Methicillin-resistant Staphylococcus aureus (MRSA) is a serious and rapidly growing threat to human beings. Emodin has a potent activity against MRSA; however, its usage is limited due to high hydrophobicity and low oral bioavailability. Thus, the coaxial electrospinning nanofibers encapsulating emodin in the core of hydrophilic poly (vinylpyrrolidone), with a hygroscopic cellulose acetate sheath, have been fabricated to provide long-term effect against MRSA. Scanning electron microscopy and transmission electron microscopy confirmed the nanofibers had a linear morphology with nanometer in diameter, smooth surface, and core-shell structure. Attenuated total reflection-Fourier transform infrared spectra, X-ray diffraction patterns, and differential scanning calorimetric analyses verified emodin existed in amorphous form in the nanofibers. The nanofibers have 99.38 ± 1.00% entrapment efficiency of emodin and 167.8 ± 0.20% swelling ratio. Emodin released from nanofibers showed a biphasic drug release profile with an initial rapid release followed by a slower sustained release. CCK-8 assays confirmed the nontoxic nature of the emodin-loaded nanofibers to HaCaT cells. The anti-MRSA activity of the nanofibers can persist up to 9 days in AATCC147 and soft-agar overlay assays. These findings suggest that the emodin-loaded electrospun nanofibers with core-shell structure could be used as topical drug delivery system for wound infected by MRSA.

Morphine dependence, a devastating neuropsychiatric condition, may be closely associated with gut microbiota dysbiosis. Ginsenoside Rg1 (Rg1), an active ingredient extracted from the roots of Panax ginseng C.A. Meyer, has potential health-promoting effects on the nervous system. However, its role in substance use disorders remains unclear. Here, we explored the potential modulatory roles of Rg1 in protection against morphine dependence. Conditioned place preference (CPP) was used for establishing a murine model of morphine dependence. 16S rRNA gene sequencing and metabolomics were performed for microbial and metabolite analysis. Molecular analysis was tested for evaluating the host serum and brain responses. Rg1 prevented morphine-induced CPP in mice. The 16S rRNA gene-based microbiota analysis demonstrated that Rg1 ameliorated morphine-induced gut microbiota dysbiosis, specifically for Bacteroidetes. Moreover, Rg1 also inhibited gut microbiota-derived tryptophan metabolism and reduced the serotonin, 5-hydroxytryptamine receptor 1B (5-HTR1B), and 5-hydroxytryptamine receptor 2 A (5-HTR2A) levels. However, the Rg1-induced amelioration of CPP was not observed in mice when their gut microbiome was depleted by non-absorbable antibiotics. Subsequently, gavage with Bacteroides vulgatus increased the abundance of Bacteroidetes. B. vulgatus supplementation synergistically enhanced Rg1-alleviated morphine-induced CPP in mice with microbiome knockdown. Co-treatment with B. vulgatus and Rg1 produced suppressive effects against morphine dependency by inhibiting tryptophan metabolism and reducing the serotonin and 5-HTR1B/5-HTR2A levels. The gut microbiota-tryptophan metabolism-serotonin plays an important role in gut-brain signaling in morphine disorders, which may represent a novel approach for drug dependence treatment via manipulation of the gut microbial composition and tryptophan metabolite.

Methamphetamine (Meth) is a highly addictive substance and the largest drug threat across the globe. There is evidence to indicate that Meth use has serious damage on central nervous system (CNS) and heart in several animal and human studies. However, the connection in the process of Meth addiction between these two systems has not been determined. Emerging data suggest that extracellular vesicles (EVs) carrying behavior-altering microRNA (miRNAs) play a crucial role in cell communication between CNS and peripheral system. Rhynchophylline (Rhy), an antiaddictive alkaloid, was used to protect the brain and heart from Meth-induced damage, which has caught our attention. Here, we used Meth-dependent conditioned place preference (CPP) animal model and cell model to verify the protective effect of Rhy-treated EVs. Further, small RNA sequencing analysis, qPCR, dual-luciferase reporter assay, and transfection test were used to identify the key EVs-encapsulated miRNAs, isolated from cultured H9c2 cells with different treatments, involved in the therapeutic effect and the underlying mechanisms of Rhy. The results demonstrate that Rhy-treated EVs exert protective effects against Meth dependence through the pathway of miR-183-5p-neuregulin-1 (NRG1). Our collective findings provide novel insights into the roles of EVs miRNAs in Meth addiction and support their potential application in the development of novel therapeutic approaches.

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and ginger contains phenolic constituents with anti-inflammatory potential. This study evaluated the antiarthritic efficacy of ginger ethanolic extract (GE) and explored its potential mechanisms through integrated pharmacological and computational approaches. Methods: GE was prepared by 70% ethanol reflux extraction and administered to adjuvant-induced arthritis (AIA) rats, with methotrexate as a positive control. Body weight; paw swelling; arthritis index; spleen index; and serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured. Chemical profiling was performed by ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS), followed by network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Results: GE attenuated paw edema, arthritis index elevation, splenic enlargement, and elevated serum inflammatory mediators in AIA rats. UPLC-Q-TOF-MS/MS annotated 38 constituents, mainly gingerols, shogaols, gingerdiones, gingerdiols, and related phenolic derivatives. Network analysis identified 217 overlapping ginger- and RA-associated targets, with TNF, IL6, and matrix metalloproteinase 9 (MMP9) prioritized among inflammatory and matrix-remodeling nodes. Docking and MD simulations supported stable predicted interactions for 8-gingerol-TNF and 6-gingerol-MMP9. Conclusions: GE showed antiarthritic activity in AIA rats. The integrated chemical, in vivo, and computational data suggest that ginger phenolics may modulate inflammatory mediators and candidate RA-related pathways; however, these mechanisms remain exploratory and require histological, tissue-level, and molecular validation.