A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of ß-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

Ligand fishing based on tubular microchannel modified with monoamine oxidase B for screening of the enzyme's inhibitors from Crocus sativus and Edgeworthia gardneri.

A novel strategy of performing ligand fishing with enzyme-modified open tubular microchannel was proposed for screening bioactive components present in medicinal plants. Monoamine oxidase B was immobilized onto the surface of the microchannel for the first time to specifically extract its ligands when the plant's extracts solution flows through the channel. The thermal and the storage stability of immobilized monoamine oxidase B were significantly enhanced after immobilization. Crocin I and Ⅱ were extracted from Crocus sativus, and tiliroside was extracted from Edgeworthia gardneri. All the three compounds were inhibitors of the enzyme with the half-maximal inhibitory concentration values of 26.70 ±â€¯0.91, 19.88 ±â€¯2.78, and 15.65 ± 0.85 µM, respectively. The enzyme inhibition kinetics and molecular docking were investigated. This is the first report on the inhibitory effects of tiliroside and crocin Ⅱ. The novel ligand fishing method proposed in this work possesses advantages of rapidness, high efficiency, and tiny sample consumption compared to routine ligand fishing, with promising potential for screening active natural products in complex mixtures.

Fast screening of tyrosinase inhibitors from traditional Chinese medicinal plants by ligand fishing in combination with in situ fluorescent assay.

A simple and rapid method for screening of tyrosinase (TYR) inhibitors present in traditional Chinese medicines (TCMs) was developed by combining ligand fishing and the fluorescent enzymatic assay based on dopamine-functionalized carbon quantum dots (CQDs-Dopa). Ligands of the enzyme present in the TCM extractions were firstly adsorbed on the enzyme-modified magnetic beads, and then the beads were magnetically separated and subjected directly to the CQDs-Dopa-based fluorescent assay. Finally, compounds were desorbed from the "active" beads and identified with ultra-performance liquid chromatography-triple quadrupole mass spectrometry. A known natural TYR inhibitor quercetin was selected to assess the feasibility and quantification performance of this method, and good linearity in the range of 0.01-0.16 mM (R2 = 0.992) with a low detection limit of 0.004 mM was obtained. This method was then applied to screen TYR inhibitors present in Scutellaria baicalensis and Sophora flavescens. Six TYR inhibitors including baicalin (1), baicalein (2), wogonin (3), oroxylin A (4), kurarinone (5), and sophoraflavanone G (6) were found, among which 1-4 were firstly discovered in this work. This is the first report on the in situ assessment of the target compounds obtained by ligand fishing in the form of a mixture, which exhibited the combined advantages of specific extraction ability of ligand fishing and the high sensitivity of CQDs-based fluorescent assay, showing great potential for fast screening of enzyme inhibitors from TCMs.