Current Pharmaceutical Design - Current Issue

Dysphania ambrosioides, commonly known as “mastruz,” is a medicinal plant traditionally used for its therapeutic properties, including antimicrobial and anti-inflammatory effects. Previous studies have also suggested its antitumor potential. However, its role in oral squamous cell carcinoma (OSCC) remains unexplored. This study aimed to evaluate the in vitro cytotoxic effects of D. ambrosioides extracts on SCC4 (OSCC) and HaCaT (human keratinocyte) cell lines.

Crude extracts were obtained using different methods, including hexanic, ethanolic, hydroethanolic (7:3), and aqueous extractions, all performed ultrasonic-assisted extraction. The extracts were tested at concentrations ranging from 7.81 µg/mL to 1000 µg/mL using 2-fold serial dilutions. Cell viability was assessed after 48 hours of treatment using the MTT assay, with DMSO as the control.

The extracts exhibited concentration-dependent cytotoxic effects on both cell lines, with HaCaT cells showing greater sensitivity. However, the lack of selectivity toward tumor cells over normal cells suggests a broad-spectrum cytotoxic activity without tumor-specific therapeutic targeting.

These findings highlight the need for further fractionation of the extracts and identification of the bioactive compounds responsible for the observed effects. Although the extracts demonstrated significant cytotoxic activity, their therapeutic potential should not be limited to cytotoxicity alone. Future studies should explore additional biological activities, such as anti-inflammatory or immunomodulatory properties, to fully understand the therapeutic applications of D. ambrosioides.

The autoimmune inflammatory disease known as rheumatoid arthritis (RA) has a complicated and poorly understood etiology. Fibroblast-like synoviocytes (FLSs) have tumor-like characteristics in RA, including aggressive growth and heightened activation that leads to the release of pro-inflammatory factors. These processes are essential for the gradual deterioration of joint tissues. Kaempferol, with the chemical formula 3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one, is found in many different types of plants and plant families. The pharmacological effects of this substance have been well-documented. The benefits of this substance encompass protection for the heart and brain, as well as fighting inflammation, bacteria, cancer, osteoporosis, and allergies. It also has properties that can help with anxiety, pain relief, and hormonal balance. However, its precise function in the management of RA is still unclear.

To investigate the effect of kaempferol on apoptosis in RA FLSs and elucidate the underlying mechanisms.

We used the CCK-8 assay to assess the effects of different kaempferol concentrations on RA FLSs. We also used flow cytometry with Annexin V-FITC/PI staining to analyse cell cycle distribution and quantify apoptotic cells. To verify apoptosis, the TUNEL test was employed. Important proteins associated with apoptosis were verified to be expressed using western blotting. Finally, network pharmacology analysis was used to identify potential kaempferol targets, and their interactions with AKT1, PIK3R1, and HSP90AA1 proteins were studied using molecular docking and molecular dynamics simulations.

Kaempferol treatment significantly increased apoptosis in RA FLSs, up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2. Specifically, kaempferol at 100 and 200 μM increased the apoptosis index to 29.77 ± 6.02% and 55.63 ± 11.05%, respectively, compared to the control. The induction of caspase-9 and caspase-3 cleavage was observed, indicating the activation of the mitochondrial pathway. Kaempferol also inhibited the phosphorylation of PI3K and Akt, with a significant reduction in their activation. Molecular docking studies demonstrated that kaempferol interacted with AKT1, PIK3R1, and HSP90AA1 proteins, with binding energies of -6.51, -4.26, and -6.51 kcal/mol, respectively, suggesting a strong affinity and potential direct impact on these proteins.

Kaempferol induces apoptosis in RA FLSs by inhibiting phosphorylation of the PI3K/Akt signaling pathway, increasing levels of pro-apoptotic proteins, and decreasing levels of anti-apoptotic proteins. Thus, kaempferol, a naturally occurring flavonoid, has great promise in the management of RA.

Rheumatoid arthritis (RA) is a chronic inflammatory condition of the joints and a leading cause of global disability. However, the use of current anti-inflammatory treatments is often limited by serious side effects and multi-organ toxicity, necessitating the exploration of safer alternatives.

This study aims to investigate the anti-rheumatic potential of natural compounds of Cassia angustifolia as small-molecule inhibitors of PTGS2.

The therapeutic potential of C. angustifolia was evaluated through antioxidant and anti-inflammatory assays. Gas chromatography-mass spectrometry (GC-MS) was used to identify its constituents. ADMET profiling (absorption, distribution, metabolism, excretion, and toxicity), network pharmacology, and molecular dynamics simulation were employed to uncover the active compounds against PTGS2 for RA treatment.

C. angustifolia extract contained significant phenolic (18.2 ± 0.008 mg GAE/g DW) and flavonoid (27.57 ± 0.03 mg RE/g DW) content. GC-MS yielded 288 compounds of which four passed the toxicity parameters. Protein-protein interaction analysis revealed 10 RA-related targets, with PTGS2 emerging as the most prominent one. Molecular docking and simulations revealed that compound-2 [2-Benzo [1,3] dioxol-5-yl-8-methoxy-3-nitro-2H-chromene] and compound-4 [alpha-hydroxy-N-[2-methoxyphenyl]-benzene propanamide] binds strongly with PTGS2 (-7.7 kcal/mol and -7.9 kcal/mol, respectively) predicting its stable interaction.

C. angustifolia compounds present a significant potential as PTGS2 inhibitors, warranting further in vitro and in vivo investigations to confirm their therapeutic efficacy against RA.

This study aimed to formulate and evaluate dimenhydrinate (DMH) as fast-disintegrating tablets (FDTs) complexed with β-cyclodextrin (β-CD) to enhance its solubility, dissolution profile, and pharmacological performance.

A DMH:β-CD inclusion complex was prepared at a 1:1 molar ratio using the kneading method. Characterization was performed through phase solubility studies, FTIR analysis, molecular docking, and in vitro dissolution testing. FDTs were developed using various superdisintegrants and assessed for quality attributes of a tablet, including hardness, friability, wetting time, water absorption ratio, and drug content.

Phase solubility and FTIR analyses confirmed the formation of a stable DMH:β-CD complex. Molecular docking indicated a binding affinity of -4.2 kcal/mol between β-CD and diphenhydramine. Among the FDT formulations, CP3 containing 9% crospovidone showed the best performance, with a disintegration time of 4.3 seconds and the highest drug release rate. In vivo pharmacological tests demonstrated enhanced sedative and antiemetic activities of the optimized FDTs compared to conventional DMH formulations.

The findings suggest that cyclodextrin-based complexation combined with orodispersible tablet technology can significantly enhance DMH's pharmacological efficacy and patient compliance. However, additional investigations on long-term stability, pharmacokinetics, and clinical scalability are warranted.

The DMH:β-CD FDTs developed in this study offer promising improvements in solubility, dissolution, and therapeutic performance, indicating their potential for better clinical outcomes and patient acceptability.