Curative Anti‐Inflammatory Properties of Chinese Optimized Yinxieling Formula in Models of Parkinson’s Disease

Abstract

Parkinson's disease (PD) is marked by the progressive degeneration of dopaminergic neurons (DAN) accompanied by glial activation. Thus, inhibiting glial activation that occurs during this disease could be an effective method for treating PD. Optimized Yinxieling Formula (OYF), a Chinese medicinal formula, which is used to efficiently treat autoimmune disease psoriasis, has been proved to display potential immunomodulatory effects in inflammation-associated diseases. This study assessed the therapeutic benefits of OYF on glial-mediated neuroinflammation and neuroprotection in PD models in vitro and in vivo. First, the results showed that OYF significantly suppresses LPS-induced proinflammatory cytokine secretion and attenuates the overall inflammatory responses in BV-2 cells. Second, in vivo studies confirm that while the validity of our MPTP-induced PD mouse models possesses activated glia and significant neurobehavioral dysfunction, pretreatment with OYF prevents glial activation and ameliorates movement dysfunction in the MPTP-induced PD mouse models as evaluated by the pole and rotarod tests. Third, transcriptomic analyses were carried out to reveal the underlying molecular mechanism of the OYF treatment. Sixteen pathways were significantly upregulated in the OYF-treated PD model mice, including the cytokine-cytokine receptor interaction, cell adhesion molecules, coagulation, and complement cascades. Fifteen pathways were significantly downregulated in the OYF-treated PD model mice, such as the natural killer cell mediated cytotoxicity, hematopoietic cell lineage, phagosome, and others. These pathways share direct or indirect features of immunomodulation, suggesting that the physiological effects of OYF involve key roles of immune and inflammation regulations. Therefore, we prove that OYF is a useful immunomodulatory formula in developing prevention and treatment methods for neurodegenerative disease PD.

Neuroprotective Effect of Optimized Yinxieling Formula in 6-OHDA-Induced Chronic Model of Parkinson’s Disease through the Inflammation Pathway

“…Evidence-Based Complementary and Alternative Medicine Furthermore, in the in vitro experiment, IFN-c stimulation upregulated TNF-α, IL-1β, and IL-6 mRNA levels in RAW264.7 cells, whereas a high dose of OYFCS reversed the elevated levels ( Figure 5). ese results were similar to our previous study in the MPTP-induced mice model and in LPSinduced BV-2 cells [15]. Taken together, these results suggest that OYF exerts an antiinflammation effect in the PD model.…”

“…Other population-based cohort studies also showed that psoriasis patients had significantly higher risk of developing PD, suggesting a potential relation between PD and psoriasis [28]. Given that inflammation is the common pathology of PD and psoriasis and that the OYF had antiinflammation property in treating psoriasis, our previous study investigated the effects of OYF in the MPTP-induced PD mouse model and found that OYF attenuated the loss of dopaminergic neurons in SN and alleviated the inflammatory response [15]. In addition to the MPTP-induced model, there are other commonly used animal models of PD that employ toxins, including 6-OHDA, which is similar to DA in structure and can specifically kill dopaminergic neurons and their terminals [16].…”

“…Taken together, these studies suggest that OYF may have antiinflammation property. Given that neuroinflammation plays a crucial role in PD pathology [5], we previously applied the 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine-(MPTP-) induced mice model to study the effect of OYF in the PD model and found that OYF attenuated SN dopaminergic neuron damage and exhibited antiinflammatory effects [15]. ough the MPTPinduced model is widely used to mimic the PD hallmarks, such as tyrosine hydroxylase (TH, a key enzyme in the DA biosynthesis) immunoreactive neuron loss, this process is acute and may be insufficient for permanent impairment of the SNstriatum pathway [16].…”

Psoriasis and neurodegenerative diseases—a review

“…Therefore, its preventive and therapeutic effects have been observed, among others, in psoriasis and NDs, including PD, AD, and ALS. Wei et al assessed the efficacy of the optimized yinxieling formula (OYF), which is a Chinese medicinal formula successfully used in psoriasis therapy, in PD (Wei et al, 2018 ). They found beneficial OYF influence on the suppression of inflammation and immunomodulatory properties and suggested it could be useful also in PD (Wei et al, 2018 ).…”

Traditional Chinese medicine-based neurorestorative therapy for Alzheimer’s and Parkinson’s disease

“…Consequently, the excessive activation of proinflammatory phenotypes caused by microglia can lead to chronic inflammation and consequently accelerate oxidative stress and apoptosis induced death oftheneurons. An in vivo study showed that optimized Yinxieling formula inhibited the activation of microglia and suppressed the secretion of proinflammatory cytokines in the MPTP-induced PD mouse models via down-regulation of the NF-κB signaling pathway, which protected the DA neurons from immune-mediated death [21]. Similar effects were found in an Aβ1-42-induced AD mouse model treated with an A. oxyphylla-Schisandra chinensis herbal formulation and an LPS-induced AD mouse model treated with Nootkatone derived from A. oxyphylla [29,31].…”