# Fungal Pigments and Their Roles Associated with Human Health
## 5 Medical Relevance of Fungal Pigments
### Medical Roles of Melanins
antarcticus_, a heavily melanized black fungus in the class Dothideomyces of the Ascomycota phyla, were further demonstrated by its ability to survive not only the Antarctic desert but also the harsh outer space environment and cosmic radiation exposure [38; 130]. Indeed, the mechanisms for how fungal melanin molecules confer resistance to extreme heat/cold stresses and high-dosage radiations have gained wide attention from scientists [133; 134]. One of the protection mechanisms is the chelating properties of melanins towards biologically damaging free radicals generated by the physical and chemical stresses. These results are inspiring biomedical engineering in healthcare and in radiation- and thermal-protective applications [135]. Aside from melanized microscopic fungi such as yeasts and molds, melanized macroscopic mushrooms are also attracting increasing attentions. One such mushroom is the medicinal mushroom _Innotus obliquus_ (also called Chaga), a basidiomycete. This mushroom grows mainly on birch trees and is broadly distributed across the northern hemisphere in Europe, Asia, and North America. Long used in folk medicine, Chaga contains massive amounts of melanin pigments. Several research groups have reported the therapeutic potential of Chaga's bioactive pigments in countering the proliferation of cancer cells, and diabetes mellitus [136; 137]. The pigments extracted from _I. obliquus_ contain both phenolic compounds such as melanins, and triterpen such as intodiol. Interestingly, the water-soluble component of melanin complexes of _I. obliquus_ possesses insulin-sensitizing and hypoglycemic activity [138], consistent with their anti-diabetic functions. In addition, aqueous extractsof _I. obliquaus_ lowered the viability of human hepatoma (HepG2) cell lines in a dose-dependent fashion in vitro [139]. Subsequent studies revealed that the intraperitoneal administration of aqueous extracts of _I. obliquaus_ could inhibit tumor growth in vivo in mice implanted with melanoma B16-F10 cells at a dose of 20 mg/kg/d for 10 d [140]. Similarly, another study of melanin from _I. obliquaus_ showed its suppressive effect on the proliferation of HeLa 229 tumor cells [141]. Together with the above beneficial effects, the discovery of water-soluble melanin from _I. obliquaus_ in protecting DNA from carcinogenic damage [142] is also accelerating the preclinical studies of _I. obliquaus_ pigments. Results from such studies could generate significant medical and economic benefits in an environmentally friendly way (green chemistry). As shown above, melanins have many potential benefits to humans. However, their presence in pathogenic fungi can also cause detrimental effects to humans both directly as human fungal pathogens or indirectly as plant and animal fungal pathogens. For example, in the human fungal pathogens _C. neoformans_[143], _Aspergillus fumigatus_[144], _Paracoccidioides brasiliensis_[145], _Penicillium marneffei_[146], _Fonsecaepedrosoi_[147], and _Sporothrix schenckii_[148], melanin is an important virulence factor and contributes to drug resistance. Recently identified as a part of host innate immunity, platelets could be activated by exposure to _Aspergillus fumigatus_. In _A. fumigatus_, a mutant lacking melanin exhibited decreased platelet-stimulating activity, and the platelet activating effect can be mimicked by \"melanin ghosts\" [149], large isolated melanin molecules. Interestingly, melanins in _Fonsecaan monophora_, a common causal agent of chromoblastomycosis, were able to reduce Th1 cytokines and to elevate Th2 cytokines secreted by macrophages [150], likely by regulating the MAPK signalling pathway of macrophages [151], pointing out that melanins interacting with the macrophages might contribute to the immune evasion of fungal pathogen. In these species, melanin protects the invading fungal pathogen against oxidative stress within phagocytes, interferes with host cell signaling and autophagy, and masks recognition of fungal cells by the host immune system.