Neuroprotective Effect of Dioscin against Parkinson’s Disease via Adjusting Dual-Specificity Phosphatase 6 (DUSP6)-Mediated Oxidative Stress

Abstract

Exploration of lead compounds against Parkinson’s disease (PD), a neurodegenerative disease, is of great important. Dioscin, a bioactive natural product, shows various pharmacological effects. However, the activities and mechanisms of dioscin against PD have not been well investigated. In this study, the tests on 6-hydroxydopamine (6-OHDA)-induced PC12 cells and rats were carried out. The results showed that dioscin dramatically improved cell viability, decreased reactive oxygen species (ROS) levels, improved motor behavior and tyrosine hydroxylase(TH) levels and restored the levels of glutathione (GSH) and malondialdehyde (MDA) in rats. Mechanism investigation showed that dioscin not only markedly increased the expression level of dual- specificity phosphatase 6 (DUSP6) by 1.87-fold in cells and 2.56-fold in rats, and decreased phospho-extracellular regulated protein kinases (p-ERK) level by 2.12-fold in cells and 2.34-fold in rats, but also increased the levels of nuclear factor erythroid2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), superoxide dismutase (SOD) and decreased the levels of kelch-1ike ECH-associated protein l (Keap1) in vitro and in vivo. Furthermore, DUSP6 siRNA transfection experiment in PC12 cells validated the protective effects of dioscin against PD via regulating DUSP6 to adjust the Keap1/Nrf2 pathway. Our data supported that dioscin has protection against PD in regulating oxidative stress via DUSP6 signal, which should be considered as an efficient candidate for the treatment of PD in the future.

Effects of Organophosphate-Degrading Bacteria on the Plant Biomass, Active Medicinal Components, and Soil Phosphorus Levels of Paris polyphylla var. yunnanensis

“…yunnanensis are primarily steroidal saponins that have anti-inflammatory and anti-tumor effects [ 26 , 27 , 28 , 29 , 30 , 31 ]. The 2020 edition of the Chinese Pharmacopoeia includes polyphyllin I, II, and VII as quality control indicators [ 2 ], and studies have also shown that polyphyllin H has hemostatic effects [ 32 ], dioscin has strong immunomodulatory effects [ 33 , 34 , 35 ], and pseudoprotodioscin can reduce the gene expression regarding the synthesis of cholesterol and triglycerides [ 36 ]. In addition, Gao et al [ 37 ] showed that the saponins of polyphyllin can scavenge reactive oxygen species and significantly inhibit lipid peroxidation.…”

TRIM11 expression levels was downregulated and prevents ferroptosis of cardiomyocyte by Dusp6 in acute myocardial infarction

“…DUSPs can participate in various cellular functions by regulating the MAPK pathway, thereby playing a role in the regulation of different diseases [22,23]. DUSP6 (dual-specificity phosphatase 6) is a member of the DUSP family that specifically targets the extracellular signal-regulated kinases (ERK) pathway, and it has a very high substrate specificity and dephosphorylation of the ERK pathway [24]. According to the literature, DUSP6 was confirmed to be negatively correlated with the level of Kirsten rat sarcoma viral oncogene homolog expression in experiments related to human non-small cell lung cancer (NSCLC).…”