Ta-Xi-San Suppresses Atopic Dermatitis Involved in Multitarget Mechanism Using Experimental and Network Pharmacology Analysis.

Atopic dermatitis (AD) is a relapsing and chronic skin inflammation with a common incidence worldwide. Ta-Xi-San (TXS) is a Chinese herbal formula usually used for atopic dermatitis in clinic; however, its active compounds and mechanisms of action are still unclear. Our study was designed to reveal the pharmacological activities, the active compounds, and the pharmacological mechanisms of TXS for atopic dermatitis. Mice were induced by 2,4-dinitrocluorobenzene (DNCB) to build atopic dermatitis model. The pathological evaluation, enzyme-linked immunosorbent assay (ELISA), and hematoxylin and eosin (H&E) assay were performed. The UPLC-Q-Exactive-MSE and network pharmacology analysis were performed to explore active ingredients and therapeutic mechanisms of TXS. TXS treatment decreased levels of immunoglobulin E (IgE), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α) in serum induced by DNCB. TXS reduced scratching behavior and alleviated inflammatory pathology of skin and ear. Meanwhile, TXS decreased the spleen index and increased spleen index. The UPLC-Q-Exactive-MSE results showed that 65 compounds of TXS were detected and 337 targets were fished. We collected 1371 AD disease targets, and the compound-target gene network reveled that the top 3 active ingredients were (-)-epigallocatechin gallate, apigenin, and esculetin, and the core target genes were PTGS2, PTGS1, and HSP90AA1. The KEGG pathway and GO analysis showed that TXS remedied atopic dermatitis via PI3K-Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and Toll-like receptor (TLR) signaling pathway with the regulation of inflammatory response and transcription. Further, we found that the targets of PTGS2 and HSP90AA1 were both elevated in ears and skin of AD model mouse; however, TXS decreased the elevated expressions of PTGS2 and HSP90AA1. Our study revealed that TXS ameliorated AD based on (-)-epigallocatechin gallate, apigenin, and esculetin via targeting PTGS2 and HSP90AA1.

Intelligent hydrogel with both redox and thermo-response based on cellulose nanofiber for controlled drug delivery.

The purpose of this study is to develop a hydrogel with temperature and redox response to control drug delivery. However, the strength of temperature sensitive N-isopropylacrylamide (NIPAM) hydrogel is weak. Therefore, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized cellulose nanofiber (CNF) is introduced to improve this problem. The compressive strength of hydrogels increased by 360% after CNF addition. Meanwhile, N,N'-bis(acryloyl)cystamine (BACy) is introduced into the hydrogels as a cross-linker, imparting redox responsive properties to the hydrogels. Tumor therapeutic drugs are used as model drugs for in vitro release studies. The drug release rate of hydrogel is regulated by temperature and reducing environment. The maximum cumulative release rate of doxorubicin (DOX) is 39.56%, and the Berberine (BBR) is 99.50% after 60 h. The swelling and transparency of hydrogels showed dramatic changes in the range of 30-40 °C. Cytotoxicity experiments demonstrated that the hydrogel had almost no cytotoxicity.

Preparation and properties of a highly elastic galactomannan- poly(acrylamide- N, N-bis (acryloyl) cysteamine) hydrogel with reductive stimuli-responsive degradable properties.

An oxidation-reduction responsive degradable highly elastic galactomannan hydrogel was synthesized from galactomannan (GA), N,N-bis (acryloyl) cysteamine (BAC) and acrylamide by grafting polymerization in aqueous solution. The microstructure, degradability and mechanical properties of the hydrogels were emphatically investigated using Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), ultraviolet spectroscopy and differential scanning calorimetry (DSC). The mechanical properties of hydrogels can be improved by adjusting the content of GA. Continuous cyclic compression tests showed that the hydrogel did not rupture under 60 %,70 %,80 % strain and quickly recovered to its original shape. The degradation rate and drug release rate of hydrogel can be adjusted by the concentration of the reductant and the reduction time. These hydrogels broaden the scope of application of GA and can be tuned with a broad range of mechanical, degradation and release properties and therefore hold potential applications in drug carriers, tissue engineering scaffolds, extracellular matrix and other fields.

Study on the physicochemical properties and anti-inflammatory effects of paeonol in rats with TNBS-induced ulcerative colitis.

Paeonol, an active component from Paeonia suffruticosa Andr., has a variety of biological activities, such as vascular endothelial cell protection, anti-oxidation, and anti-inflammation. The aim of this study was to investigate the basic physicochemical properties of paeonol, including solubility, oil-water partition coefficient, and permeability. Then evaluated the anti-inflammatory effects of paeonol were evaluated on 2,4,6-trinitrobenzenesulfonic acid-induced ulcerative colitis in rats. The rats were divided randomly into 6 groups, namely, normal, model, paeonol-treated (100, 200, and 400mg/kg), and positive. Each group had 10 rats. Inhibition effects were evaluated by the disease activity index (DAI), colon weight/length ratio, as well as macroscopical and histological evaluations. Serum interleukin (IL)-17, IL-6 and transforming growth factor beta 1 (TGF-ß1) levels were determined by enzyme-linked immunosorbent assay. The solubility and oil-water partition coefficient of paeonol in different phosphate buffer solutions were 284.06-598.23 and 461.97-981.17µg/mL, respectively. The effective passive permeability value Pe was 23.49×10-6cm/s. In terms of anti-inflammatory results, compared with the model group, treatment with 200 and 400mg/kg doses of paeonol had significantly decreased DAI, colon weight/length ratio, and macroscopic and histopathological scores. Furthermore, the serum levels of IL-17 and IL-6 were significantly reduced, whereas the TGF-ß1 level was increased in the two paeonol-treated groups (medium- and high-dose group). Therefore, paeonol had poor water solubility, but oral absorption was good. In addition, paeonol had therapeutic effects on ulcerative colitis, and the therapeutic efficacy was dose dependent. The results presented in this study provide evidence for the development of a novel therapeutic agent in the treatment of UC. However, whether this agent could have therapeutic benefit or adverse effects in human IBD remains to be fully explored.