Pien Tze Huang Alleviates Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Mice by Regulating Th1 and Th17 Cells

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by infiltrating inflammatory cells and demyelinating lesions, and T helper (Th) cells play critical roles in the pathogenesis of MS. There is still lack of effective treatments currently. Pien Tze Huang (PZH), a traditional Chinese medicine formula, has been proved to have anti-inflammatory, neuroprotective, and immunoregulatory effects. However, whether PZH can be used to treat MS is still obscure. This study aimed to investigate the possible therapeutic effect and the underlying action mechanism of PZH in relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) mice. Female SJL/J mice were immunized with myelin proteolipid protein 139–151 (PLP139−151) and pertussis toxin to establish RR-EAE model. Mice were then randomly divided into normal group, model group, PZH group and positive control group (fingolimod, FTY-720), and drugs were orally administered for 60 days from the day 10 after immunization. Sera of mice were collected for ELISA detection. Tissues of CNS were harvested for hematoxylin-eosin (H-E) and luxol fast blue (LFB) staining. Furthermore, Th1, Th17 cells and their related cytokines in the CNS were detected by flow cytometry and quantitative real-time PCR, respectively. Proteins involved in STAT and NF-κB signaling pathways were detected by western blot. The results showed that PZH-treated mice displayed mild or moderate clinical symptoms compared with untreated EAE mice that exhibited severe clinical symptoms. PZH remarkably reduced inflammatory cell infiltration and myelin damage in the CNS of EAE mice. It markedly down-regulated the levels of IFN-γ and IL-17A in sera of EAE mice. Moreover, PZH could reduce the percentages of Th1 and Th17 cells. It also suppressed the production of transcription factors ROR-γt and T-bet as well as the mRNA levels of their downstream pro-inflammatory cytokines, such as IFN-γ and IL-17A. Furthermore, PZH could inhibit the phosphorylation of some key proteins in the STAT and NF-κB signaling pathways. In conclusion, the study demonstrated that PZH had a therapeutic effect on RR-EAE mice, which was associated with the modulation effect on Th1 and Th17 cells.

Ghrelin Attenuates Neuroinflammation and Demyelination in Experimental Autoimmune Encephalomyelitis Involving NLRP3 Inflammasome Signaling Pathway and Pyroptosis

“…After being embedded in paraffin, the tissues were sectioned into 5-µm-thick slices for H&E or LFB staining to assess the degree of inflammatory cell infiltration and spinal demyelination, respectively, following the manufacturers’ protocols. Inflammatory infiltrations and demyelination were evaluated as described in a previous study, and the final score of each rat was averaged from three different histologic sections (Qiu et al, 2018). Stained sections were observed under a Nikon 300 microscope.…”

The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing—Remitting Multiple Sclerosis Mouse Model

“…PowerUp™ SYBR ® Green (Thermo Fisher Scientific, Waltham, MA, USA) Master Mix (2×) reagents were used according to the manufacturer's recommendations. Primers were bought from SIGMA-Aldrich (St. Louis, MO, USA): for S100B and inducible nitric oxide synthase (iNOS) after design by NCBI Primer-Blast program (https://www.ncbi.nlm.nih.gov/tools/primer-blast), while the other oligos were deduced from literature [20][21][22][23][24]. Each gene target quantification reaction was performed separately with the respective primer sets (Table S1).…”

Pien Tze Huang alleviate the joint inflammation in collagen-induced arthritis mice

“…Z35020243). The drug samples were identified and characterized by HPLC-MS/TOF as our previous publication [12]. Stock solution of PZH was prepared by dissolving the PZH powder in purified water and the sample was fully blended again prior to use.…”

“…It has been used in China and Southeast Asia for centuries as a folk remedy for various inflammation related diseases, such as hepatitis. It was proved that PZH exerted anti-inflammatory effect by regulating the percentage of Th1 and Th17 cells, reducing the expression of IL-17, IL-23 and IFN-γ and regulating NF-κB and STAT signaling pathways in inflammatory model animals [11,12]. Recently, some medicinal components of Notoginseng Radix et Rhizoma have been reported to have remarkable effect in treating mice or rats with collagen-induced arthritis (CIA), a classical RA animal model [13,14].…”