Future Journal of Pharmaceutical Sciences最新文献

Background

Eczema remains a challenging dermatological condition affecting millions worldwide and current treatments often present limitations and side effects. Dodder or Cuscuta reflexa has documented anti-inflammatory, antioxidant, and antimicrobial properties that may benefit skin conditions. The goal for this study was to develop and optimize a novel topical hydrogel with anti-eczema activity using C. reflexa extract for eczema management. Evaluation parameters included physicochemical characterization like viscosity, pH, spreadability, in vitro drug release, ex vivo permeation, skin irritation, and in vivo efficacy using DNCB-induced eczema model.

Results

The hydrogel was formulated using varying concentrations of Carbopol 934 as the gelling agent. Response surface methodology optimized the formulation, yielding ideal physicochemical properties: viscosity (14,872 cP), pH (6.32), and spreadability 76%. In vitro studies demonstrated sustained release with 64.00% cumulative release over 14 h. Ex vivo permeation study optimized formulation showed 9% permeation and 48% retention in 4 h. Skin irritation study indicated that the optimized hydrogel formulation is safe for topical application without causing skin irritation. In vivo evaluation in an eczema model induced by 2,4-dinitrochlorobenzene (DNCB) in ICR mice showed significant improvement in clinical symptoms and histopathological parameters.

Conclusion

The developed C. reflexa hydrogel formulation represents a promising natural alternative for eczema management, demonstrating optimized formulation, exhibits favorable physicochemical properties, sustained release characteristics, and therapeutic efficacy in eczema models.

Graphical Abstract

Background

Migraine is a neurological disorder and major cause of disability globally, especially in women and young adults. This study aimed to investigate the beneficial effects of polydatin (PD), a natural compound, against nitroglycerin (NTG) induced migraine like headache in mice.

Materials and methods

Behavioural paradigms included Von Frey filament test, tail flick test, light aversion test and assessment of migraine-associated pain like behaviour. In addition, biochemical investigations were undertaken to determine the effect of PD on migraine associated markers including oxidative stress, nitric oxide (NO) and calcitonin gene related peptide (CGRP). Integrated in vivo, in silico, and network pharmacology approaches were employed to evaluate PD’s antimigraine effects. Statistical significance was set at p < 0.05.

Results

Treatment with PD attenuated NTG-induced migraine like headache and related behavioural changes. PD-subjected animals exhibited enhanced levels of catalase, glutathione-S-transferase, and glutathione, as well as reduced lipid peroxidation, compared to NTG-only treated animals. Reduction in CGRP and nitrite levels along with reduced expression of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was also observed in mouse cortex and trigeminal nucleus caudalis (TNc) after treatment with PD compared with disease controls. Histological sections from PD treated animals from these regions resembled closely with those of controls with improved cell viability. Molecular docking studies suggested that PD docked in the similar binding pocket as that of CGRP, Rimegepant (a CGRP receptor blocker) and Sumatriptan. Network pharmacology revealed potential interaction of hub genes with PD, with proteins like NOS1 (nNOS), NOS2 (iNOS), NOS3, PDE5A, GATM, ARG1 and ARG2 having significant role in network functionality and the potential mediation of PD therapeutic effect.

Conclusion

PD ameliorated NTG-induced migraine like headache through modulation of NO, CGRP and oxidative stress dependant mechanisms.

Background

The genus Cynanchum, family Apocynaceae is a group of climbing vines that have long been in folk medicine used as antitussives, analgesics, anticonvulsants, expectorants, diuretics, antifebriles, and tonics.

Results

Cynanchum acutum crude extract was investigated to determine its chemical composition through LC-ESI-TOF-MS/MS technique, where 46 hits were observed. Among these compounds, quercetin-3-O-β-galactoside was previously reported within the plant as a major component. This compound was isolated and purified using different chromatographic techniques, and its concentration was estimated using high-performance thin-layer chromatography (HPTLC). Two semi-synthetic derivatives were synthesized from this compound, namely 7-benzyl- and 7-bromoethyl quercetin-3-O-β-galactosides. Both analogs, which are more hydrophobic, were developed as an attempt to improve the physiochemical properties and, in turn, the pharmacokinetics of the parent compound. Our study also includes the determination of antiviral activity against COVID-19 of Cynanchum acutum crude extract along with quercetin-3-O-β-galactoside in addition to the two semi-synthesized derivatives. The antiviral assay revealed that the synthetic benzyl derivative of quercetin-3-O-β-galactoside demonstrated promising activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The potential molecular aspects of the parent and semi-synthetic analogs were highlighted through molecular modeling simulation of docking the compounds at the viral main protease (Mpro) binding pocket. In silico findings demonstrated significant affinity and residue-wise binding interactions in relation to the co-crystallized small molecule Mpro inhibitor.

Conclusion

Collectively, our study adds to the current knowledge of SARS-CoV-2 pharmacotherapy by introducing drug-like small molecules with potential activity profiles.

Graphical abstract

Background

The oral route is the recommended route of administration of most therapeutic drugs. Unfortunately, due to swallowing difficulties especially for elderly and young patients, conventional oral dosage forms have low patient compliance. To overcome these difficulties, orally disintegrating tablets (ODTs) were presented in this work.

Results

In this study, the solubility of rivaroxaban (RXB) was enhanced using nano mixed micelles (NMMs). The optimum NMM formula was selected according to the highest drug content (8.00 ± 0.02 mg), clarity upon reconstitution, smallest particle size (PS) (161.50 ± 2.50 nm), lowest polydispersity index (PDI) (0.37 ± 0.01), and optimum zeta potential (ZP) (− 16.13 ± 0.42 mV). The optimized formula was then mixed with different ODT carriers (gellan gum, sodium alginate, and hydroxypropyl methylcellulose) and freeze dried. The ODTs were evaluated via weight variation, thickness and diameter, friability, drug content, in vitro disintegration, swelling profile, in vitro dissolution. The tablet containing 35 mg sodium alginate (SA) and 15 mg gellan gum (GG) was found to fulfill the optimum criteria for ODTs. The in vitro disintegration profile of tablets was evaluated in six human volunteers, revealed a disintegration time ranging from 31.5 ± 1.89 s to 85 ± 3.54 s.

Conclusion

A promising ODT formulation containing RXB-loaded NMMs has been successfully developed, offering a suitable option for special populations such as the elderly and children who experience difficulty swallowing. This advancement may enhance treatment effectiveness by improving patient compliance.

Nanoparticles have gained prominence in the formulation of nanopesticides, leveraging their unique nanocharacteristics. This study delves into the nephrotoxic implications of CuONanoSheet (CuONS), as nanopesticide tailored for agricultural applications to understand its safety and viability in this field. The nanocharacterization of CuONS was meticulously examined using X-ray diffraction, high-resolution transmission electron microscopy, field emission scanning electron microscopy and Zeta-Sizer device, which assessed zeta-potential, hydrodynamic size, and polydispersity index. Rats treated with CuONS showed elevated levels of blood urea nitrogen, creatinine, and uric acid and a significant increase in lipid peroxidation (MDA) and reduced levels of antioxidant enzymes. CuONS treatment resulted in an imbalance in pro-apoptotic Bax and anti-apoptotic B-cell lymphoma2 (Bcl2) levels. Histologically, CuONS induced glomerulus degeneration and vacuolation in tubules lining epithelium. Immunohistochemical evaluations revealed strong expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), tumor necrosis factor-alfa (TNF-α), and the tumor suppressor gene (p53) in CuONS-treated kidneys. Ultrastructural assessments further confirmed these structural abnormalities. While CuONS exhibits potential as a nanopesticide, caution is warranted due to observed negative impacts on kidney functions, and histological architecture, in this study. Careful consideration of potential side effects on other living organisms is imperative in the utilization of CuONS in agricultural practices.

Background

Ebola virus (EBOV) causes severe hemorrhagic fever outbreaks with high mortality rates, and currently there are no approved antiviral drugs. In this study, in silico (computational) techniques were applied to evaluate six small-molecule inhibitors—Latrunculin A, LJ001, CA-074, CA-074Me, U18666A, and Apilimod—focusing on drug-likeness, ADMET profiles, molecular docking, quantum chemical descriptors, and molecular dynamics simulations.

Results

Among the tested compounds, CA-074 proved to be the most promising candidate as it exhibited strong binding affinity to Cathepsin B (− 40.87 kcal/mol), an endosomal cysteine protease crucial for Ebola virus entry, as well as favorable ADMET properties and safety indicators such as absence of the human Ether-à-go-go-Related Gene (hERG) inhibition and mutagenic potential. CA-074 fulfilled the Lipinski and Veber rules with low plasma protein binding and a high unbound fraction, indicating improved bioavailability. The quantum descriptors indicated high chemical stability and low reactivity. Molecular dynamics confirmed the stability of the CA-074–Cathepsin B complex over 300 ns, with persistent hydrogen bonds and low flexibility in the binding pocket.

Conclusion

CA-074 has the potential to be a leading candidate for the treatment of EBOV. The comprehensive in silico strategy provides a valuable framework for accelerating early-stage antiviral drug discovery.

Background

Hepatocellular carcinoma (HCC) represents 90% of primary liver cancers and is the fourth leading cause of cancer-related death worldwide. Sorafenib remains the standard first-line systemic therapy for advanced HCC, though real-world outcomes vary from clinical trial results. We aimed to evaluate survival outcomes and identify prognostic factors in HCC patients receiving sorafenib in routine clinical practice over an 18-month follow-up period in a real-world clinical setting.

Methods

An ambispective cohort study (integrating retrospective and prospective data) was conducted involving 347 patients with confirmed primary HCC treated with Sorafenib between June 2023 and January 2025, of whom 292 had complete 18-month follow-up and were included in the survival analysis. Clinical data, laboratory markers, imaging Response Evaluation Criteria In Solid Tumors (RECIST 1.1), adverse effects, and treatment modifications were analyzed. Kaplan–Meier analysis and Cox regression models were used to determine overall survival (OS), progression-free survival (PFS), and prognostic predictors.

Results

The observed OS rates at 6, 12, and 18 months were 69.3%, 45.2%, and 31.1%, respectively. Corresponding PFS rates were 58.6%, 36.9%, and 24.8%. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status ≥ 1, AFP > 400 ng/mL, Albumin-Bilirubin (ALBI) grade 3, and vascular invasion were significantly associated with reduced OS (p < 0.05). Patients who achieved partial response or stable disease per RECIST were more likely to continue Sorafenib beyond 6 months. Toxicity was generally tolerable, with a low rate of permanent treatment discontinuation.

Conclusion

Sorafenib continues to demonstrate efficacy in real-world practice as first-line therapy for advanced HCC, with clear clinical and biochemical indicators, including ALBI grade, AFP, ECOG, and early radiological response, serving as key prognostic factors of treatment success. Early response assessment with identification of poor prognostic factors is critical for optimizing outcomes, and proactive toxicity management can improve outcomes in real-world settings.

Background

The efficacy of synthetic drugs in the treatment of diabetes mellitus often falls short, limiting their use to symptom management. Consequently, there has been an increasing fascination with alternative medicine, specifically herbal remedies. The presence of alkaloids in medicinal plants presents a promising prospect for the advancement of novel approaches to diabetes mellitus therapies. The aim of this research is to evaluate the bioactive alkaloid phytoconstituents and their interaction with the α-amylase and α-glucosidase inhibitors using in-silico approach.

Results

A total of 49 phytoconstituents were analyzed as potential inhibitors of these enzymes with top 15 selected based on molecular docking studies. Physicochemical properties, ADME (absorption, distribution, metabolism, and excretion) profile, and toxicity predictions were performed to predict pharmacokinetics, drug-likeness, and toxicity. Subsequently, the molecular docking study was performed using Schrodinger software (PDB ID: 3TOP). Piperumbellactam C (− 8.18 kcal/mol) and Trigonelline (− 7.99 kcal/mol). displayed the highest docking score and standard acarbose showed (− 8.97 kcal/mol). The MM-GBSA (Molecular Mechanics, General Born Surface Area) assay showed favorable binding energy. All other phytoconstituents exhibited favorable pharmacokinetic and toxicological parameters and found within acceptable ranges. Further, a 200 ns MD (Molecular Dynamic) Simulation study was carried out in order to check the stability of Piperumbellactam C-3TOP complex.

Conclusions

The findings of this research validate the antidiabetic properties of some active alkaloid phytoconstituents and additionally showcase the potential inhibitory activity via in-silico analysis.

Background

Today brain tumors are the most life-threatening diseases which universally have a high death rate and reported as a second leading cause of death in not only adults but also children. Several medicinal approaches have been utilized to treat tumors, but the recommended methods had some limitations. Numerous phytoconstituents isolated from various medicinal plants have been reported to have anticancer property, but there are some major reasons for the clinical failure of these compounds such as its poor solubility, bioavailability and tissue distribution and poor absorptivity in the body. Thus, there is a strong need to design the best treatment to cancer cells with great efficiency, less side effects and with promising approach for the delivery strategies. Nanotechnology is proved to be a bridge to overcome the limitation of conventional therapies of drug administration and distribution in the cancer treatment. In the present study, curcumin- and 6-gingerol-based nanoemulsion (CGNE) has been successfully develop and characterized.

Result

The FTIR spectroscopy of CGNE exhibits typical spectra of both curcumin and 6-gingerol. The pH of CGNE was found to be acidic, and the refractive index value of formulated CGNE was found to be 1.38, indicating the isotropic nature of drugs. Percentage transmittance of nanoemulsion was close to 100%. Zeta potential of optimized nanoemulsion was found to be –29 mV. During ex-vivo drug diffusion studies, 48.4% and 78% diffusion of curcumin and 6-gingerol, respectively, were observed from CGNE at the end of 6 h, and followed the anomalous release mechanism.

Conclusion

The drug release mechanism of the formulated CGNE was calculated by using the Korsmeyer–Peppas equation, and the diffusion exponent ‘n’ for curcumin and 6-gingerol indicated the anomalous release mechanism. In vitro cytotoxicity against the human glioblastoma cell line U373-MG, study demonstrated that the combination of curcumin- and 6-gingerol-based nanoemulsion showed the synergistic result of cell growth inhibition.