Current Medicinal Chemistry - Volume 32, Issue 18, 2025

Metabolic syndrome is a multifactorial disorder and genetics, lifestyle, and aging play important roles in its prevalence. Nigella sativa has several pharmacological benefits, including anti-inflammatory, antitumor, anti-diabetic, antioxidant, and hypolipidemic effects. This meta-analysis of randomized controlled trials assesses the effect of N. sativa consumption on lipid profile and glycemic indices in patients with metabolic syndrome.

We systematically researched Cochrane Library, PubMed, Scopus, and Web of Science databases. The literature research identified 171 studies with duplication. Of those, 73 articles were screened for titles and abstracts, and 7 studies were finally selected for the meta-analysis. Because of the high degree of heterogeneity, we performed subgroup analyses based on the dose of N. sativa (<=500 mg/day or >500 mg/day).

The results revealed that N. sativa intake significantly decreased total cholesterol (SMD: −0.71; 95% CI, -1.44 to -0.38; p = 0.00), LDL-C (SMD: −1.06; 95% CI, -1.45 to -0.66; p = 0.00) and HDL-C (SMD: −0.31; 95% CI, 0.09 to 0.53; p = 0.01) concentrations. In addition, N. sativa significantly decreased FBS (SMD: −0.8; 95% CI, -1.21 to -0.39; p = 0.00) and HbA1c (SMD: −0.37; 95% CI, -0.66 to -0.09; p = 0.01) concentrations. No publication bias was observed, and sensitivity analysis showed stable results.

The current systematic review and meta-analysis indicates that N. sativa could improve lipid profile and glycemic index in patients with metabolic syndrome.

Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally.

The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. This was achieved by inhibiting lipid peroxidation and pro-inflammatory markers.

Rats were exposed to cognitive impairment produced by MA. The Morris water maze (MWM) is utilized to evaluate behavioral parameters. Biochemical tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1β (IL-1β), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets.

Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1β, CREB, TNF-α, BDNF, and Caspase 3 proteins expression. Furthermore, considerably restored level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol.

The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.

Hematological parameters are crucial factors in disease severity and chronic condition pathogenesis. We aimed to evaluate the hematological factors in different severity stages of COVID-19 at different time intervals.

Serum samples were collected from 470 patients (235 men and 235 women) with a confirmed RT-qPCR COVID-19 test exhibiting moderate, severe, and critical symptoms based on WHO criteria. Samples were collected at three-time intervals, including the first: the 1^st days of infection, 2^nd: the one month after, and 3^rd: the three months after disease onset. Total WBC, neutrophil, lymphocyte, monocyte, eosinophil, RBC counting, Hb, HCT, MCV, MCH, MCHC, hsCRP levels, G6PD deficiency, and hemoglobinopathies were determined in all patients.

Total WBC, neutrophil, lymphocyte, platelet, RBC counting, Hb, HCT, MCV, MCH, and hsCRP levels were significantly changed with different disease severity (p<0.0001). Also, there were significant differences between different time intervals for WBC and RBC parameters (p<0.0001) except for monocytes and eosinophils. At all time intervals, there are significant changes in levels of hematological and hsCRP based on gender. Moreover, a significant correlation was observed between disease severity, age, and BMI (p<0.0001).

Significant differences in hematological parameter and inflammatory parameter levels based on disease severity, time intervals, and gender revealed the importance of evaluating these factors in the management of infectious diseases, such as COVID-19, in patients during and post-disease times.

Microbial infections are mostly caused by Gram-positive as well as Gram-negative bacteria affecting millions of people worldwide. There is an urgent need to explore existing molecules or discover new chemical entities (NCEs) against bacterial infection.

The main objective of the current investigation is to explore recently US-FDA-approved drugs (2019-2023) against various targets of Gram-positive and Gram-negative bacteria using high-performance computational studies.

The current study aims to find out the potential drugs of recently US-FDA-approved drugs as repurposing candidates against bacterial infections.

The targets of Gram-positive and Gram-negative bacteria were identified using literature studies whereas ligands were selected from the FDA-approved drug lists of the last 5 years. Further, the drugs and targets were prepared through the LigPrep and Protein Preparation Wizard modules of Schrödinger (release 2023-1) respectively. The GlideDock and Desmond modules of Schrödinger were used for the molecular docking study and molecular dynamics simulation respectively.

A total of 202 drugs were found in the FDA lists which were approved in the last five years. Out of them, 77 drugs were selected for docking study based on their properties. A total of 21 drugs have shown energetically favored binding conformation of drugs in the active site of bacterial targets. The interaction of these drugs was studied in detail using molecular dynamics (MD) simulation. The MD simulation results have shown stable dynamic conformation of triclabendazole (anti-helminthic) with topoisomerase II of gram-negative bacteria whereas solriamfetol (for obstructive sleep apnea) has shown stable dynamic conformation in the active site of restriction endonuclease of Gram-positive bacteria.

The identified drugs can be repurposed against Gram-positive and Gram-negative bacterial infections. However, further experimental studies are required to confirm their antibacterial potential.

Among the various investigated drug carriers, metal-organic frameworks (MOFs) have recently gained attention due to their ability to adsorb different drugs and compatibility with various surface modification strategies. In this study, molecular dynamic simulation was conducted to assess the effect of chitosan on the loading of cyclophosphamide into MIL-100(Fe).

The simulations provided insights into atomic interactions by determining the coefficient of diffusion as mean squared displacement (MSD), resulting in values of 1.35 and 1.25 before and after chitosan coating, respectively. Experimental analysis of the chitosan-coated MIL-100(Fe) containing cyclophosphamide (MIL-100(Fe)/CS/CP) was performed using SEM, FTIR, BET, DLS, and powder X-ray diffraction. The drug loading and release processes were evaluated using UV-spectroscopy.

In vivo-in vitro studies were carried out to assess the performance of the system. The drug loading in chitosan-coated MIL-100(Fe) showed a significant increase compared to uncoated MIL-100(Fe), with payloads of 32% and 26.41%, respectively.

DLS analysis revealed that the presence of chitosan increased the particle size of MIL-100(Fe) from 381 to 463 nm and altered the zeta potential from 18 to -17 mV. The toxic impact of MIL-100(Fe)/CS/CP was evaluated on MCF-7 cells (human breast cancer cells) through in vivo experimental analysis. In vivo images and H&E analysis demonstrated the inhibitory effects of MIL-100(Fe)/CS/CP on tumor cells. Additionally, the drug loading of MIL-100(Fe) particles and MIL-100(Fe)/CS was simulated using the molecular dynamics software LAAMPS, providing further insights into the system's behavior and performance.