Lonicera rupicola Hook.f.et Thoms flavonoids ameliorated dysregulated inflammatory responses, intestinal barrier, and gut microbiome in ulcerative colitis via PI3K/AKT pathway.

BACKGROUND: Lonicera rupicola Hook.f.et Thoms (LRH) is used as a customary medicinal herb in Tibetans. And LRH flavonoids have excellent anti-inflammatory and antioxidant pharmacological activities. However, the specific effects of LRH and its mechanism remain unknown, and there is a deficiency of systematic research, leading to the waste of LRH as a medicinal resource. PURPOSE: In this study, in an attempt to rationalize the development and utilization of Tibetan herbal resources, the therapeutic efficacy and the underlying molecular mechanisms of LRH flavonoids on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) were investigated, establishing the favorable basis for the pharmacodynamic material basis of LRH and providing a scientific basis for the discovery of new drugs for the treatment of UC. METHODS: Firstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used for identification and detection of the flavonoid components of LRH. Meanwhile, their potential targets, biological functions and signaling pathways were predicted with the assistance of network pharmacology analysis. Subsequently, pharmacological efficacy of LRH were evaluated by body weight loss, colon length, disease activity index (DAI), histology observation and the expression levels of inflammatory mediators, messenger RNA (mRNA) and tight junction proteins. Moreover, in the present investigation, we also profiled the gut microbiome via high-throughput sequencing of the V3-V4 region of 16S ribosomal DNA (rDNA) for bacterial community composition and diversity by Illumina MiSeq platforms. Finally, the key regulatory proteins in the PI3K/AKT pathways were measured to investigate their underlying molecular mechanisms. RESULTS: A total of 37 LRH flavonoid components were identified and detected by UPLC-MS/MS, and 12 potential active components were obtained after screening. 137 of their common targets with UC were further predicted. GO and KEGG pathway enrichment analysis and molecular docking experiments demonstrated that LRH flavonoids could interfere with UC through "multi-component-multi-target-multi-pathway". In the animal experiments, LRH flavonoids could significantly attenuate UC as demonstrated by reducing the body weight loss and DAI, restoring colon length, decreasing oxidative stress, and improving the intestinal epithelial cell barrier. The mRNA and proteins expression levels of inflammatory mediators were returned to dynamic balance following LRH flavonoids treatment. 16S rDNA sequence analysis indicated that LRH flavonoids promoted the recovery of gut microbiome. And the PI3K/AKT pathway was significantly suppressed by LRH flavonoids. CONCLUSIONS: LRH flavonoids exhibited multifaceted protective effects against DSS-induced UC in mice through mitigating colon inflammation and oxidative stress, restoring epithelial barrier function, and improving the gut microenvironment potentially through modulation of the PI3K/AKT pathway. This finding demonstrated that LRH flavonoids possessed great potential for becoming an excellent drug for the treatment of UC.

Exploration of the Wound Healing Potential of Thermoplastic Polyurethane Electrospun Membrane Incorporated with Phenolic Acids in Spenceria ramalana Trimen.

Wound healing process is usually accompanied by infection and the wound dressing loaded with antibiotics is usually used to treat skin wound. However, the intensive use of antibiotics may lead to development of resistance and the antibiotic resistance has become a major global problem. Finding new wound dressing with sustained antibacterial property to overcome the problem of resistance is one of clinical challenge. In this work, phenolic acids in Spenceria ramalana Trimen and sliver nanoparticle incorporated thermoplastic polyurethane nanofibrous membrane (TPU/AgNPs/TPA) are fabricated via electrospinning. The TPU/AgNPs/TPA membrane exhibits excellent physicochemical properties with uniform morphology, good mechanical capacity, and appropriate hydrophilia providing suitable environment for wound healing. Moreover, the TPU/AgNPs/TPA membrane shows mild antioxidant property and exhibits continuous antibacterial activity against Staphylococcus aureus and Escherichia coli especially against drug-resistant E. coli. The antibacterial efficiency is as high as 99% lasting for 36 h. Furthermore, the TPU/AgNPs/TPA membrane used as wound dressing can accelerate wound healing through downregulating TNF-α and IL-1ß and upregulating vascular endothelial growth factor and epidermal growth factor. Therefore, the TPU/AgNPs/TPA membrane presented in this work with good antibacterial activity is an excellent wound dressing and has great potential in wound healing applications to overcome the problem of resistance.

Cyclodextrin metal-organic framework as vaccine adjuvants enhances immune responses.

It is urgently needed to develop novel adjuvants for improving the safety and efficacy of vaccines. Metal-organic frameworks (MOFs), with high surface area, play an important role in drug delivery. With perfect biocompatibility and green preparation process, the γ-cyclodextrin metal-organic framework (γ-CD-MOF) fabricated with cyclodextrin and potassium suitable for antigen delivery. In this study, we modified γ-CD-MOF with span-85 to fabricate the SP-γ-CD-MOF as animal vaccine adjuvants. The ovalbumin (OVA) as the model antigen was encapsulated into particles to investigate the immune response. SP-γ-CD-MOF displayed excellent biocompatibility in vitro and in vivo. After immunization, SP-γ-CD-MOF loaded with OVA could induce high antigen-specific IgG titers and cytokine secretion. Meanwhile, SP-γ-CD-MOF also significantly improved the proliferation of spleen cells and activated and matured the bone marrow dendritic cells (BMDCs). The study showed the potential of SP-γ-CD-MOF in vaccine adjuvants and provided a novel idea for the development of vaccine adjuvants.

Electrospun Fibrous Membrane Containing a Cyclodextrin Covalent Organic Framework with Antibacterial Properties for Accelerating Wound Healing.

Skin wounds are usually accompanied by bacterial infections and inflammations, leading to delayed wound healing, which remain a great challenge in clinical treatment. Therefore, it is of great significance to develop wound dressings that inhibit bacterial infections to accelerate wound healing. Herein, we reported the fabrication of inclusion complex (a ß-cyclodextrin covalent organic framework loaded with enrofloxacin and flunixin meglumine)-incorporated electrospun thermoplastic polyurethane fibers (named ENR-FM-COF-TPU) via electrospinning. The obtained ENR-FM-COF-TPU fibrous membrane exhibited excellent physicochemical and biological properties such as uniform and stable morphology, proper hydrophobicity, good water uptake capacity, and admirable biocompatibility, which showed perfect behavior as a wound dressing. In addition, the ENR-FM-COF-TPU membrane achieved a sustained drug release of enrofloxacin and flunixin meglumine and displayed powerful antibacterial activity against Staphylococcus aureus and Escherichia coli with 99% inhibitory efficiency for 50 h. More importantly, the wound healing therapy effect was investigated using a full-thickness skin defect model of mice. It suggested that the ENR-FM-COF-TPU membrane could significantly accelerate and enhance wound healing through downregulating inflammatory cytokines (IL-1ß and TNF-α) and increasing the expression of growth factors (VEGF and EGF). Due to its excellent properties, the ENR-FM-COF-TPU membrane may have promising potential in wound healing applications.

Enrofloxacin/florfenicol loaded cyclodextrin metal-organic-framework for drug delivery and controlled release.

We presented an antibiotic-loaded γ-cyclodextrin metal-organic framework that delivered antibiotics suitable for the treatment of bacterial infections. The γ-cyclodextrin metal-organic framework was developed using γ-cyclodextrin and potassium ion via the ultrasonic method. The antibiotic (florfenicol and enrofloxacin) was primarily encapsulated into the pore structures of γ-CD-MOF, which allowed the sustained release of antibiotics over an extended period of time in vitro and in vivo. Notably, antibiotics-loaded γ-CD-MOF showed much superior activity against bacteria than free antibiotics (lower MIC value) and displayed better long-lasting activity (longer antibacterial time). The antibiotics-loaded γ-CD-MOF showed nontoxic and perfect biocompatibility to mammalian cells and tissues both in vitro and in vivo. These materials thus represent a novel drug-delivery device suitable for antibiotic therapy. This research is of great significance for reducing the generation of bacterial resistance and providing new ideas for the application of γ-CD-MOF.