Different skin colour among individuals is determined by the varying amount and types of melanin pigment. Melanin is produced in melanocytes, a type of dendritic cell located in the basal layer of the epidermis, through the process of melanogenesis. Melanogenesis consists of a series of biochemical and enzymatic reactions catalysed by tyrosinase and other tyrosinase-related proteins, leading to the formation of two types of melanin, eumelanin and pheomelanin. Melanogenesis can be regulated intrinsically by several signalling pathways, including the cAMP/PKA, SCF/c-kit and Wnt/β-catenin signalling pathways. Ultraviolet radiation (UVR) is the major extrinsic factor in the regulation of melanogenesis, through the generation of reactive oxygen species (ROS). Antioxidants or antioxidant systems, with the ability to scavenge ROS, may decrease melanogenesis. This review focuses on the two main cellular antioxidant systems, the thioredoxin (Trx) and glutathione (GSH) systems, and discusses their roles in melanogenesis. In the Trx system, high levels/activities of thioredoxin reductase (TrxR) are correlated with melanin formation. The GSH system is linked with regulating pheomelanin formation. Exogenous addition of GSH has been shown to act as a depigmenting agent, suggesting that other antioxidants may also have the potential to act as depigmenting agents for the treatment of human hyperpigmentation disorders.

Lymphoma is a blood cancer comprising various subtypes. Although effective therapies are available, some patients fail to respond to treatment and can suffer from side effects. Antioxidant systems, especially the thioredoxin (Trx) and glutathione (GSH) systems, are known to enhance cancer cell survival, with thioredoxin reductase (TrxR) recently reported as a potential anticancer target. Since the GSH system can compensate for some Trx system functions, we investigated its response in three lymphoma cell lines after inhibiting TrxR activity with [Au(d2pype)2]Cl, a known TrxR inhibitor. [Au(d2pype)2]Cl increased intracellular reactive oxygen species (ROS) levels and induced caspase-3 activity leading to cell apoptosis through inhibiting both TrxR and glutathione peroxidase (Gpx) activity. Expression of the tumour suppresser gene TXNIP increased, while GPX1 and GPX4 expression, which are related to poor prognosis of lymphoma patients, decreased. Unlike SUDHL2 and SUDHL4 cells, which exhibited a decreased GSH/GSSG ratio after treatment, in KMH2 cells the ratio remained unchanged, while glutathione reductase and glutaredoxin expression increased. Since KMH2 cells were less sensitive to treatment with [Au(d2pype)2]Cl, the GSH system may play a role in protecting cells from apoptosis after TrxR inhibition. Overall, our study demonstrates that inhibition of TrxR represents a valid therapeutic approach for lymphoma.

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A fungus identified as Aspergillus aculeatus was used to biotransform genistein and glycosides to polyhydroxylated isoflavones. The strain was identified on the basis of colony morphology features and ITS rDNA sequence analysis. Phylogenetic tree was constructed to determine its taxonomic status. Genistein and glycosides were transformed by Aspergillus aculeatus to 5,7,8,4’- tetrahydroxyisoflavone. The chemical structure of the product was identified by high performance liquid chromatography(HPLC), liquid chromatography-mass spectrometry(LC/MS), Infrared spectroscopy (IR) and NMR spectrometer methods. The ITS rDNA sequence of the strain had 100% similarity with Aspergillus. Furthermore, it was ultimately identified as Aspergillus aculeatus. The metabolite of genistein and glycosides was identified as 5,7,8,4’-tetrahydroxyisoflavone. 120 mg 5,7,8,4’-tetrahydroxyisoflavone was made from 20 g fructus sophorae, which was bioconverted unconditionally by Aspergillus aculeatus for 96 h, and the purity was 96%. On the basis of the findings, Aspergillus aculeatus was a novel strain with specific ability to convert genistein and glycosides into 5,7,8,4’-tetrahydroxyisoflavone which had potential applications.