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Asarinin is one of the main active chemical components isolated from Xixin, a Chinese medicine. To investigate the role of asarinin in rheumatoid arthritis (RA), the present study investigated the effect of an asarinin-medicated serum on human fibroblast-like synoviocytes in vitro. An asarinin-medicated serum was generated and analyzed by high-performance liquid chromatography. Fibroblast-like synoviocytes were isolated from patients with osteoarthritis and RA. The third generation of the rheumatoid synoviocytes was used in the experimental research and the third generation of osteoarthritic synoviocytes was used as control cells. Trypan blue staining was performed to detect the viability of RA synovial fibroblasts (RASFs). ELISA, reverse transcription-quantitative (RT-q) PCR and western blotting were also performed to detect the expression of various cytokines. Additionally, RT-qPCR was employed to detect Toll-like receptor (TLR) 2 and TLR4. The results revealed that medicated asarinin serum inhibited the viability of RASFs in a dose-and time-dependent manner. The serum also suppressed the expression of interleukin (IL)-17A, tumor necrosis factor-α, interferon-γ, IL-6, TLR2 and TLR4. The inhibitory effect of asarinin drug serum on RASFs may be achieved by inhibition of T helper cell (T h)1/T h 17 cytokines through suppression of TLR2 and TLR4.

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To study the role of asarinin on collagen-induced arthritis (CIA) and its treatment mechanism on dendritic cells (DCs) and T cells. Before the onset of arthritis, asarinin were given orally to CIA mouse. Macroscopic scoring and micrometer caliper measurement were used to assess arthritis. The occurrence of cartilage destruction and bone erosion were assessed by histology of knee. Sandwich enzyme-linked immunosorbent assay (ELISA) and PCR were used to assess the level of cytokines in hindpaw and arthritic joint. The CD11c MicroBeads were employed to isolate CD11c cells from the spleen. Quantitative PCR was used to determine DCs surface molecules of spleen. Macroscopic score and the frequency of arthritis were inhibited by asarinin. Swelling of hindpaws, inflammatory cell infiltration in the synovium, cartilage destruction, and bone erosion were delayed with asarinin. Asarinin treatment suppressed the expression of T helper type 1 (Th1) cytokines and increased the levels of Th2 cytokines (interleukin (IL)-10), transforming growth factor (TGF)-β and Foxp3 in the synovium and hindpaw, however T-bet mRNA levels in synovium decreased. Lower expression of toll-like receptor 9 (TLR9) and nuclear factor-kappaB (NF-κB) were found in DCs after asarinin treatment. There was no difference in the expression of intercellular cell adhesion molecule-1(ICAM-1), OX40-L, and 4-1BBL in spleen DCs between the asarinin group and model control group. Asarinin can treat CIA. TLR9/NF-κB pathway may be involved in the asarinin treatment of CIA by skewing the balance of Th1/Th2/regulatory T (Treg) to a Th2 type.

Summary This paper is devoted to the global stabilization via output feedback for a class of nonlinear systems with unknown relative degree, dynamics uncertainties, unknown control direction, and nonparametric uncertain nonlinearities. In particular, the unknown relative degree is without known upper bound, which renders us to research for a filter with varying dimension rather than the ones with over dimensions in the existing literature. In comparison with more popular but a bit stronger input‐to‐state stable or input‐to‐state practically stable requirement, only bounded‐input bounded‐state stable requirement is imposed on the dynamics uncertainties, which affect the systems in a persistent intensity rather than in a decaying one. In this paper, to compensate multiple serious system uncertainties and realize global output‐feedback stabilization, a design scheme via switching logic together with varying dimensional filter is developed. In this scheme, 2 switching sequences, which separately generate the gains of the controller and act as the varying dimensions of the filter, are designed to overcome unknown control direction, dynamics uncertainties and nonparametric uncertain nonlinearities, and unknown relative degree, respectively. A 2‐mass lumped‐parameter structure is provided to show the effectiveness of the proposed method in this paper.