The present study investigated the therapeutic potential of quercetin nanoparticles (QNPs), administered alone or in combination with levodopa/carbidopa (L/C), against reserpine-induced neurochemical alterations and motor dysfunction in a rat model of Parkinson's disease (PD). Animals were randomly assigned to five experimental groups: a control group, a reserpine-induced PD group, and PD groups treated with QNPs, L/C, or their combination. Motor performance was assessed using the open-field and grid traction tests. Reserpine administration induced marked motor impairments accompanied by significant reductions in dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels in both the striatum and midbrain. These neurochemical deficits were associated with elevated monoamine oxidase (MAO) activity, increased lipid peroxidation (malondialdehyde, MDA), enhanced acetylcholinesterase (AChE) activity, and increased nitric oxide (NO) levels in both brain regions. Additionally, reduced glutathione (GSH) levels were decreased in the midbrain but elevated in the striatum. Treatment with QNPs significantly restored monoamine levels and normalized MAO and AChE activities. Moreover, QNPs markedly attenuated oxidative stress and improved motor performance in reserpine-treated rats. Similarly, L/C administration effectively reversed monoamine depletion, normalized enzymatic activities, and mitigated oxidative stress. Notably, combined treatment with QNPs and L/C produced effects comparable to those observed with either treatment alone, suggesting a lack of additive or synergistic interaction. These findings demonstrate that QNPs exert a significant neuroprotective effect against reserpine-induced motor dysfunction and neurochemical disturbances, supporting their potential as a therapeutic strategy for Parkinsonian pathology.

Pharmacopeial methods are essential for pharmaceutical quality control, yet impurity profiling of levodopa/carbidopa fixed-dose combination tablets remains challenging because both actives are chemically labile and several structurally related impurities exhibit closely spaced retention behavior. During verification of the compendial procedure, a process-related impurity (1 R,3S)-6,7-Dihydroxy-1-methyl-1,2,3,4-tetrahydroisoquinoline-1,3-dicarboxylic acid (IP2) was found to co-elute with levodopa, compromising selective quantification and peak-purity assessment; moreover, small univariate adjustments (e.g., mobile-phase composition and pH) improved the levodopa/IP2 separation but created new critical overlaps among carbidopa, catechol, and levodopa related compound C, indicating limited robustness. To systematically resolve these deficiencies, a Design of Experiment (DoE) strategy was applied using a Box-Behnken response surface design to model and optimize three critical method parameters-ethanol content 11.5 - 31.5%, v/v, mobile-phase pH 2.20 - 2.50 and column temperature 26°C - 32°C with chromatographic resolutions between the most critical pairs as the primary responses; quadratic (second-order) regression models were generated and used with desirability-based numerical optimization to define operating conditions that maximize separation while maintaining suitable chromatographic performance. Under the optimized conditions mobile-phase pH, column (temperature 26°C, flow rate 0.9 mL/min, UV 280 nm, gradient runtime 75min), baseline separation of the critical impurity pairs was achieved, and system suitability confirmed adequate selectivity, including a resolution between levodopa related compound C and carbidopa in the System Suitability Test (SST) solution. Method robustness was further assessed using a Plackett-Burman design to identify parameters most sensitive to deliberate variation, supporting reliable performance under routine analytical conditions and across potential raw-material/formulation variability.

Copper-based nanozymes are increasingly used as artificial laccases, yet most rely on simple catechol ligands such as dopamine or gallic acid which provide limited control over metal coordination geometry and stability. In this work, we introduce methyldopa as a biomimetic bidentate ligand whose dual catechol-amine functionality closely reproduces the coordination environment of natural multicopper oxidases. This molecular design enables electronic tuning of the Cu(I)/Cu(II) redox cycle resulting in enhanced substrate affinity and exceptional thermal resilience. The prepared polymethyldopa-Cu nanoparticles (PMD-Cu NPs) exhibit robust laccase-like activity under near-physiological conditions catalyzing the oxidation of norepinephrine without additional oxidants. Beyond catalysis, the oxidation process provides an intrinsic colorimetric signal allowing simultaneous quantification and degradation of catecholamine pollutants as pyrogallol. Kinetic analysis (Km= 45 µM; Vmax= 5.0 µM/ min) demonstrates excellent catalytic performance and favorable substrate affinity compared with previously reported Cu-catechol nanozymes. By coupling strong Cu-ligand chelation with redox-active molecular design, methyldopa permits the construction of durable multifunctional nanozymes. This approach establishes a pathway toward tunable laccase mimics for biosensing, green chemistry, and environmental remediation. In addition, the sustainability and analytical efficiency of the developed platform were evaluated using the newly introduced EPPI metric alongside BAGI tool confirming its eco-friendly nature, practical applicability, and strong analytical performance.

Hypertensive disorders of pregnancy, particularly preeclampsia, are a leading cause of maternal and perinatal morbidity. While antihypertensive therapy is recommended, clinical uncertainty persists regarding the optimal agent to maximize maternal safety while minimizing adverse neonatal outcomes such as neonatal intensive care unit (NICU) admission. This review aimed to evaluate the comparative effectiveness and safety of pharmacological antihypertensive agents versus standard care or placebo in the management of hypertensive disorders of pregnancy through a network meta-analysis (NMA). A systematic review and frequentist random-effects NMA of randomized controlled trials (RCTs) was conducted. Major databases were searched for RCTs comparing antihypertensive agents (labetalol, nifedipine, methyldopa, hydralazine, prazosin) and controls. The primary neonatal outcome evaluated in this network was NICU admission. Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Twenty-five RCTs were included in the qualitative and quantitative synthesis. The network geometry was anchored by labetalol and nifedipine. In the NMA, no individual antihypertensive agent demonstrated a statistically significant reduction in the risk of NICU admission compared to labetalol. However, probabilistic ranking (P-scores) identified methyldopa (P-score = 0.859) and hydralazine (0.791) as the most favourable interventions for minimizing NICU admissions. Nifedipine showed a slightly elevated, though non-significant, risk profile compared to labetalol (RR 1.09, 95% CI 0.80-1.49). The placebo and standard care ranked lowest. The overall certainty of evidence ranged from moderate to very low due to imprecision and indirectness. Active pharmacological management of hypertension in pregnancy is superior to placebo or standard care. While labetalol and nifedipine remain mainstays for acute blood pressure control, methyldopa and hydralazine probabilistically rank higher for minimizing NICU admissions. These findings support individualized antihypertensive selection based on clinical acuity and maternal-fetal hemodynamics.

A 38-year-old Emirati man developed levodopa-responsive young-onset parkinsonism followed by electrophysiologically confirmed amyotrophic lateral sclerosis consistent with Brait-Fahn-Schwartz disease. Whole-genome sequencing identified a novel heterozygous POLG variant (c.2620T > A; p. Leu874Met). Motor fluctuations on oral therapy prompted escalation to continuous subcutaneous foslevodopa/foscarbidopa infusion, achieving near-complete motor normalization at twelve months. This is the first reported use of device-aided therapy in POLG-associated parkinsonian-ALS overlap.