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.

There are several health and physiological benefits of QCT administration including cardioprotective, anti-diabetic, anticarcinogenic, antioxidant, anti-inflammatory, anti-apoptotic and antimicrobial effects. 1,3,4 For the microorganism, quercetin has shown antibacterial, anti-biofilm and microbiota-regulating properties. Quercetin could inhibit the growth of planktonic Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Actinomyces viscosus, Fusobacteriumnucleatum, and Actinomyces naeslundii and Helicobacter pylori. [5][6][7] When quercetin was used in combination with antibiotics including amoxicillin, ampicillin, cephradine, ceftriaxone, imipenem or methicillin, they were found to increase each other's activity against Staphylococcus aureus. 8 Aside from planktonic bacteria, quercetin has also been reported to inhibit biofilm development for multiple bacteria such as Enterococcus faecalis, Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Pseudomonas aeruginosa. Bacterial biofilm is multicellular aggregates enclosed in a self-created biopolymer matrix and could enable these microorganisms to evade host.Qayyum et al demonstrated that quercetin (256mg/L) could inhibit 95% biofilm formation of E. faecalis MTCC 2729 through crystal violet assay. The anti-biofilm effect of quercetin was confirmed by scanning electron microscopy (SEM) and CLSM. 9 As far as Gram-negative bacterium Pseudomonas aeruginosa, Ouyang et al. reported quercetin is an effective inhibitor of quorum sensing, biofilm formation and virulence factors at a low concentration (16mg/L).Base on the effects on these microorganisms, their biofilm and related factors, quercetin may influence the gut microbiota which is an ecosystem consisted of an estimated 10-100 trillion microorganisms, including bacteria, fungi, archaea and viruses and exerts diverse physiological functions, such as modulation of immune system, regulation of the gut barrier integrity and biosynthesis of vitamins. 10 Zhao et al demonstrated that combination of quercetin and resveratrol could reduce obesity in high-fat diet-fed rats by modulation of gut microbiota composition, decreasing the abundance of Firmicutes, Desulfovibrionaceae, Acidaminococcaceae, Coriobacteriaceae, Bilophila, Lachnospiraceae and its genus Lachnoclostridium, which were reported to be potentially related to diet-induced obesity, increasing the abundance of Bacteroidales, Christensenellaceae, Akkermansia, Ruminococcaceae.Akkermansiahas been considered as a next-generation of beneficial probiotic and to be associated with metabolic disorders. 11,12 This work was supported by Chongqing Basic and Frontier Research project (No. cstc2018jcyjAX0652) and Chongqing Health