Future Journal of Pharmaceutical Sciences最新文献

Background

In the current study, various S-naproxen derivatives (NDs) were evaluated for their analgesic and anti-inflammatory activities using in vivo models, along with molecular docking studies. The analgesic potential was assessed through acetic acid-induced writhing, hot plate, and formalin-induced jumping tests. Anti-inflammatory effect was investigated using carrageenan-induced paw edema model. An acute toxicity study was also conducted to ensure safety.

Results

All tested NDs in different doses were found to be safe in the acute toxicity study. In the acetic acid-induced pain model, NDs (5 mg/kg) showed a significant (p < 0.001) analgesic effect with compound 3 and 7 demonstrated maximum effect (80%). In hot plate test, compounds 7, 8, and 9 showed central analgesic activity with percent effects of 61, 48 and 45%, respectively (p < 0.05). In formalin-induced pain model, all NDs demonstrated significant analgesic activity (p < 0.001), with a stronger effect in the second phase of the test. For anti-inflammatory activity, NDs showed variable effects, with compound 7 (81.55%) and compound 8 (80.14%) showing the highest activity in the third hour of the carrageenan-induced paw edema model. Molecular docking studies confirmed strong interactions of NDs with both opioid receptors and COX-II enzymes, supporting their peripheral and central analgesic mechanisms.

Conclusion

The findings suggest that the tested S-naproxen derivatives exhibit significant analgesic and anti-inflammatory activities. The combination of in vivo and in silico data supports the analgesic and anti- inflammatory effects.

Neurodevelopmental disorders (NDDs) significantly affect brain development, leading to challenges in communication, learning, and emotional regulation. This review examines the role of genetic factors, particularly copy number variations (CNVs), and critical structural alterations in the genome that influence gene dosage and biological functions. We focus on key CNV regions, including 16p11.2, 22q11.2, 1q21.1, and 15q11.2, associated with various NDDs and their impact on cognitive and behavioral outcomes. CNVs can disrupt gene function, contributing to genetic instability and dysregulated pathways in NDDs. Acknowledging limitations in current literature, such as sample size and selection bias, we emphasize the need for a larger, more diverse population and longitudinal studies. Additionally, we identify gaps in understanding genetic-environmental interactions and suggest that advanced genomic technologies could enhance research. Understanding how CNVs influence DNA repair mechanisms may lead to potential interventions to mitigate genomic instability in NDDs.

Graphical abstract

Background

Alopecia, a condition characterized by hair loss, affects millions of people worldwide and has a substantial impact on their quality of life. Traditional medicines frequently have limitations and side effects, prompting the development of innovative therapeutic agents.

Objectives

Lupeol (LUP), a natural triterpenoid, has garnered attention for its anti-inflammatory and antioxidant potential, making it a promising candidate for alopecia management. Encapsulation of LUP-rich extracts enhances bioavailability and stability, facilitating their incorporation into dietary supplements.

Methods

The integration of AI-assisted predictive tools in this review has provided deeper insights into the therapeutic potential of LUP for alopecia management.

Results

Our findings indicate that LUP exhibits significant potential in promoting hair growth and reducing inflammation associated with alopecia. The AI-assisted analysis revealed key molecular pathways through which LUP exerts its effects, including the modulation of EGFR, PTGS2, ESR1, and AR targets and inhibition of pro-inflammatory mediators (COX-2). Additionally, predictive models suggest favorable pharmacokinetics and minimal adverse effects, supporting the feasibility of LUP as a therapeutic agent. Our findings advocate for further preclinical and clinical studies to validate these results and explore the full scope of LUP’s benefits.

Conclusion

This approach exemplifies the synergy between traditional pharmacological research and cutting-edge AI technology, paving the way for innovative treatments in dermatology.

Objectives

This investigation aims to assess the prognostic significance of the pre-therapeutic prognostic nutritional index (PNI) in individuals with hepatocellular carcinoma (HCC) undergoing treatment with either sorafenib or regorafenib.

Methods

A retrospective cohort study was conducted on 150 patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC treated with sorafenib (n = 130) or regorafenib (n = 20) between September 2021 and January 2024. PNI was calculated as 10 × albumin (g/dL) + 0.005 × lymphocyte count (/mm³). Outcomes included overall survival (OS), progression-free survival (PFS), and radiological response (mRECIST).

Results

A PNI cutoff of 40.6 (sensitivity: 70%, specificity: 61%) stratified patients into high and low PNI groups. High PNI was significantly associated with longer OS in both sorafenib (6 vs. 3.3 months, P < 0.001) and regorafenib (8 vs. 3.7 months, P < 0.01) cohorts. Similarly, PFS was significantly prolonged in high PNI patients (sorafenib: 4.95 vs. 3 months; regorafenib: 7.7 vs. 3.1 months). Multivariate analysis confirmed high PNI and low albumin–bilirubin score (ALBI) score as independent predictors of OS and PFS.

Conclusions

Pretreatment PNI is a reliable, cost-effective predictor of OS and PFS in advanced HCC patients treated with sorafenib or regorafenib. Alongside Child–Pugh and ALBI scores, PNI may help guide personalized treatment strategies by identifying patients most likely to benefit.

Background

The prevalence of antibiotic resistance has become a critical global health concern. In particular, resistant strains of Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) against commonly prescribed antibiotics for various infections are on the rise. These pathogens are frequently implicated in severe and complex infections, e.g., diabetic foot infections (DFI), posing a significant antimicrobial challenges during treatment. Frequently used food grade product, i.e., apple cider vinegar (ACV) carries promising antimicrobial potential. Therefore, the study designed to investigate the potential of ACV in combination with antibiotics to determine the effectiveness of the combination in overall pathogenic burden.

Results

Antimicrobial sensitivity was evaluated using disk diffusion and broth dilution techniques, revealing that at 2.5% acidity, ACV has prominent inhibitory potential against SA and PA. The fractional inhibitory concentration (FIC) index further confirmed synergistic interplay of ACV in combination with antibiotics. The results for minimum bactericidal concentration (MBC) showed when ACV is added to existing antibiotics the MBC value after checkerboard analysis method comes out to be, 128 µg/mL, 128 µg/mL, 64 µg/mL, and 64 µg/mL for amoxicillin, cefotaxime, imipenem, and vancomycin, respectively, against SA whereas concentration of 128 µg/mL, 256 µg/mL, 256 µg/mL, and 128 µg/mL MBC values for respective antibiotics against PA. Quantitative PCR analysis has demonstrated a substantial reduction in the expression of resistance-conferring genes when ACV was combined with antibiotics. Furthermore, molecular docking analysis showed ACV’s active constituents, such as acetic acid and chlorogenic acid, exhibited strong binding affinities against resistant conferring genes and subsequent proteins expression. These findings suggest that ACV may alter permeability of the outer membrane porin channels, thereby improving antibiotic penetration and augmented antimicrobial efficacy.

Conclusion

The study demonstrated that ACV not only improves antibiotic permeability within bacterial cell but also significantly augments bactericidal activity of these agents against resistant strains of SA and PA. The combination of various concentrations of ACV with antibiotics presents an innovative therapeutic strategy to combat current antimicrobial resistance, particularly in the treatment and management of complex DFI. These findings underscore the potential of integrating food grade products with conventional antibiotics to address the growing challenges of antibiotic resistance.

Background

Anemia is a prevalent complication in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), contributing to adverse clinical outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), including dapagliflozin, have demonstrated cardiovascular and renal benefits, with emerging evidence suggesting their role in erythropoiesis and anemia correction.

Methods

This was a prospective cohort study, including patients with T2DM and CKD (stages 3–4). Patients were classified into dapagliflozin and control groups, with further stratification based on baseline anemia status. Outcomes included incident anemia, hemoglobin increase, anemia correction, development of iron deficiency anemia (IDA), and erythropoiesis-stimulating agent (ESA) therapy initiation over a 12-month follow-up.

Results

A total of 255 patients (dapagliflozin: n = 155; control: n = 100) were included, with baseline anemia present in 109 dapagliflozin-treated and 66 control patients. IDA development was higher in dapagliflozin-treated patients (36.7% vs. 18.2%, p = 0.005), occurring exclusively in patients with baseline anemia and more frequently among females. Among non-anemic patients, incident anemia was observed in 11.8% of controls but none in the dapagliflozin group. In anemic patients, a hemoglobin increase ≥ 1 g/dL was more frequent in the dapagliflozin group (66.7% vs. 14.3%, p < 0.001), with a significantly shorter time to response (7.30 vs. 11.57 months, p < 0.001). Anemia correction—defined as achieving hemoglobin ≥ 13.0 g/dL in males or ≥ 12.0 g/dL in females, with a ≥ 1 g/dL increase—was achieved in 53.6% of dapagliflozin-treated patients versus 4.8% of controls (p < 0.001). These findings were consistent in the propensity score-matched cohort, reinforcing the robustness of the observed associations. ESA initiation was lower in the dapagliflozin group (7.3% vs. 24.2%, p = 0.002), with a longer time to therapy initiation.

Conclusions

Dapagliflozin was associated with significant improvements in hemoglobin levels and anemia correction in patients with T2DM and CKD. However, an increased risk of IDA, particularly in female patients, warrants careful monitoring. The protective effects of dapagliflozin against ESA initiation highlight its potential role in anemia management. However, due to the observational design, causality cannot be definitively inferred.

Background

Cervical cancer is the fourth most common cancer among women which remains a significant global health issue, primarily caused by HPV. Standard treatments include surgery, chemotherapy, radiotherapy, and combination of two. However, drug resistance and cancer recurrence are major issues, associated with the treatment failure of cervical cancer. Brassica and Allium vegetables are the rich sources of organosulfur compounds. Previously, natural organosulfur compounds have been evaluated for their antioxidant, anti-inflammatory, anti-proliferative, and apoptosis-inducing actions in different cancer cell lines.

Results

Interestingly, allicin substantially reduced cell viability and migration of cervical cancer cells in a dose-dependent manner. Allicin-treated HeLa cells showed an elevated production of cellular and mitochondrial reactive oxygen species, leading to apoptosis induction. Cellular and nuclear morphological changes clearly indicated that allicin induced apoptosis in cervical cancer cells by activation of caspases. Further, molecular docking studies revealed that allicin showed a high binding affinity to ERK, Snail1, and E-cadherin. Stability of allicin in connection to these protein molecules was evaluated using MD simulation by calculating RMSD, RMSF, RoG, and H-bond values.

Conclusion

Based on experimental evidences and bioinformatic analysis, our findings revealed in-vitro anti-proliferative effects of allicin against cervical cancer cells. However, further, in vivo studies are needed to prove its efficacy in different cancers.

Objectives

Cilostazol is a BCS class-II antiplatelet drug with a wide range of therapeutic actions, including anti-inflammatory, antioxidant, and antiapoptotic properties. Oral administration is associated with poor water solubility, limited absorption, and low bioavailability, which can be overcome by pulmonary administration. Despite of advancements, delivering poorly water-soluble drugs to the lungs with improved solubility, bioavailability, and stability and achieving excellent aerosolization continue to be substantial challenges.

Methods

In this study, cilostazol was formulated as a dry powder inhaler using cyclodextrin metal–organic framework (CD-MOF), i.e., CLZ-CD-MOF by vapor diffusion method. Molecular docking and molecular dynamic simulation confirmed the formation of a cilostazol nanocluster with CD-MOF and its thermodynamic stability.

Results

The free-energy estimation, hydrogen bond analysis, and the presence of CTAB confirmed the thermodynamic stability of cilostazol-CD-MOF with delta G of − 6.4 ± 2 kcal/mol. Compared with CLZ-I formulation, i.e., micronized cilostazol with a DPI InhaLac®500, the cubic-shaped CLZ-CD-MOFs showed excellent aerodynamic performance owing to porous structure and lower density. The solubility of cilostazol significantly increased over a period of 24 h with the CLZ-CD-MOFs. The dissolution study showed that cilostazol was released more rapidly from CLZ-CD-MOFs than from the CLZ-I formulation, i.e., over 90% release within 15 min. The entrapment efficiency of CLZ-CD-MOF was approximately 96.39%. The CLZ-CD-MOF-F3 showed an EC50 value of 32.70 µg /ml in the A549 cell line, suggesting its potential in acute lung injury and pulmonary fibrosis.

Conclusion

Therefore, γ-CD-MOF could be a safe and effective approach for delivering cilostazol to the lungs via dry powder inhalation.

Graphical abstract

Background

Neuroinflammation substantially contributes to the progression of several neurodegenerative illnesses primarily triggered by activated microglia and the release of proinflammatory mediators. Artemisia monosperma, a medicinal herb rich in bioactive compounds, has been studied for its antioxidant and anti-inflammatory effects. This study aims to evaluate the neuroprotective effectiveness of A. monosperma against LPS-induced neuroinflammation in Neuro 2a cells, while also detailing its metabolic profile and antioxidant properties.

Methodology

The neuroprotective potential of A. monosperma methanolic extract has been assessed against LPS-induced neuroinflammation in Neuro 2a mouse neuroblastoma cells line through tracing TLR4 signaling and its related proteins, together with determining inflammatory cytokines and oxidative stress biomarkers. The Folin–Ciocalteu and aluminum chloride techniques were used to measure the extract total phenolics and flavonoid contents, respectively. The triple-time-of-flight tandem mass spectrometry (LC/triple-Q-TOF–MS/MS) coupled with reversed phase high-performance liquid chromatography was used to examine the metabolic profile of the plant.

Results

Artemisia monosperma contained total phenolic and flavonoid contents of 73.85 ± 4.55 μg GA E/mg and 22.38 ± 1.21 µg RE/mg, respectively. Significant antioxidant capacity (FRAP) was shown by A. monosperma extract (341.00 ± 6.34 μM eq/mg) in comparison with Trolox (6.57 ± 0.449 µg/mL). The radical-scavenging efficacy of DPPH (IC₅₀ values of 86.46 ± 2.77 µg/mL) was determined using Trolox as a standard drug. Analysis utilizing (LC-ESI-TOF–MS/MS) of A. monosperma extract revealed 48 hits, mostly polyphenols. Artemisia monosperma extract showed significant neuroprotective effect. This is accomplished by inhibiting TLR4, which reduces neuroinflammatory mediators and the oxidative stress caused by LPS in Neuro 2a mouse neuroblastoma cells. Molecular modeling study highlighted the bis-glycosidic flavones as the top-binding metabolites toward the human myeloperoxidase enzyme capable of competing with the enzyme natural substrate.

Conclusion

These results demonstrate that A. monosperma and/or its active components could be effective protective agents against neuroinflammatory disorders with potential molecular mechanistic activity toward the human myeloperoxidase enzyme, the key contributor to oxidative stress within inflammatory diseases including neurodegenerative conditions.

The in vitro antitubercular activity of a new family of N-substituted indole chalcone analogues against Mycobacterium Tuberculosis H37Rv has been synthesized and evaluated. The synthesis of N-substituted indole chalcone derivatives, namely, 1-(2-oxo-2-phenylethyl)-1H-indole-3-carbaldehyde (S3I1), 1-(2-oxo-2-(p-tolyl)ethyl)-1H-indole-3-carbaldehyde (S3I2), 1-(2-(4-nitrophenyl)-2-oxoethyl)-1H-indole-3-carbaldehyde (S3I3), and 1-(2-(4-methoxyphenyl)-2-oxoethyl)-1H-indole-3-carbaldehyde (S3I4), was achieved by N-substitution of indole-3-carbaldehyde using potassium carbonate in DMSO. Subsequent condensation of these derivatives with various acetophenones led to the synthesis of the corresponding N-substituted indole chalcone derivatives. Notably, within this series of compounds, (E)-1-(4-hydroxyphenyl)-3-(1-(2-oxo-2-phenyl–ethyl)-1H-indol-3-yl)prop-2-en-1-one (S3R3) and (E)-1-(4-bromo-2-hydroxyphenyl)-3-(1-(2-oxo-2-phenyl–ethyl)-1H-indol-3-yl)prop-2-en-1-one (S3R8) exhibited remarkable antitubercular activity, demonstrating minimal inhibitory concentrations values of 06 and 07 µg/mL, respectively. Various spectroscopic methods were used to develop, synthesise, and characterize N-substituted indole chalcone. Hence, newly synthesized N-substituted indole chalcone derivatives act as a promising approach for the design of a new antitubercular moiety with strong antimicrobial agents.

Graphical Abstract