Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The loss of dopaminergic (DAergic) neurons in the substantia nigra and the decrease of dopamine (DA) levels accelerate the process of PD. L-Ergothioneine (EGT) is a natural antioxidant derived from microorganisms, especially in edible mushrooms. EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients. Therefore, we speculated that EGT could ameliorate PD, and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺)-induced cell models. Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice. Mechanistically, we innovatively revealed that EGT is a key regulator of DJ-1. EGT restored DA levels by activating the DJ-1-Nuclear receptor-related factor 1(Nurr1) axis. Furthermore, it reduced reactive oxygen species (ROS) levels by regulating the DJ-1-Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which inhibited oxidative stress-induced DAergic neuronal apoptosis. Combined treatment with DJ-1-siRNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus, which significantly decreased the benefits of EGT. Taken together, our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.

Psoriasis is a chronic autoimmune disease featured by patches on the skin. It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features. Apigenin (API) is a natural flavonoid with anti-inflammatory and immunoregulatory properties. Therefore, we speculated that API can ameliorate psoriasis, and determined its effect on the development of psoriasis by using imiquimod (IMQ)-induced psoriasis mouse model. Our results showed that API attenuated IMQ-induced phenotypic changes, such as erythema, scaling and epidermal thickening, and improved splenic hyperplasia. Abnormal differentiation of immune cells was restored in API-treated mice. Mechanistically, we revealed that API is a key regulator of signal transducer activator of transcription 3 (STAT3). API regulated immune responses by reducing interleukin-23 (IL-23)/STAT3/IL-17A axis. Moreover, it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB (NF-κB) pathway. Furthermore, API reduced expression of inflammatory cytokines through inactivation of NF-κB. Taken together, our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.