Xiaoqinglong decoction improves allergic rhinitis by inhibiting NLRP3-mediated pyroptosis in BALB/C mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. AIM OF THE STUDY: NLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD. MATERIALS AND METHODS: BALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting. RESULTS: XQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1ß and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome. CONCLUSIONS: The representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.

Prostate-Specific Membrane Antigen-1-Mediated Au@SiO2@Au Core-Shell Nanoparticles: Targeting Prostate Cancer to Enhance Photothermal Therapy and Fluorescence Imaging.

The advantages of deep tissue penetration and the high spatial accuracy of photothermal therapy have been widely studied. Gold, as a photothermal material, has received particular attention. Different sizes and shapes of gold have been studied and characterized for their varying photothermal properties. The core-shell structure of gold nanoparticles and silica enhances the photothermal conversion through the coupling effect between gold clusters on the material's surface. With excellent photothermal conversion performance, the core-shell nanoparticles can quickly reach 40 °C in 200 s under the irradiation of 808 nm, 1.5 W·cm-2. The highest conversion temperature of these nanoparticles is 56 °C, and the photothermal conversion rate is 45%. In vitro cell experiments displayed that NPs with targeted function can efficiently aggregate in prostate cancer cells and effectively kill cells. In vitro experiments showed that the tumor cells of mice after photothermal treatment completely disappeared after 15 days, which fully demonstrated the potential of the nanoparticles for targeted photothermal therapy.

Recent advances on synthesis and biological activities of aurones.

Aurones are naturally occurring structural isomerides of flavones that have diverse bioactivities including antiviral, antibacterial, antifungal, anti-inflammatory, antitumor, antimalarial, antioxidant, neuropharmacological activities and so on. They constitute an important class of pharmacologically active scaffolds that exhibit multiple biological activities via diverse mechanisms. This review article provides an update on the recent advances (2013-2020.4) in the synthesis and biological activities of these derivatives. In the cases where sufficient information is available, some important structure-activity relationships (SAR) of their biological activities were presented, and on the strength of our expertise in medicinal chemistry and careful analysis of the recent literature, for the potential of aurones as medicinal drugs is proposed.

Near-infrared photothermal liposomal nanoantagonists for amplified cancer photodynamic therapy.

Photodynamic therapy (PDT) has been demonstrated to be a promising strategy for the treatment of cancer, while its therapeutic efficacy is often compromised due to excessive concentrations of glutathione (GSH) as a reactive oxygen species (ROS) scavenger in cancer cells. Herein, we report the development of near-infrared (NIR) photothermal liposomal nanoantagonists (PLNAs) for amplified PDT through through the reduction of intracellular GSH biosynthesis. Such PLNAs were constructed via encapsulating a photosensitizer, indocyanine green (ICG) and a GSH synthesis antagonist, l-buthionine sulfoximine (BSO) into a thermal responsive liposome. Under NIR laser irradiation at 808 nm, PLNAs generate mild heat via a ICG-mediated photothermal conversion effect, which leads to the destruction of thermal responsive liposomes for a controlled release of BSO in a tumor microenvironment, ultimately reducing GSH levels. This amplifies intracellular oxidative stresses and thus synergizes with PDT to afford an enhanced therapeutic efficacy. Both in vitro and in vivo data verify that PLNA-mediated phototherapy has an at least 2-fold higher efficacy in killing cancer cells and inhibiting tumor growth compared to sole PDT. This study thus demonstrates a NIR photothermal drug delivery nanosystem for amplified photomedicine.

Bioactivity-guided cut countercurrent chromatography for isolation of lysine-specific demethylase 1 inhibitors from Scutellaria baicalensis Georgi.

Countercurrent chromatography (CCC) has gradually become a widely used method for preparative separation of bioactive natural molecules. These molecules generally contain distinct scaffolds and characteristics that cannot be readily isolated from plants. While one-dimensional CCC is typically used for the initial purification with insufficiently resolved peaks after locating bioactive components, two-dimensional (2D) or multi-dimensional CCC strategies are employed to improve the resolution of peaks. However, these methods usually present certain disadvantages, such as complicated procedures and increased time consumption, experimental costs, and equipment requirements. Here, a bioactivity-guided cut CCC strategy was established to isolate lysine-specific demethylase 1 (LSD1) inhibitors from Scutellaria baicalensis Georgi. Gradient-elution CCC coupled with real-time detection of LSD1 inhibition by the collected fractions was developed. Next, an online-storage recycling CCC mode was designed to enable the active fractions to be stored in coils, and these active fractions were further separated to obtain pure compounds by using sequential recycling elution. In this strategy, active fractions are first identified, and then pure LSD1 inhibitors are isolated in the 2D CCC mode through continuous separation on a single instrument. By using our bioactivity-guided cut CCC strategy, we successfully isolated six natural LSD1 inhibitors from S. baicalensis Georgi, five of which were identified for the first time as natural LSD1 inhibitors.

Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells.

Multidrug resistance (MDR) is one of the major obstacles in cancer chemotherapy. Our previous study has shown that icariin could reverse MDR in MG-63 doxorubicin-resistant (MG-63/DOX) cells. It is reported that icariin is usually metabolized to icariside II and icaritin. Herein, we investigated the effects of icariin, icariside II, and icaritin (ICT) on reversing MDR in MG-63/DOX cells. Among these compounds, ICT exhibited strongest effect and showed no obvious cytotoxicity effect on both MG-63 and MG-63/DOX cells ranging from 1 to 10 µmol·L-1. Furthermore, ICT increased accumulation of rhodamine 123 and 6-carboxyfluorescein diacetate and enhanced DOX-induced apoptosis in MG-63/DOX cells in a dose-dependent manner. Further studies demonstrated that ICT decreased the mRNA and protein levels of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1). We also verified that blockade of STAT3 phosphorylation was involved in the reversal effect of multidrug resistance in MG-63/DOX cells. Taken together, these results indicated that ICT may be a potential candidate in chemotherapy for osteosarcoma.

Targeted dual-mode imaging and phototherapy of tumors using ICG-loaded multifunctional MWCNTs as a versatile platform.

We present the development of indocyanine green (ICG)-loaded and folic acid (FA)-modified multiwalled carbon nanotubes (MWCNTs) as a versatile nanoplatform for targeted dual-mode fluorescence (FL)/photoacoustic (PA) imaging, and photothermal therapy (PTT)/photodynamic therapy (PDT) of tumors in vivo. In this study, acid-treated MWCNTs with carboxyl residues were first covalently conjugated with polyethyleneimine (PEI). This was followed by sequential modification of FA via a polyethylene glycol (PEG) segment, fluorescein isothiocyanate (FITC), and succinic anhydride (SAH), multifunctional FA-modified MWCNTs (MWCNT-PEI·SAH-FITC-PEG-FA) were formed. The functional MWCNTs possess exceptional colloidal stability, good hemocompatibility/cytocompatibility in a studied concentration range, and targeting specificity to FA receptor-overexpressing cancerous cells. Viaπ-π stacking interactions, the MWCNTs enable highly efficient loading of ICG and the ICG-loaded MWCNTs exhibit excellent photostability and can be used for FL imaging/PDT of tumors due to the singlet oxygen (1O2) generation from ICG. In addition, the near-infrared absorption characteristic of ICG also renders the MWCNT nanoplatform with a capacity for simultaneous PA imaging and PTT of tumors. Our study reports a novel theranostic nanosystem that can be used for targeted dual-mode FL/PA imaging and PTT/PDT of tumors in vivo, which may show profound promise for translation into clinical uses.

Multifunctional Fe3O4 @ Au core/shell nanostars: a unique platform for multimode imaging and photothermal therapy of tumors.

We herein report the development of multifunctional folic acid (FA)-targeted Fe3O4 @ Au nanostars (NSs) for targeted multi-mode magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging and photothermal therapy (PTT) of tumors. In this present work, citric acid-stabilized Fe3O4/Ag composite nanoparticles prepared by a mild reduction route were utilized as seeds and exposed to the Au growth solution to induce the formation of Fe3O4 @ Au core/shell NSs. Followed by successive decoration of thiolated polyethyleneimine (PEI-SH), FA via a polyethylene glycol spacer, and acetylation of the residual PEI amines, multifunctional Fe3O4 @ Au NSs were formed. The designed multifunctional NSs possess excellent colloidal stability, good cytocompatibility in a given concentration range, and specific recognition to cancer cells overexpressing FA receptors. Due to co-existence of Fe3O4 core and star-shaped Au shell, the NSs can be used for MR and CT imaging of tumors, respectively. Likewise, the near infrared plasmonic absorption feature also enables the NSs to be used for PA imaging and PTT of tumors. Our study clearly demonstrates a unique theranostic nanoplatform that can be used for high performance multi-mode imaging-guided PTT of tumors, which may be extendable for theranostics of different diseases in translational medicine.

A new picfeltarraenone glycoside from Picria fel-terrae.

AIM: To investigate the chemical constituents from Picria fel-terrae Lour. METHODS: Column chromatography techniques were used to isolate the chemical constituents, physico-chemical constants and spectroscopic analysis were employed for structural elucidation. Results Two triterpenoids named picfeltarraenone I (1) and picfeltarraenin XI (2) were isolated, and their structures were established to be 3,11,22-trioxo-16alpha-hydroxy-(20S,24)-epoxy-cucurbit-5,23-diene (1) and 3,11,22-trioxo-16alpha-hydroxy-(20S,24)-epoxy-cucurbit-5, 23-diene-2beta-O-beta-D-glucopyranoside (2), respectively. CONCLUSION: Compound 2 is a new compound, the 13CNMR data of compound 1 is reported for the first