Pakistan journal of pharmaceutical sciences最新文献

Background: Liver fibrosis causes increased mortality rate combined with substantial disabilities throughout the population. The bioactive moieties in purslane promote liver health by shielding hepatic cells while aiding cellular regeneration, by improving overall hepatic functions.

Objectives: The present study examined the nutritional characterization of purslane shoot powder and evaluated its therapeutic effect through bio- evaluation trial.

Methods: 60 male Wistar rats were randomly divided into six groups, namely normal control (NC), bile duct ligation (BDL) induced liver fibrosis groups i.e., (PC, STD, P1, P2 and P3). The STD (Standard Drug Group) received silymarin at 50 mg/kg bw, while other groups received different doses of purslane shoot powder P₃ (1200 mg/kg), P₂ (800 mg/kg) and P₁ (400mg/kg) respectively for 04 weeks.

Results: Purslane shoots exhibited a considerable antioxidant potential in addition to important minerals and fatty acid content. Current intervention reduces serum cholesterol with dose P₃ (1200 mg/kg), followed by P₂ (800 mg/kg) and P₁ (400mg/kg), resulting in 101.0±4.75 mg/dL, 109.9±4.35 mg/dL and 110.1±4.22 mg/dL, respectively. While increase in HDL was also observed as P1 (12.26±0.35), P₂ (13.21±0.39) and P₃ (15.09±0.56) mg/dL, respectively. A remarkable reduction in LFT was observed in experimental group with maximum reduction in P₂ as 135.7±2.38 IU/L for ALP, 41.9±2.09 IU/L for ALT and 93.4±4.67 IU/L for AST, respectively. The results showed a constant reduction in malondialdehyde (MDA) and nitric oxide (NO) levels. Administration of purslane shoot powder significantly showed a marked inclination towards the normalization of all measured biochemical parameters in BDL rats.

Conclusion: Thus, the current study supports that purslane shoot had a curative effect in inhibiting oxidative stress and reducing inflammation in managing liver fibrosis and its associated complications by the activation of hepatic stellate cells.

Background: This study aimed to investigate the relationship between blood uric acid (UA), serum lipoprotein(a) [Lp(a)], and the severity of neurological damage in patients with acute penetrating artery occlusive cerebral infarction combined with type 2 diabetes mellitus (T2DM).

Objectives: To evaluate the role of UA and Lp(a) levels as independent risk factors for neurological damage severity and poor prognosis, and to observe the therapeutic effect of tanshinone.

Methods: Clinical data of patients were analyzed to compare differences in indicators between the mild and moderate groups, as well as between groups with good and poor prognosis.

Results: Patients in the moderate infarction group showed significantly higher levels of UA, Lp(a), and other biochemical markers, along with higher rates of unhealthy lifestyle habits and comorbidities. UA, Lp(a), and infarct diameter were independent risk factors for poor prognosis. Their combined prediction model demonstrated good sensitivity and specificity. Pre-treatment UA and Lp(a) levels were significantly positively correlated with pre-treatment NIHSS scores and post-treatment mRS scores, respectively.

Conclusion: In patients with acute penetrating artery occlusive cerebral infarction combined with T2DM, blood uric acid and serum Lp(a) levels are associated with the severity of neurological damage and serve as independent risk factors for poor prognosis.

Background: Women with hypertensive postpartum syndrome (HDP) are more prone to negative emotions that affect their recovery, while magnesium sulfate has an anti-anxiety effect.

Objectives: This study aims to evaluate the efficacy of magnesium sulfate therapy, administered intravenously or intramuscularly, in preventing complications such as eclampsia and managing blood pressure (BP) in patients with hypertension.

Methods: This research adopted a quantitative research paradigm and participants were assigned to the intervention and the control groups (70 participants each). The control group received their regular postpartum medical care that included antihypertensive medications and health education but did not receive magnesium sulfate treatment and designated physical rehabilitation. The data collected were then sorted and categorized genetically and were analyzed using the SPSS software program version 25.0 to enhance reliability of statistics.

Results: The intervention group demonstrated significant improvements across physical, emotional and functional recovery, including BP compared with the control group. There was significant lowering of both systolic (-20.1 mmHg) and diastolic (-14.2 mmHg) BP, reduced fatigue, improvement in quality of life and decrease in pain (All P < 0.05). A regression analysis confirmed the treatment and health promotion as the positive indicators of the recovery rates while body mass index (BMI) and increased baseline diastolic BP as negative indicators. The convergence of pharmacological and non-pharmacological approaches made postpartum management more effective in terms of short-term as well as extended health problems.

Conclusion: These results are a robust starting off point for the application of a more comprehensive postpartum care framework in clinical care.

Background: Drug addiction is a significant public health issue, with genetic components playing a role in predisposing a person to susceptibility.

Objective: The current study planned to investigate the pathogenic potential of the CHRNA5 D398N (rs16969968) mutation and computationally identify structurally optimized aripiprazole analogs capable of selectively binding the mutant protein.

Methods: PolyPhen-2 and AlphaMissense were used to assess the pathogenic impact of the D398N (rs16969968) mutation in CHRNA5. SwissSimilarity was employed to identify aripiprazole-like structural analogs for therapeutic screening. The chemical structures of selected analogs were drawn and optimized using ChemDraw. SwissADME was used to evaluate pharmacokinetic properties, including drug-likeness and absorption parameters. Molecular docking was performed to estimate the binding affinity of candidate ligands toward the mutant CHRNA5 protein, while Density Functional Theory (DFT) analysis was conducted to determine their electronic, reactive, and electrostatic properties for final lead selection.

Results: Functional prediction tools, including PolyPhen-2 and Alpha Missense, predict the mutation to be pathogenic with high scores predicting deleterious effects. Structural modeling with AlphaFold showed conformational changes in the mutant CHRNA5 protein, especially at the active site, validated with structural alignment. For therapeutic potential, 20 structurally similar aripiprazole ligands were identified through Swiss Similarity. Molecular docking indicated ligand 12 and ligand 4 had the highest binding affinity for mutant protein (-3.034 and -2.774 kcal/mol, respectively). PyMOL visualization indicated ligand-receptor interactions. ADMET analysis predicted good pharmacokinetics: Ligand 12 indicated high gastrointestinal absorption and CYP non-inhibition, while ligand 4 was a non-P-gp substrate with good solubility. DFT analysis indicated ligand 4 was the most polar, while ligand 12 was the most chemically reactive.

Conclusion: These findings imply the D398N mutation predisposes to addiction susceptibility and that ligand 12 holds promise as a therapeutic target due to its high binding affinity and good pharmacological profiles.

Background: Galactorrhea, an abnormal milk secretion, is frequently triggered by medications that influence prolactin levels.

Objectives: This study aimed to identify high-risk drugs for drug-associated galactorrhea (DAG) and explore their characteristics using data from the FDA Adverse Event Reporting System (FAERS).

Methods: We analyzed 6,195 DAG reports by applying four disproportionality analysis algorithms (ROR, PRR, MGPS, BCPNN) to detect positive signals.

Results: The analysis of 6,195 reports showed that DAG was most prevalent in patients aged 20-40 years, with a slight male predominance (55.52%). Oral medications were the primary cause (68.99%). A total of 32 drugs were strongly associated with DAG, with antipsychotics being the most frequently implicated class (N = 12), followed by antidepressants (N = 7) and hormone-related drugs (N = 6). Risperidone had the highest risk (ROR = 346.71) and report count (N = 3,378).

Conclusion: This study provides a comprehensive list of high-risk drugs for DAG, offering critical data to guide safer prescribing and improve pharmacovigilance. Clinicians should be vigilant in monitoring for suggestive symptoms like galactorrhea, amenorrhea and sexual dysfunction, especially in high-risk individuals on long-term treatment with prolactin-elevating medications. These findings underscore the importance of patient safety and inform clinical practice.

Background: Despite the established role of anti-vascular endothelial growth factor (anti-VEGF) agents as first-line therapy for diabetic macular edema (DME), their therapeutic effect may be incomplete or unsustained in a proportion of patients.

Objectives: This study aimed to evaluate the efficacy and safety of intravitreal conbercept (IVC) combined with traditional Chinese medicine (TCM) for the treatment of DME.

Methods: A systematic search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library, Scopus, and CNKI from database inception to June 2025. Eligible randomized controlled trials (RCTs) comparing IVC combined with TCM versus IVC monotherapy were included.

Results: A total of 14 studies involving 979 patients met the inclusion criteria. Compared with IVC monotherapy, IVC combined with TCM resulted in a greater reduction in central macular thickness (CMT) and significantly improved best-corrected visual acuity (BCVA) at both 3 and 6 months. However, no significant difference in BCVA was observed at 1 month (MD = -0.03; 95% CI -0.08 to 0.03; p = 0.34). The combination therapy was also associated with a significantly lower ineffectiveness rate (RR = 0.32; 95% CI 0.22-0.47; p < 0.05) and fewer adverse events (AEs) (RR = 0.67; 95% CI 0.45-1.00; p < 0.05).

Conclusion: IVC combined with TCM may provide additional therapeutic benefits for patients with DME without increasing safety risks. Nevertheless, high-quality, large-scale, multicenter RCTs are still required to further confirm these findings.

Background: Paclitaxel is used in oral cancer treatment, but drug sensitivity remains a concern. CHFR has been implicated in tumor regulation, yet its role in modulating paclitaxel sensitivity in oral cancer requires further investigation.

Objectives: This study aimed to evaluate the effect of CHFR on enhancing the drug sensitivity of paclitaxel in oral cancer cells.

Methods: A rat oral tumor model was established, followed by paclitaxel intervention. Observations included tongue tissue morphology, immune function, cell cycle, apoptosis, and the expression levels of NF-κB and CHFR proteins and mRNAs.

Results: The modeling success rate was 100%, with visible tongue masses and ulceration. CHFR protein expression increased in the CHFR mimic group. The high-dose paclitaxel group showed the highest immune indices, increased G0/G1 phase cell proportion, and significantly decreased tumor cell viability. The CHFR mimic group exhibited the smallest tumor volume, marked tumor cell death, and active proliferation. CHFR downregulated NF-κB expression; CHFR mRNA was higher, and NF-κB mRNA lower, compared to the high-dose paclitaxel and CHFR mimic groups.

Conclusion: CHFR enhances paclitaxel sensitivity in oral cancer cells by downregulating NF-κB, effectively inhibiting tumor cell activity and suppressing tumor progression.

Background: The quality of heparin-anticoagulated specimens is of paramount importance for the delivery of highly accurate diagnostic results in neurorespiratory settings. However, pre-analytical factors such as hemolysis, clotting, and labeling errors often threaten this quality. This paper explores if the use of a Plan-Do-Check-Act cycle management would improve the quality of the heparin anticoagulation specimen.

Objectives: To evaluate the effectiveness of managing the PDCA cycle to improve the quality of heparin anticoagulation specimen samples in a neurorespiratory care unit through error reduction and work process optimization.

Methods: This was a pre-post intervention study that took place in the 47-bed neuro-respiratory care unit of Shanghai Sixth People's Hospital. A total of 2,000 samples were screened from June 2020 to June 2021. Overall, 108 samples (54 pre-PDCA implementation and 54 post-PDCA implementation) were selected for analysis of specimen quality, delivery time, and pre analytical errors. Employee training was carried out, as well as process improvement through regular audits. Data collection took place in terms of specimen quality, delivery times, staff compliance, and staff knowledge from January to March 2023, with intervention phases from April to June 2023.

Results: Following the PDCA intervention, there was a great improvement in specimen quality, with the percentage of qualified specimens rising from 68.5% to 94.4% (p < 0.001). Hemolysis decreased from 18.5% to 3.7% (p < 0.001), clotting from 11.1% to 1.9% (p < 0.001), and incorrect labeling from 9.3% to 0%. Mean delivery time reduced from 53.4 ± 11.8 minutes to 34.6 ± 7.3.

Conclusion: A substantial improvement in the quality of anticoagulation specimens of heparin was achieved through the effective management of the PDCA cycle. It is evident that the PDCA cycle method possesses beneficial applications in optimizing laboratory practices for ensuring patient safety in neurorespiratory care units.

Background: Severe brain injury patients often require effective analgesia and sedation to manage pain, agitation, and inflammatory responses, which can impact clinical outcomes.

Objectives: This study aimed to analyze the effects of ketamine combined with remifentanil on analgesic sedation and inflammatory factors in patients with severe brain injury.

Methods: Sixty patients were randomly divided into a remifentanil-only control group and a ketamine combined with remifentanil group. VAS, SAS, BCS, Ramsay scores, inflammatory factors (TNF-α, IL-2), and adverse reactions were compared.

Results: Compared with pre-operative levels, both groups showed significant reductions in VAS, SAS scores, TNF-α, and IL-2 (P < 0.05). Compared with the control group, the combined group exhibited significantly lower VAS and SAS scores, higher Ramsay sedation and BCS scores, and lower TNF-α and IL-2 levels (P < 0.05). There was no statistically significant difference in adverse reactions between groups (P > 0.05).

Conclusion: Ketamine combined with remifentanil provides better analgesic and sedative effects in severe brain injury patients, effectively reducing pain and agitation, improving comfort, and suppressing inflammatory responses, demonstrating good clinical application value.

Background: Chronic insomnia impairs health-related quality of life and current pharmacotherapies carry substantial adverse-effect profiles, prompting the search for safer multi-target interventions. Kong Sheng Pillow Zhongdan (KSPZ), a classical herbal formula, is empirically used for sleep disturbance, yet its molecular basis remains unclear.

Objectives: To elucidate the putative mechanisms of KSPZ against chronic insomnia through a network-pharmacology approach and to prioritise targets for experimental validation.

Methods: Active compounds were retrieved from TCMSP, HIT2.0 and TCMIP and filtered by oral bioavailability ≥30% and blood-brain barrier permeability ≥-0.3. Insomnia-related genes were collected from DisGeNET, GeneCards and OMIM. Overlapping targets defined the "core prescription-insomnia" interactome (126 genes). Protein-protein interaction networks were constructed with STRING and hub nodes identified by CytoHubba. GO, KEGG and Reactome enrichment analyses were performed with clusterProfiler; key ligand-target pairs were evaluated by AutoDock Vina. A drug-ingredient-target-disease network was visualised in Cytoscape.

Results: Twenty-eight bioactive compounds (e.g., quercetin, kaempferol, luteolin) were mapped to 126 shared targets enriched in neuro-inflammation (IL-17, TNF, NF-κB), serotonergic and dopaminergic synapses, circadian rhythm and cAMP signalling. Top hub genes included TNF, IL6, AKT1, PTGS2, BDNF and DRD2. Molecular docking showed high affinities (ΔG ≤ -8.5 kcal mol^-¹) for quercetin-GABRA1, kaempferol-HTR2A and luteolin-BDNF complexes, supporting modulatory effects on inhibitory/excitatory neurotransmission and neuroplasticity.

Conclusion: KSPZ exerts multi-level effects on neuro-immune regulation, inflammation and circadian pathways, providing a rational basis for its empirical use in chronic insomnia. In-vivo validation of the predicted neurotransmitter and cytokine targets is warranted to translate these network findings into clinical applications.