Current Pharmaceutical Design - Volume 31, Issue 11, 2025

Atherosclerosis refers to the thickening and hardening of artery walls. In our latest experiment, we utilized environmentally friendly techniques to produce multifunctional iron oxide nanoparticles (FeONPs) aimed at reducing inflammation in rats with atherosclerosis.

The formulation was synthesized using curcumin (as the potent bioactive molecule) and was characterized. We assessed the in vitro antioxidant capability of the formulation against DPPH free radicals. Additionally, we quantified the mRNA levels of eNOS, PI3K, and Akt using Real Time-Polymerase Chain Reaction (RT-PCR). We tested the therapeutic impact of the bioactive formulation on a Triton X-100-induced atherosclerosis mouse model.

The crystallinity and magnetic behavior confirmed the magnetic properties of the FeONPs. The DPPH assay exhibited the dose-dependent radical scavenging characteristics of FeONPs. In the animal experiments, significant upregulation of the studied genes was noticed in treated groups 2 and 3 compared to treated group 1. Moreover, the expression of PI3K/eNOS/Akt was greater in treated group 3 than in treated group 2. These results indicate a dose-dependent elevation in target gene expression.

Nevertheless, the variation in gene expression between the negative control and the untreated control was not statistically significant (p > 0.05) across all genes.

The COVID-19 pandemic represents a significant challenge across scientific, medical, and societal dimensions. The unpredictability of the disease progression, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgent need for identifying compounds that target multiple aspects of the virus to ensure swift and effective treatment. Nyctanthes arbortristis L., a delicate, perennial, deciduous shrub found across various Asian regions, has been recognized for its wide range of pharmacological benefits, including hepatoprotective, antimalarial, antibacterial, anti-inflammatory, antioxidant, and antiviral properties.

Various in vitro studies revealed the therapeutic significance of Nyctanthes arbortristis against COVID-19. However, the exact molecular mechanism remains unclarified. In the present study, a network pharmacology approach was employed to uncover the active ingredients, their potential targets, and signaling pathways in Nyctanthes arbortristis for the treatment of COVID-19. In the framework of this study, we explored the active ingredient–target–pathway network and figured out that naringetol, ursolic acid, beta-sitosterol, and daucosterol decisively contributed to the development of COVID-19 by affecting IL6, MAPK3, and MDM2 genes.

The results of molecular docking analysis indicated that Nyctanthes arbortristis exerted effective binding capacity in COVID-19. Further, we disclosed the targets, biological functions, and signaling pathways of Nyctanthes arbortristis in COVID-19. The analysis indicated that Nyctanthes arbortristis could help treat COVID-19 through the enhancement of immunologic functions, inhibition of inflammatory reactions and regulation of the cellular microenvironment. In short, the current study used a series of network pharmacology-based and computational analyses to understand and characterize the binding capacity, biological functions, pharmacological targets and therapeutic mechanisms of Nyctanthes arbortristis in COVID-19.

However, the findings were not validated in actual COVID-19 patients, so further investigation is needed to confirm the potential use of Nyctanthes arbortristis for treating COVID-19.

Cocrystals are an efficient way for the delivery of low soluble drugs but when dissolved they rapidly disproportionate. To formulate the cocrystals in tablets, cocrystals must be stabilized. In this study ibuprofen-nicotinamide (IBU-NIC) cocrystals were synthesized initially by slow solvent evaporation and for bulk production by fast solvent evaporation techniques.

The cocrystals were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectrophotometer (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and optical microscopy. The ibuprofen cocrystals showed greater solubility compared to the parent drug.

Intrinsic dissolution data was utilized for efficacious screening of tablet formulations. Using hydrophilic polymers at a ratio of 6:1 (polymer to IBU-NIC cocrystal ratio), hydroxypropyl methylcellulose (F1), polyvinylpyrrolidone (PVP) K-30 (F2) and PVP K-90 (F3), three tablet formulations were prepared that stabilized cocrystals during dissolution. The drug release profiles after 60 minutes from formulations F1 (92.30), F2 (98.54), F3 (99.88) were all higher compared to the marketed brand BRUFEN^® F0, (79.61%) in a simulated intestinal media (p<0.001).

Significant increase in the dissolution rate of cocrystal was observed with no phase change in all formulations.

Non-small cell lung cancer (NSCLC) represents the leading cause of cancer deaths in the world. We previously found that daidzein, one of the key bioactivators in soy isoflavone, can inhibit NSCLC cell proliferation and migration, while the molecular mechanisms of daidzein in NSCLC remain unclear.

We developed an NSCLC nude mouse model using H1299 cells and treated the mice with daidzein (30 mg/kg/day). Mass spectrometry analysis of tumor tissues from daidzein-treated mice identified 601 differentially expressed proteins (DEPs) compared to the vehicle-treated group. Gene enrichment analysis revealed that these DEPs were primarily associated with immune regulatory functions, including B cell receptor and chemokine pathways, as well as natural killer cell-mediated cytotoxicity. Notably, the NOD-like receptor signaling pathway, which is closely linked to pyroptosis, was significantly enriched.

Further analysis of key pyroptosis-related molecules, such as ASC, CASP1, GSDMD, and IL-1β, revealed differential expression in NSCLC versus normal tissues. High levels of ASC and CASP1 were associated with a favorable prognosis in NSCLC, suggesting that they may be critical effectors of daidzein's action. In NSCLC-bearing mice treated with daidzein, RT-qPCR and Western blot analyses showed elevated mRNA and protein levels of ASC, CASP1, and IL-1β but not GSDMD, which was consistent with the proteomic data.

In summary, this study demonstrated that daidzein inhibits NSCLC growth by inducing pyroptosis. Key pathway modulators ASC, CASP1, and IL-1β were identified as primary targets of daidzein. These findings offer insights into the molecular mechanisms underlying the anti-NSCLC effects of daidzein and could offer dietary recommendations for managing NSCLC.