In vitro testing is increasingly replacing systemic pharmacokinetic studies in assessing the equivalence of generic and reference locally acting nasal sprays. Establishing reliable in vitro methods and investigating factors that may affect equivalence tests is crucial. In this study, we evaluated the in vitro atomization characteristics of a self-prepared budesonide nasal spray (Formulation A) and a reference drug (Formulation B). A simple and efficient Python program was used to assess population bioequivalence, achieving a high level of automation with audit trail capabilities. The single actuation content, droplet size distribution, and plume geometry met the criteria for population bioequivalence (Hη <0). As the actuation force increased, droplet size decreased, with D90 (the diameter at a cumulative volume of 90%, the same below) exhibiting greater sensitivity to changes than D10 and D50. The spray patterns of the two formulations differed significantly, with Formulation B exhibiting a significant larger spray area than Formulation A. Stroke velocity was the factor with the largest influence on the spray pattern. For both formulations, drug particles <8.6 μm were below the HPLC detection limit (1.016 ng), confirming the safety of the formulation. The results indicate that device and drug interactions significantly influence nasal spray quality assessments, providing guidance for future formulation development and quality evaluation.

Diabetic encephalopathy (DE) is a major complication of diabetes and there is a need of development of new therapy for the management of it. Present investigation evaluates the effect of vanillin against diabetic encephalopathy in rat model. Diabetic encephalopathy was induced by the admiration of 30 % fructose for 4 week and later streptozotocin (STZ, 35 mg/kg, i.p.) was given to induce DE after 6 weeks of its administration. All the rats were treated with vanillin 100 and 200 mg/kg, p.o. for the duration of 6 week. Behavioural changes like cognitive and motor function were determined in vanillin treated DE rats. Parameters of oxidative stress and cytokines were estimated in the brain tissue of vanillin treated DE rats. Relative mRNA expression of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3), Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) were determined by Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) and histopathological changes of brain tissue was performed using H&E staining. Cognitive and motor functions were reversed in vanillin treated DE rats. Treatment with vanillin attenuates the altered parameters of oxidative stress and cytokines in the brain tissue of DE rats. There was significant reduction in the mRNA expression of NLRP3 and increase in mRNA expression of Nrf2 and HO-1 in vanillin treated group than DE group of rats. In conclusion, data of the study shows neuroprotective of vanillin against DE in rat by regulating NLRP3 signalling.

Asthma is a chronic respiratory disease characterized by inflammation, airway remodeling, and fibrosis, which are critical aspects in its pathogenesis. TGF-β is a key regulator of these processes, promoting collagen deposition and fibrotic remodeling in the lungs and heart. Decorin (Dcn), an extracellular matrix proteoglycan, binds to TGF-β and regulates its bioavailability, potentially offering a therapeutic strategy for controlling remodeling in asthma. We evaluated anti-remodeling activity of Dcn on allergic asthma pathogenesis in mice. Allergic asthma mouse was treated with Dcn. Then eosinophil in lung fluid, levels of IgE, IL-4, IL-5, IL-13, leukotrienes, hydroxyproline, and TGF-β were measured. Lung histopathology was performed to assess metaplasia of goblet cell, mucus production, and eosinophilic inflammation. Treatment by Dcn could significantly (P<0.05) control eosinophils, levels of IgE, IL-4, IL-13, leukotriene, remodeling factors, hyperplasia of the goblet cell, mucus hyper-production, inflammation of the perivascular and peribronchial area. Dcn effectively reduces key inflammatory and fibrotic markers associated with allergic asthma. By modulating TGF-β signaling, Dcn could be a promising therapeutic strategy for controlling asthma pathophysiology, particularly in preventing lung remodeling and related cardiovascular complications.

Coumarins are naturally occurring polyphenolic compounds with reported antioxidant and neuroprotective properties. In this study, we evaluated five coumarin derivatives—umbelliferone, coumarin, xanthotoxin, esculetin, and scopoletin—using human SH-SY5Y neuroblastoma cells as an in vitro model of neuronal injury. Cytotoxicity was assessed to determine safe concentration ranges, followed by testing for protection against glutamate-induced excitotoxicity. Esculetin and scopoletin significantly increased cell viability (p < 0.05), while the other compounds showed no effect. These findings suggest that specific structural features, such as hydroxyl and methoxy substitutions, are important for neuroprotective activity. Esculetin and scopoletin emerge as promising candidates for further investigation in models of neurodegenerative disease.

Background: Esophageal cancer (EC) maintains a visible disease burden in China, constituting a major public health challenge among gastrointestinal malignancies, with limitations in the efficacy of existing single-treatment modalities. Andrographolide, a natural active component, has yet to have its radiosensitizing mechanisms fully elucidated. Objectives: This article was designed to elucidate Andrographolide’s synergistic inhibition with radiotherapy and its molecular basis on human esophageal squamous cell carcinoma (EC9706) cells. Methods: Using EC9706, cell proliferation was detected by the CCK-8 assay (at 24/48/72 h), migration ability was assessed by the scratch assay (at 12/24/48 h), radiosensitivity was analyzed by the colony formation (CF) assay (at 0-6 Gy), and the level of associated proteins was subjected to detection by Western blot (WB). Results: The combination group (DG) suggested the strongest proliferation inhibition at all time points [vs. control group (AG)], with the most visible distinction at 72 h. The scratch healing rate was the lowest (at 48 h vs. AG) (P < 0.01). As the radiation dose increased, the CF rate (CFR) declined markedly (6 Gy vs. AG, P < 0.001). Molecular detection revealed that the DG had the highest expression of Cleaved Caspase-3 and Bax, and the lowest expression of Bcl-2, NF-κB p65, and p-IκBα (P < 0.01). Conclusion: Andrographolide enhances the radiosensitivity of EC cells by activating apoptosis pathways and inhibiting the NF-κB signaling pathway, providing experimental evidence for clinical combined treatment.

The purpose of this work aimed to determine different topological indices based on adjacency and distance matrix for selected antimicrobial, antiviral and immunosuppressive drug substances. The following topological indices: Gutman (M, Mν), Randić (0χ, 1χ, 0χν, 1χν), Wiener (W), Rouvray-Crafford (R) and Pyka (A, 0B, 1B) were calculated for the studied compounds. Furthermore, these indices were related with various physicochemical properties of these compounds including those key in the ADME process (absorption, distribution, metabolism, and excretion), such as lipophilicity parameters obtained using both theoretical (logP values) and experimental (RMW values from thin-layer chromatography) methods. The quantitative structure–property relationship (QSPR) analysis of presented topological indices shows a good correlation of studied descriptors with certain physicochemical properties of examined drugs. The obtained linear regression models can be helpful to predict these physicochemical properties of new derivatives of tested compounds and thus are significant in pharmaceutical product design. This study confirms that the newly calculated descriptors (TIs) represent an innovative tool in drug analysis and at the same time TIs are useful in determining important parameters for ADME profile prediction.

Herbal have gained recognition as valuable adjuncts in managing cardiovascular disease (CVD), offering multi-targeted benefits across key risk factors. This review summarizes data from different data bases over the past decade, focusing on herbs with traditional and emerging cardiovascular applications. The selection is supported by the European Medicines Agency (EMA) and its Committee on Herbal Medicinal Products (HMPC) monographs. Key herbs include artichoke (Cynara cardunculus L. syn. Cynara scolymus L.) turmeric (Curcuma longa L.), Citrus bergamia (Citrus bergamia Risso & Poit.), garlic (Allium sativum L.), ginkgo (Ginkgo biloba L.), danshen (Salvia miltiorrhiza Bunge), hawthorn (Crataegus spp.), Terminalia arjuna (Terminalia arjuna (Roxb. ex DC.) Wight & Arn.), Asian ginseng (Panax ginseng C.A.Meyer.), green tea (Camellia sinensis (L.) Kuntze), ginger (Zingiber officinale Roscoe), black cumin (Nigella sativa L.), motherwort (Leonurus cardiaca L), and others. These plants are rich in bioactive compounds such as flavonoids, polyphenols, and organosulfur compounds, which exert antioxidant, anti-inflammatory, antihypertensive, and lipid-lowering effects. Clinical evidence supports garlic’s impact on blood pressure and lipids, hawthorn’s benefits in heart failure, and ginseng and ginkgo’s role in vascular function. Curcumin and gingerols contribute to anti-inflammatory activity and improved metabolic profiles. Additional herbs like bergamot and hibiscus also show cholesterol- and blood pressure-lowering effects. While the overall safety profile is favourable, herb–drug interactions must be considered. Collectively, these herbal agents offer a natural, accessible, and cost-effective complement to conventional CVD therapies. However, further large-scale clinical trials are essential to confirm efficacy, establish standardized dosing, and evaluate long-term safety in cardiovascular care.

The search for new compounds with antibacterial activity is of critical importance in modern medicine. The rise of antibiotic-resistant bacteria poses a serious global health threat, making it increasingly difficult to treat common infections. Discovering novel antibacterial agents can help combat these resistant strains and ensure effective treatment options remain available. In this study, eighteen novel fluorobenzhydrazide derivatives, including linear thiosemicarbazides and cyclic 1,2,4-triazoles, were synthesized and evaluated for their in vitro antibacterial activity against various bacterial strains. Among the synthesized compounds, thiosemicarbazide 6, which contains a diethylaminophenyl substituent, exhibited moderate antibacterial activity, particularly against Gram-positive bacteria. This thiosemicarbazide successfully inhibited the growth of all Staphyloccocus aureus strains with an MIC of 64 µg/mL. To explore the potential antibacterial mechanism, molecular docking and molecular dynamics simulations were performed to assess the interaction of these compounds with Ddl ligase and DNA gyrase. Notably, 4-(4-N,N-diethylaminophenyl)-1-(3-fluorobenzoyl)thiosemicarbazide demonstrated a binding mode comparable to that of a known inhibitor, highlighting its potential as a lead compound and suggesting possible directions for further structural modifications.

Endoplasmic reticulum stress (ERS) is an important link leading to the occurrence of insulin resistance (IR). The study aimed to investigate the role of Chinese medicine Dihydromyricetin (DHM) in IR in HepG2 cells and type 2 diabetes mellitus (T2DM) rats and its possible mechanism under the participation of ERS. HepG2 cells were treated with 5×10−6 mol/L insulin to establish an IR cell model. T2DM rats were established through the combination of low-dose streptozocin (STZ) and a high-fat diet. T2DM rats were given low doses (DHM-L) or high doses (DHM-H) of DHM. OGTT was performed for the glucose tolerance evaluation. Western blot was done for the protein detection. DHM improved the insulin sensitivity, lipid levels, and inflammatory response in HepG2 cells induced by IR. DHM decreased the body weight, FBG, FINS, and HOMA-IR of T2DM rats. OGTT test demonstrated the increase of blood glucose and area under the curve (AUC) in T2DM rats, which was reduced by DHM treatment in a dosed manner. The increased TC, TG, LDL, and reduced HDL in T2DM rats were reversed by DHM, which is related to the improvement of lipid metabolism. For mechanism, DHM inhibited the ERS signaling and inflammatory response. DHM attenuates IR and lipid metabolism in a dose-dependent manner in T2DM rats, and the mechanism might be related to improving liver ERS and inhibiting inflammation.