and lipid absorption, highlighting their potential in the development of hypolipidemic drugs. Monacolin K (viz. lovastatin) is a statin compound and previously thought to be a hypolipidemic component of _Monascus_-fermented products. While earlier studies suggested anti-obesity effects of monacolin K (Figure 4A), recent investigations indicated that monascin and anakfalavin (Figure 4B), rather than monacolin K, were likely the major players in the _Monascus_-mediated amelioration of diabetes and fatty liver [73]. Figure 3: Azaphilone pigments derived from the yeast _Monascus_. Figure 2: Azaphilonoid scaffold. Indeed, there is mounting evidence that a long-term high-dosage administration of monacolin K might lead to numerous side effects such as rhabdomyolysis and reduction in the level of coenzyme Q\({}_{10}\) (CoQ\({}_{10}\)). Furthermore, although monacolin K reduces the serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels, it also substantially reduces high-density lipoprotein cholesterol (HDL-C) levels. On the other hand, [PERSON] et al. (2010) showed that monascin and anakfalavin could increase HDL-C levels significantly while imposing no damage on the liver or kidneys [68]. In addition, monascin has been shown to protect the liver from chemical damage via its anti-inflammatory effect [74]. Other work with monascin has indicated that it significantly inhibits peroxynitrite (ONOO-; PN), and ultraviolet light B (UVB)-induced skin carcinogenesis [75]. Together, the above results suggest that monascin and anakfalavin possess hypolipidemic, anti-atherosclerosis, antioxidative, and anti-inflammatory activities, thereby rendering them promising compounds that may be of value in the prevention and treatment of cardiovascular diseases [73].