Fungal Melanins as Potential Reactive Oxygen Species-Scavenging Neuroprotective Agents

Oxidative stress is strongly associated with neuronal damage in neurodegenerative diseases, such as Parkinson's disease (PD). Fungal melanins are remarkable free radical scavengers; however, their capacity to protect neurons from reactive oxygen species (ROS)-induced damage remains understudied. This research evaluated the neuroprotective effects of fungal melanins and their arginine-modified counterparts on SH-SY5Y cells against neurotoxins, as well as their impact on ROS levels. Exposure to 0.6 mM H₂O₂ or 1 mM MPP⁺ markedly elevated ROS levels and reduced cell viability to approximately 56% and 60%, respectively. At 10 μg/mL, melanins from Apioperdon pyriforme, Russula nigricans, and Xylaria nigripes significantly protected cells against H₂O₂ cytotoxicity, whereas arginine-modified melanin from the skin of Scleroderma sinnamariense significantly attenuated MPP⁺ cytotoxicity. Further dose-dependent evaluation revealed that melanin from A. pyriforme (10-12 μg/mL) displayed activity comparable to the positive control (164 μg/mL N-Acetylcysteine (NAC)) against H₂O₂ by increasing cell viability up to 90%. Similarly, arginine-modified melanin from S. sinnamariense (6-10 μg/mL) and NAC showed a comparable protective effect against MPP⁺, boosting cell viability up to 80%. Both samples suppressed ROS to levels comparable to, or lower than, the untreated control. Melanin from A. pyriforme is a promising candidate for further research into complementary therapies for PD.