Background: This study aimed to investigate the molecular mechanism of Radix Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking.Methods: In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA–WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP–RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α.Results: Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, etc. Molecular docking results suggested that mairin was the most appropriate natural TNFis.Conclusion: Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.

Au ₂₅ nanoclusters as a self-therapeutic nanodrug significantly modulated macrophage polarization from M1 to M2 and could act as an inhibitor of thioredoxin reductase (TrxR), which induced ROS-mediated FLS apoptosis by breaking redox homeostasis.

The frequency stability is a key parameter to determine the performance of a micro-electro-mechanical (MEM) resonator. In this study, we utilized the mechanism of 1:2 internal resonance (IR) in a hermetically encapsulated beam resonator with a high Q-factor (>4000) to improve the frequency stability. When a MEM resonator is driven by a single-frequency actuation and conditions for IR are satisfied, two engaged modes are simultaneously resonated with their phases locked together through a strong and effective intermodal energy transfer. The increased inertia of these two active resonant modes leads to the frequency stabilization in both frequency outputs. In an open-loop experimental setting, we demonstrated that the IR achieved a six-fold improvement in the frequency stability. This paper reports the first implementation of IR in an encapsulated high-Q beam resonator.

Paeoniflorin (Pae), a water-soluble monoterpene glucoside, is the main effective component of total glucoside of paeony (TGP). Pae has a very low bioavailability (3.6%). The aim of this study was to investigate the effects of sex, food and disease status on the pharmacokinetics of paeoniflorin-6′-O-benzene sulfonate (acylated derivative of Pae, CP-25) and its primary metabolite (Pae, M1) after oral administration in the plasma of rats. A specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for rapid determination of CP-25 and Pae in rat plasma was developed and validated for the first time. The assay was validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects and stability. We found that CP-25 had a more extensive distribution in females than that in males, but no differences in M1 levels were found. Food intake could also increase the extent of absorption and decrease the rate of clearance for CP-25 and M1 after oral administration in rats. The disease status would decrease the absorption of CP-25 in rats. Comparing single-doing and multiple-dosing in an adjuvant arthritis (AA) model, the absorption of CP-25 and M1 improved with increasing dosage. Furthermore, during the period of multiple-dosing, CP-25 exhibited a better anti-inflammatory effect in AA rats and no obvious side effects occurred during the dosing period. Our findings provide the basis, and some guidelines, for further studies into the clinical application of CP-25.