Reactive oxygen species and nitric oxide scavenging nanoparticles alleviating rheumatoid arthritis through adjusting the seeds and growing soils

Normalizing inflamed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inflammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol (Not@BR/oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.

Study on Effect of Notopterol on Dextran Sulfate Sodium-induced Colitis in Mice / 胃肠病学

Background; Immunological dysfunction plays a key role in the pathogenesis of inflammatory bowel disease (I B D). Notopterol is the main ingredient of the traditional Chinese herb medicine Notopterygium ineisum Ting ex H. T. Chang and has anti-inflammatory effect. Aims; To explore the effect of notopterol on dextran sulfate sodium (DSS)-induced colitis in mice. Methods; C57BL/6 mice were randomly divided into normal group, negative control group, model group and notopterol group. Mice in model group and notopterol group were treated with 2% DSS to induce colitis. Mice in negative control group and notopterol group were injected intraperitoneally with notopterol 40 mg/kg, and mice in normal group and model group were injected intraperitoneally with 0. 9% NaCl solution. Mice were sacrificed 10 days later, and disease activity index (DAI) score, colon length and histopathologieal score were determined. The levels of TNF-α, IL-1β, IL-6, IL-17A were assessed by ELISA. The mRNA expressions of IL-17A, RORγt were detected by quantitative PCR. Results; Compared with the normal group, DAI score, histopathologieal score, levels of TNF-α, IL-1β, IL-6, IL-17A, mRNA expressions of IL-17A and RORγt in model group were significantly increased (P < 0. 0 1), and colon length were significantly shortened (P < 0. 0 1). Compared with the model group, notopterol significantly reduced DAI score and histopathologieal score (P<0.01), downregulated levels of TNF-α, IL-1β, IL-6, IL-17A (P<0.01), inhibited the mRNA expressions of IL-17A, ROR-γt (P < 0. 0 1), and greatly recovered colon length (P < 0. 0 1). Conclusions; Notopterol has protective effects on DSS-induced colitis in mice. The mechanism may be related to reducing the secretion of pro-inflammatory cytokines and inhibiting the function and differentiation of Thl7 cells.

Comparison on release and transdermal behavior in vitro between Dinggui Gel Paste and Dinggui Huoluo Rubber Patch / 中草药

Objective: To compare the release and transdermal behavior in vitro between Dinggui Huoluo Rubber Patch (DHRP) and Dinggui Gel Paste (DGP) which is the improved form. Methods: Microporous filter membrane or Strat-M membrane and advanced Franz diffusion cell were chosen in the release and transdermal experiment in vitro. The content of notopterol, the active component of the key herb Notopterygium incisum in the preparation, was quantitatively determined by HPLC method to determine the release rate, penetration quantity, and penetration rate of the two forms. Results: The penetration formula of DGP was Ln = 9.208 t-18.50, r = 0.948. The in vitro cumulative release rate, penetration quantity, and penetration rate were respectively 85.34%, 0.661 8 mg/g, and 65.67%. The penetration formula of DHRP was Ln = 4.285 t-6.704, r = 0.977. The in vitro cumulative release rate, penetration quantity, and penetration rate were respectively 67.87%, 0.181 6 mg/g, and 31.35%. Conclusion: The transdermal behavior of DGP is obviously better than that of DHRP while its quantity and the rate of penetration and release are all better than those of rubber patch. Meanwhile the gel paste is less sensitized and more convenient to use.

Effectiveness analysis of determining the content of notopterol and isoimperatorin in notopterygium / 重庆医学

Objective To establish the effect of determining the content of notopterol and isoimperatorin in notopterygium from different habitat and harvest time by HPLC method .Methods HPLC instrument was used ,Waters symmetry C18(4 .6 mm × 250 mm ,5 μm) was adopted with a mobile phase of acetonitrile‐water (45∶55) ,the separation was carried out at a flow rate of 1 mL/min ,column temperature was 30 ℃ and the detection wavelength was 310 nm .Results Notopterol and isoimperatorin showed good linearity in the ranges of 0 .240 8-1 .505 0 μg and 0 .117 6-0 .735 0 μg with average recoveries rate (n=6) of 0 .98% and 1 .42%respectively .The content of notopterol and isoimperatorin in crude drugs of notopterygium from different habitat marked differ‐ence ,and harvest period and growth years made effect to content of two components .Conclusion HPLC method is easy and fast , and can be used as a basis for confirming the best habitat and harvest period of notopterygium .