Abstract
Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN)-striatum circuit, which is associated with glial activation and consequent chronic neuroinflammation. Optimized Yinxieling Formula (OYF) is a Chinese medicine that exerts therapeutical effect and antiinflammation property on psoriasis. Our previous study has proven that pretreatment with OYF could regulate glia-mediated inflammation in an acute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Given that PD is a chronic degeneration disorder, this study applied another PD animal model induced by striatal injection of 6-hydroxydopamine (6-OHDA) to mimic the progressive damage of the SN-striatum dopamine system in rats. The OYF was administrated in the manner of pretreatment plus treatment. The effects of the OYF on motor behaviors were assessed with the apomorphine-induced rotation test and adjusting steps test. To confirm the effect of OYF on dopaminergic neurons and glia activation in this model, we analyzed the expression of tyrosine hydroxylase (TH) and glia markers, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP) in the SN region of the rat PD model. Inflammation-associated factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were further evaluated in this model and in interferon-γ- (INF-γ-) induced murine macrophages RAW264.7 cells. The results from the in vivo study showed that OYF reversed the motor behavioral dysfunction in 6-OHDA-induced PD rats, upregulated the TH expression, decreased the immunoreactivity of Iba-1 and GFAP, and downregulated the mRNA levels of TNF-α and COX-2. The OYF also trended to decrease the mRNA levels of IL-1β and iNOS in vivo. The results from the in vitro study showed that OYF significantly decreased the mRNA levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2. Therefore, this study suggests that OYF exerts antiinflammatory effects, which might be related to the protection of dopaminergic neurons in 6-OHDA-induced chronic neurotoxicity.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disorder and is characterized by dopaminergic neurons damage in the substantia nigra (SN) and dopamine (DA) deficiency in the striatum, which could result in abnormal motor function [1, 2]
Many inflammatory molecules were found to be Evidence-Based Complementary and Alternative Medicine involved in PD, including IL-1β, inducible nitric oxide synthase, and cyclooxygenase-2 (COX-2) [5]. e expression of iNOS could lead to the production and release of nitric oxide (NO), which may mediate neurotoxicity and be harmful to dopaminergic neurons [6, 7]. ese proinflammatory cytokines or neurotoxic substances could be induced by activation of astrocytes and microglia [8, 9]
Optimized Yinxieling Formula (OYF) is a Chinese medicine compound modified from the Yinxieling formula, which has been proven to have therapeutical effect and antiinflammation property on psoriasis [10]. e OYF consists of Curcuma zedoaria, Sarcandra glabra, dark plum fruit, Rhizoma Smilacis Glabrae, Lithospermum erythrorhizon, Paeonia lactiflora, and Glycyrrhiza uralensis [11]
Summary
Parkinson’s disease (PD) is a common neurodegenerative disorder and is characterized by dopaminergic neurons damage in the substantia nigra (SN) and dopamine (DA) deficiency in the striatum (receive SN dopaminergic nerve terminals projection), which could result in abnormal motor function [1, 2]. E underlying mechanisms might be through downregulating the keratinocyte cyclin B2 or nuclear factor-kappa B (NF-κB), inhibiting cell proliferation or the release of the inflammatory cytokine and chemokine in the keratinocyte [13, 14]. Taken together, these studies suggest that OYF may have antiinflammation property. Since the SN-striatum DA pathway dysfunction is associated with PD pathology, in this study, we further applied striatal injection of the 6-hydroxydopamine- (6OHDA-) induced rat model of PD, in which the loss of the SNstriatum DA pathway is progressive to evaluate the effects of OYF on motor behavioral alterations in PD. We hypothesized that the inflammatory mechanism might be involved in the effects of OYF. us, IFN-c-induced RAW264.7 was used as an inflammatory model in vitro
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