Future Journal of Pharmaceutical Sciences最新文献

Background

Cachexia, a loss of appetite and body weight as a result of systemic inflammation, considered one of the unavoidable side effects of radiation therapy. Controlling ghrelin (Ghr) levels could assist in alleviating this condition by improving appetite, promoting energy storage, and reducing cytokines’ generation. This study aimed to explore the effect of Biochanin A (BCA), a natural bioactive isoflavone, in alleviating radiation-cachexic syndrome.

Results

Molecular docking study of BCA demonstrated strong fitting with more binding interactions than megestrol acetate (MA), a commonly prescribed medication for cachexia, into Ghr active binding site. Accordingly, irradiated rats were treated with BCA or MA, with body weight monitoring. Force swimming test (FST) was carried out followed by gastrocnemius muscle weighting and histological examination. Biochemical assay of Ghr, TNF-α, insulin growth factor-1 (IGF-1), myostatin (Mst), lactate dehydrogenase (LDH), and brain serotonin (5-HT) level, were carried in order to estimate the possible action pathway of BCA. Results showed that BCA improved weight gain and histological muscle bundle arrangement. Although, BCA and MA significantly reduced serum TNF-α by 25.6% and 24.2%, respectively, only BCA maintained normal IGF-1and Mst levels, whose balance is necessary to avoid skeletal muscle loss, the main mark of cachexia. Moreover, BCA showed tissue injury mitigation with normal energy expenditure by significantly suppressing LDH (20.5%) and maintaining normal 5-HT level.

Conclusion

By preserving the appropriate IGF-1 and MST metabolic balance and keeping muscle homeostasis, BCA, with its high Ghr binding interaction and anti-inflammatory properties, could have an impact on radiation cachectic syndrome.

Background

The risks of heart disease, resistance of insulin, and diabetes mellitus type II are increased in individuals diagnosed with metabolic syndrome. Furthermore, there is an increase in the vascular and neurological effects. This study aimed to assess the isolated independent impact of hepatitis C virus (HCV) on metabolic syndrome, excluding obesity and diabetes mellitus as common risks, this impact was assessed using the metabolic syndrome Severity Z-score (MetS Z-Score) which was initially designed to assess metabolic disease severity itself. Fifty-one HCV patients non-obese and non-diabetic who visited the Tropical Medicine Department from July 2023 to June 2024 were included in our prospective cross sectional study.

Results

After calculation of MetS Z-Score, strong correlations were observed between MetS Z-score and the following data: HDL, fasting insulin, fasting blood sugar, HOMA-IR and hypertension (P value < 0.05). Moreover, The MetS Z-Score was found to have higher values in hypertensive patients. Jaundice shows a near to significance correlation with the MetS Z-Score. Anemia, hypoalbuminemia and thrombocytopenia were observed in the included HCV patients. Low density lipoprotein, alanine aminotransferase, aspartate aminotransferase, cholesterol and triglycerides have shown higher levels than normal in the included HCV patients.

Conclusion

The MetS Z-score can be used for determining the severity of metabolic abnormalities in HCV patients who are neither diabetic nor obese.

Background

Vildagliptin (VLG), an antidiabetic agent, presents a potential solution to this widespread affliction. It exhibits notable attributes, such as a high solubility and a shorter elimination half-life. The current study uses a microreactor to fabricate sustained-release VLG-encapsulated cross-linked chitosan–dextran sulfate nanoparticles (VLG-CDNPs). The fabrication was systematically optimized using the design of experiment approach.

Results

The optimized VLG-CDNPs had an average particle size of 217.4 ± 12.3 nm and an encapsulation efficiency of 78.25 ± 3.0%. Scanning electron microscopy revealed that the nanoparticles had a smooth spherical shape. Spray drying was used for drying, and the reconstitution ability was close to ideal (~ 1.33). In vitro studies revealed sustained VLG release over 12 h, with ~ 58% in acidic and ~ 83% in basic conditions. Cell viability remained at 80% even at 100 μg/mL, and glucose uptake in L6 cells was significantly enhanced with VLG-CDNPs (78.34%) compared to pure VLG (60.91%). VLG-CDNPs also showed moderate inhibitory activity against α-amylase (41.57%) and α-glucosidase (63.48%) compared to pure VLG, which had higher inhibition levels.

Conclusion

The study’s outcome suggested that the optimized VLG-CDNPs  may serve as an effective and promising nanoformulation for managing diabetes mellitus.

Background

Acute coronary syndrome (ACS) patients are vulnerable to anxiety and depression. This study aimed to assess the mental health burden among Egyptian ACS patients by assessing the prevalence and associates of these conditions. This study enrolled 212 patients who underwent coronary angiogram. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Demographic, psychosocial, and clinical data were collected. Univariate and multivariate logistic regression analyses identified factors associated with anxiety and depression.

Results

The mean age of the participants was 54.1 years, and 80.7% were males. More than half (58.1%) exhibited anxiety, depression, or both, with depression being more prevalent than anxiety (48.1% vs 38.2%). Past major depressive disorder was strongly correlated with both anxiety and depression. Higher anxiety scores increased the odds of depression (OR = 1.234, p < 0.001), and vice versa (OR = 1.55, p < 0.001). Hypertension and the use of antihypertensive medications were associated with increased depression. Significant associates of anxiety included increased heart rate, past use of furosemide and enoxaparin, and current polypharmacy.

Conclusions

A substantial proportion of ACS patients experience comorbid anxiety and depression. Polypharmacy, past depression, and hypertension are key risk factors. Targeted interventions addressing these factors are essential for improving mental health in this vulnerable population.

Background

Diabetes mellitus affects millions globally, necessitating effective management strategies. Glenmark Pharmaceutical Limited introduced a fixed-dose combination of teneligliptin and dapagliflozin in 2022 to address this need. However, existing methods for their simultaneous detection are limited, lacking forced degradation studies essential for assessing drug stability.

Results

A stability-indicating RP-HPLC method was developed for the simultaneous determination of dapagliflozin and teneligliptin in pharmaceutical formulations. The separation was efficiently achieved employing a Zorbax Eclipse Plus C18 column (150 mm × 4.6 mm, 5 µm). The mobile phase comprised a mixture of 10 mM ammonium acetate buffer in water, methanol, and acetonitrile in a suitable proportion and delivered at a flow rate of 0.6 mL/min. Detection of the isocratic eluents was performed at 224 nm using a photodiode array (PDA) detector. Validation against various stress conditions, as per ICH guidelines, revealed significant degradation of teneligliptin primarily under acidic, basic, and oxidative stress. Moreover, liquid chromatography tandem mass spectrometry (LC-MS/MS)-based characterization was conducted for the primary degradation products of teneligliptin generated under acidic, basic, and oxidative conditions.

Conclusions

The developed RP-HPLC method with a stability-indicating approach provides an efficient means for the simultaneous determination of dapagliflozin and teneligliptin in pharmaceutical formulations. The significant degradation was observed under various stress conditions and also successfully separated the degradation products by this method. The proposed method directly applied for the characterization of degradation products and based on LC-MS/MS data the structure of degradation products was generated and also degradation pathways under various stress conditions were predicted. The proposed method ensured accurate and precise results in quality control process in pharmaceutical industry, and adherence to ICH validation guidelines affirms its reliability in assessing the stability of these compounds.

Background

Chronic inflammation is an increasing global healthcare challenge with limited effective treatment options. Developing medications for chronic diseases requires high financial investment and a long duration. Given these challenges, alternative strategies are needed. Here, we focus on one such strategy that holds great promise: drug repurposing, which involves identifying new therapeutic uses for existing drugs.

Main body

Here, we discuss the importance of two key transcription factors: nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), in orchestrating complex pathophysiological signaling networks involved in chronic inflammatory diseases. Dysregulation of the NF-κB and AP1 signaling pathways have been associated with various diseases, such as cancer, inflammatory disease, and autoimmune disorders. This review emphasized that repurposed small-molecule inhibitors of these pathways have proven successful as therapeutic interventions. These compounds exhibit high degrees of specificity and efficacy in modulating NF-κB or AP-1 signaling, making them appealing candidates for treating chronic inflammatory conditions. This review discusses the therapeutic potential and action mechanisms of several repurposed small-molecule inhibitors for combating diseases caused by abnormal activation or inhibition of NF-κB and AP-1.

Conclusion

This concise review highlights the potential of repurposing small-molecule inhibitors targeting the NF-κB and AP-1 pathways as effective therapies for various chronic inflammatory diseases. While further experimental validation is needed, drug repurposing offers a promising strategy to bypass the existing lengthy and expensive new drug development processes, providing a faster and more economical route to novel treatments.

Background

Endogenous substances of krill oil (KO) are lipophilic in nature and have clinical significance viz. DHA/EPA, phospholipids and astaxanthin. To improve the nanodispersibility of endogenous substances of KO, a self-nanoemulsifying system (SNE) was developed.

Results

Ternary phase behaviour of KO was explored in ethanol (ET); propylene glycol, (PG); and PEG600 using Tween80 and Tween20 as surfactants. PEG600 induced the self-nanoemulsification of KO and yielded one phase region (OPR); dilution lines (KO/Smix fraction containing PEG600) traversed across OPR, produced a fully dilutable nanoemulsion system. PEG600-based nanoformulations (NFs) of KO underwent phase transformation via percolation behaviour in nanostructure domains (86–207 nm). PEG600 induced ternary phase behaviour of KO as revealed from rheological data (higher eta values), refractive index (nonlinear) and conductivity (bimodal) patterns. Induced phase transformation could be an interaction between aqueous phase and KO/Tween20 in PEG600 environment; generating highly viscous domains of low electrical conductivity. NFs offered antioxidant activity over corresponding coarse systems (p < 0.01) as measured using DPPH method. Optimized NFs (F4 and F6) inhibited the growth of skin cancer cell line (A431) in the range of 100–500 × dilutions.

Conclusion

Phase behaviour of KO was induced by PEG600, transforming the dilution pattern via generation of one phase region; however, ethanol and propylene glycol as co-solvents did not. PEG600-based NFs of KO possessed antioxidant as well as cytotoxic to skin cancer cell lines (A431).

Background

The exact pathogenesis of Huntington’s disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats.

Methods

Sixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters.

Results

Lisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2.

Conclusion

Notably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD.

Background

Infections caused by biofilm-forming bacteria have significantly linked to dental plaque and caries. The aim of this study is to assess efficacy of some natural compounds in inhibition and eradication of biofilm formed by bacterial isolates from dental infections.

Results

Bacterial isolates were recovered from dental plaque/caries and identified using standard microbiological tests and 16S rDNA sequencing. The isolated bacterial strains include Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Klebsiella pneumoniae, and Escherichia coli. The antibiotic susceptibility was determined by disk diffusion method and revealed that the majority of isolates showed high antibiotic resistance, and 61% of isolates were found to be multidrug resistant. The biofilm formation capacity of isolates was investigated using microtiter plate assay. Among the 77 bacterial isolates, seventeen showed moderate biofilm formation capacity, twenty-two showed near-moderate, thirty-four had weak biofilm-forming capacity, and four were non-biofilm producers. The antibiofilm activity of tested compounds (rose and jasmine oils, propolis, vanillin, and vinegar) was evaluated against isolates with highest biofilm-forming capacity. The in vitro antibiofilm ability of tested substances were investigated alone or in combination with each other to evaluate their ability to prevent biofilm formation or destroy preformed single-/multispecies biofilms. Finally, antibiofilm ability of tested combination was evaluated ex vivo on natural teeth. Our results showed that vanillin in combination with rose or jasmine oils showed promising biofilm inhibition and biofilm eradication activities in both the in vitro and ex vivo models.

Conclusions

Dental plaque and caries can be successfully prevented using combination of vanillin with rose or jasmine oils, and these compounds can be incorporated in new anticaries dental formulations.