BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by oxidative stress and impaired skin barrier function. These pathological features contribute to persistent inflammation and symptom exacerbation, highlighting the need for therapies that can both reduce oxidative stress and modulate inflammatory pathways. METHODS:Ulmus pumila Linné (Ulmi) was prepared via hot water extraction and tested for cytotoxicity, antioxidant activity, and anti-inflammatory effects in HaCaT keratinocytes stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). In vivo efficacy was assessed using a 2,4-dinitrochlorobenzene (DNCB)-induced AD model in SKH-1 hairless mice. Bioactive compounds were identified using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS), and molecular docking analysis was performed to evaluate the binding affinity of these compounds to aldehyde dehydrogenase 2 (ALDH2). RESULTS:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays confirmed that Ulmi was safe at concentrations up to 400 μg/mL. In TNF-α/IFN-γ-stimulated HaCaT cells, Ulmi significantly upregulated ALDH2 expression in a dose-dependent manner and reduced reactive oxygen species (ROS) production. The extract also suppressed pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), while inhibiting the activation of nuclear factor kappa B (NF-κB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. In the AD mouse model, Ulmi treatment improved clinical skin scores, reduced epidermal thickness, and decreased inflammatory markers compared to untreated controls. LC-QTOF-MS/MS analysis identified eight bioactive compounds, with procyanidin B2, catechin, and epicatechin as major constituents. Molecular docking revealed that procyanidin B2 had the strongest binding affinity to ALDH2 (-9.5 kcal/mol). CONCLUSIONS:These findings demonstrate that Ulmi effectively ameliorates AD-like symptoms through ALDH2-mediated antioxidant mechanisms and anti-inflammatory effects. The results suggest that Ulmi may serve as a promising natural therapeutic agent for the management of atopic dermatitis.
Aminochrome, an endogenous neurotoxin, has been implicated in the loss of neuromelanin-containing dopaminergic neurons in the nigrostriatal system in Parkinson's disease. Although aminochrome-induced oxidative stress and its inhibitory effects on microtubule polymerization are well documented, its impact on protein aggregation remains poorly understood. The aim of this research was to evaluate the effects of aminochrome on protein aggregate accumulation in SH-SY5Y cells differentiated into dopaminergic neurons. While the role of aminochrome in autophagy has been described, its direct effect on autophagosome-lysosome fusion has not been studied. Our findings reveal that aminochrome, like vinblastine, delays autophagosome-lysosome fusion and induces cell death. This inhibitory effect was also observed in the presence of autophagy inducers, which partially attenuated aminochrome-induced cell death. Under these conditions of disruptions in autophagosome-lysosome fusion, a marked accumulation of perinuclear vimentin and ubiquitin aggregates was observed. Aminochrome also increased colocalization between vimentin and ubiquitin. Interestingly, ubiquitin aggregates were also detected within the nucleus. These findings suggest that aminochrome-induced disruption of the microtubule network, particularly its impairment of autophagosome-lysosome fusion and promotion of protein aggregation, may represent a critical mechanism leading to cell death. In addition, inhibition of autophagosome-lysosome fusion may contribute to the accumulation of perinuclear and nuclear protein aggregates, which may be associated with either toxic or non-toxic pathways. Our findings underscore the therapeutic potential of targeting both microtubule stabilization and proteostasis pathways, including autophagy and the ubiquitin-proteasome system (UPS), in Parkinson's disease, highlighting the need for further research into nuclear proteotoxicity mechanisms.
Scorpion venom peptides, with their stable disulfide backbone, compact structural framework, and highly selective regulation of ion channels, have long been regarded as important molecular probes in neuropharmacology. However, recent studies have revealed their potential for regulating oxidative stress, inflammation, and neuroprotection, making them a new research frontier. In this article, we focus on scorpion venom peptides as drugs, constructing an integrated knowledge framework from structural classification to clinical translation. First, scorpion venom peptides are systematically classified based on cysteine arrangement patterns and three-dimensional folding topology, and their structure-activity relationships are summarized. Based on this, the molecular mechanisms by which scorpion venom peptides regulate ion channels are systematically analyzed. We review the emerging pharmacological activities of scorpion venom peptides. Of particular note, the representative molecule SVHRSP has shown multi-target synergistic antioxidant and neuroprotective activity in models of Parkinson's disease. We also systematically evaluate the application of engineering strategies, including cyclisation modification, nanodelivery, recombinant expression, and AI-assisted optimization, to overcome the translational bottlenecks in the development of scorpion venom peptides. However, it should be noted that most SVHRSP-related findings have been reported by a single research group; independent replication, pharmacokinetic characterization, and human efficacy data are still lacking. Its IND approval permits clinical investigation but does not yet constitute proven therapeutic benefit in patients. By integrating molecular structure, redox regulation mechanisms, and translational medicine perspectives, this review aims at providing a theoretical basis and practical pathways for scorpion venom peptides as precision therapeutic molecules for oxidative stress-related diseases.
Optimizing the extraction of bioactive compounds from Solidago sp. is essential for the development of plant-derived products with therapeutic and nutraceutical potential. Microwave-assisted (MW) and thermal maceration (TM) extraction of S. canadensis aerial parts were comparatively investigated to maximize total flavonoid content (TFC). The obtained extracts were subsequently freeze-dried for storage prior to chemical and biological analyses. Extraction conditions were optimized using a Box-Behnken design. Chemical characterization was performed by FTIR, HPLC-PDA, LC-MS/MS, and GC-MS, enabling detailed profiling of phenolic compounds and terpenoids. Antioxidant capacity was assessed using the DPPH radical scavenging assay, while cytotoxic activity was evaluated against HepG2, HCT-8, and HT-29 tumor cell lines, with HEK-293 cells used as a non-tumorigenic control cell line. Multivariate analysis (PCA) was applied to establish relationships between phytochemical composition and biological responses. Higher TFC values were obtained using MW extraction, whereas TM extracts exhibited greater antioxidant activity. Both extract types induced selective cytotoxic effects against tumor cell lines, while maintaining negligible toxicity toward normal HEK-293 cells. PCA revealed distinct clustering patterns between MW and TM extracts and confirmed a strong association between phenolic composition and bioactivity. The combination of optimized extraction, freeze-drying, and integrated chemical-biological evaluation produced S. canadensis extracts with well-defined phytochemical profiles and biological activity, supporting their potential use in nutraceutical, and pharmaceutical applications.
