BackgroundMounting evidence shows that urate may become a biomarker of Parkinson's disease (PD) diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood.ResultsIn this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5) against 6-hydroxydopamine (6-OHDA)- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1) expression. In addition, urate markedly up-regulated the transcription and protein expression of γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC) and heme oxygenase-1 (HO-1), both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment.ConclusionOur findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses.

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Pien Tze Huang (PZH) is a Chinese patent medicine with anti-inflammatory and immunomodulatory effects. However, whether PZH could be used in RA therapy is still unknown. Therefore, this study aimed to explore the therapeutic effect and the potential mechanism of PZH on collagen-induced arthritis (CIA) mice. Methods: Male DBA/1J mice were used to establish an animal model of CIA and then treated with different doses of PZH for 4 weeks. The therapeutic effect of PZH on CIA mice was evaluated by arthritis score, pathological staining, and detecting the levels of inflammatory factors in serum and joints. To investigate its possible mechanism, the activity of NF-κB signaling pathway, NLRP3 inflammasome and the level of A20 were detected. Results: The results showed that PZH could alleviate the erythema and swelling of hind paws of CIA mice, improve the pathological conditions of joint and decrease the production of IL-1β, IL-6 and IL-17 in serum and joints. Furthermore, PZH could significantly inhibit the activity of NF-κB signaling pathway and NLRP3 inflammasome in the ankle joint of CIA mice compared with the model group. It also increased the level of A20 in the ankle joint of CIA mice. Conclusion: This study indicated that PZH could alleviate the joint inflammation of CIA mice, and the mechanism might be related to the regulation of NF-κB signaling pathway and NLRP3 inflammasome.

Bone destruction is an important pathological feature of rheumatoid arthritis (RA), which finally leads to the serious decline of life quality in RA patients. Bone metabolism imbalance is the principal factor of bone destruction in RA, which is manifested by excessive osteoclast-mediated bone resorption and inadequate osteoblast-mediated bone formation. Although current drugs alleviate the process of bone destruction to a certain extent, there are still many deficiencies. Recent studies have shown that traditional Chinese medicine (TCM) could effectively suppress bone destruction of RA. Some bioactive compounds from TCM have shown good effect on inhibiting osteoclast differentiation and promoting osteoblast proliferation. This article reviews the research progress of bioactive compounds exacted from TCM in inhibiting bone destruction of RA, so as to provide references for further clinical and scientific research.