Journal of Reports in Pharmaceutical Sciences
Volume:12 Issue: 1, Jan-Jun 2023

Peripheral neuropathy is a common side effect of chemotherapeutic agents. This study aimed to assess the impact of hydroalcoholic extract from Capparis spinosa fruit on mechanical allodynia and heat hyperalgesia induced by vincristine.

Vincristine (0.1 mg/kg/day, intraperitoneally) was used to induce peripheral neuropathy in rats for 2 weeks. The rats received treatment with the hydroalcoholic extract of Capparis spinosa fruit (100, 200, and 400 mg/kg, orally) or pregabalin (20 mg/kg, orally) for 2 weeks. Assessments of thermal and mechanical hyperalgesia were conducted using the hot plate, open field, footprint, grip strength, and von Frey hair tests. To investigate the roles of opioid and serotonergic pathways in anti-nociceptive and locomotor activities, naloxone (1 mg/kg) and cyproheptadine (5 mg/kg) were administered in conjunction with the extract.

Two weeks post vincristine administration, there was a significant decrease in thermal and mechanical nociceptive thresholds, muscle strength, and locomotor activity in rats compared to untreated groups. In all tests, pregabalin mitigated vincristine’s effects; notably, the Capparis spinosa extract at a dose of 400 mg/kg significantly reduced neuropathic behavioral changes compared to animals that received vincristine. The efficacy of the extract at the 400 mg/kg dose was diminished by naloxone in the von Frey filament test (P < 0.01), hot plate test (P < 0.05), and grip strength test (P < 0.001). Additionally, cyproheptadine reversed the extract’s effect in the grip strength (P < 0.0001) and von Frey filament tests (P < 0.01).

The findings suggest that the hydroalcoholic extract of Capparis spinosa fruit may counteract vincristine-induced neuropathic pain through opioidergic and serotonergic pathways. The extract’s beneficial effects are likely due to its flavonoid and phenolic compound content.

Solid lipid nanoparticles (SLNs) are colloidal carriers made up of lipids that are stabilized by surfactant molecules. The lipid matrix remains solid at body temperature. A significant challenge in the preparation of SLNs is determining the optimal concentration of surfactants due to their potential toxicity.

During the preparation of SLNs, micelle structures tend to form at high concentrations of surfactants. Since micelles exhibit different properties from SLNs, using the optimum concentration of surfactants leads to the preparation of a consistent formulation of SLNs. This was theoretically predicted in this study and then compared with experimental results.

In this study, amiodarone-loaded SLNs were produced via a hot homogenization process. The design of experiments was utilized to explore effective process parameters, as several factors influence the formulation characteristics. The concentration of surfactants was optimized using a Box-Behnken design. The results were compared with a theoretical equation developed in this study, which estimates the concentration of surfactants needed to cover the surface of the particles. Assessments included particle size and morphology, size distribution, drug loading percentage (DL%), and encapsulation efficiency (%).

The particle size of the optimum formulation was 74 ± 1.5 nm, with DL% and EE% being 14.81 ± 0.8% and 97.58 ± 2.5%, respectively. The formulation contained 2.3% Witepsol, 0.25% glyceryl monostearate (GMS), 0.5% amiodarone (AMI), 0.02% sodium lauryl sulfate (SLS), 0.05% poloxamer, and 0.17% lecithin. The total surface area of the particles was estimated according to the equation 6× (volume of the lipid phase)/ (diameter of particles), which can be applied to determine the concentration of surfactants required for preparing SLNs.

The results indicated that the theoretical equation was suitable for estimating the optimum concentration of surfactant in the aqueous phase to form SLNs and adequately cover the lipid surface. Mathematical estimations were comparable to the experimental results from the Box-Behnken design. Consequently, the formulation consisted of SLNs without any micellar structure, and the applied concentrations of surfactants effectively covered the surface of the particles.

Recently, there has been increased interest in medicinal plants for the discovery of new compounds to treat various disorders. A few studies have highlighted the antioxidant and anti-inflammatory effects of Lepidium draba.

This study explores the potential cardioprotective effects of L. draba against myocardial infarction (MI) induced by isoproterenol.

Isoproterenol (ISO) (100 mg/kg, injected subcutaneously for two consecutive days) was utilized to induce acute myocardial infarction in rats. The treated groups were administered hydroalcoholic extracts of L. draba intraperitoneally (ip) at doses of 50, 250, and 500 mg/kg for 2 consecutive days. Subsequently, the Electrocardiogram pattern, cardiodynamic parameters, cardiac remodeling, and lactate dehydrogenase levels were assessed.

The findings revealed that isoproterenol administration elevated the ST-segment and diminished the R-amplitude on the electrocardiogram, whereas treatment with L. draba extracts significantly ameliorated the ECG pattern. Isoproterenol injections lowered the mean arterial pressure (MAP), which was significantly increased by L. draba extract at all doses (P < 0.05). Furthermore, isoproterenol injections elevated lactate dehydrogenase (LDH) levels (P < 0.05) and cardiac fibrosis (P < 0.001), and treatment with the hydroalcoholic extract of L. draba significantly reduced both indices (P < 0.001 and P < 0.05, respectively).

This study is the first to demonstrate that L. draba administration protects myocardial tissue from isoproterenolinduced infarction. Consequently, this plant could be recommended as an adjunct treatment for patients with acute MI.

Withania somnifera (L.) Dunal, belonging to the Solanaceae family and commonly known as Ashwagandha, is a traditional Ayurvedic herb renowned for its adaptogenic properties. It plays a significant role in various classical Ayurvedic formulations and proprietary medicines. Traditionally, the roots of the plant are utilized over the aerial parts, such as leaves and stems. In recent years, a global increase in the use of Ashwagandha roots has been spurred by several modern pharmacological studies supporting its benefits.

This study examined different parts of the herb, including leaves, stems, roots, and seeds, using methods like phytochemical analysis, thin layer chromatography (TLC) analysis, high-performance thin layer chromatography (HPTLC) phytochemical profiling, UV-visible spectral analysis, and 1H nuclear magnetic resonance (NMR) profiling.

The findings indicated that phytosterols, triterpenoids, and alkaloids were predominantly found in the leaves and stems, with lower concentrations in the roots and seeds. Ethanol extracts were particularly rich in total flavonoids, whereas aqueous extracts contained higher levels of phenolic compounds. High-performance thin layer chromatography fingerprinting varied for each part of the herb, effectively separating pigment-based components such as chlorophyll at 366 nm in the aerial parts. The 1H NMR spectra showed distinct metabolite profiles for each part of the plant.

The analytical methods proposed in this study offer enhanced quality control and evaluation for the medicinal use of W. somnifera roots and its aerial components.

Echinochloa esculenta is the Indian Barnyard millet which is a grass type of species. This study focused on the evaluation of the antibacterial activity of Echinochloa esculenta-mediated zinc oxide nanoparticles (ZnONPs) against urinary tract infection (UTI) microbes, such as Escherichia coli ( E. coli), Enterobacter aerogenes, Pseudomonas aeruginosa, Staphylococcus aureus, and Proteus vulgaris.

The millet Echinochloa esculenta-mediated ZnONPs are synthesized using a green method. Synthesized ZnONPs are characterized by ultraviolet (UV), Fourier transform-infrared resonance spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX) to determine the functional groups, crystalline size, shape, and elemental composition of the synthesized NPs.

The UV and FTIR results of Echinochloa esculenta-mediated ZnONPs preliminarily confirmed the formation of ZnONPs. The XRD and SEM results also confirmed that the synthesized ZnONPs are well-crystalline in nature, and the average size was observed to be 23.38 nm with a spherical shape. Echinochloa esculenta-mediated ZnONPs contained 73.33% of zinc and 26.77% of oxygen, which was examined by EDX. Synthesized ZnONPs were tested against the five UTI pathogens, and they exhibited a greater zone of inhibitions than zinc acetate and plant extract. Especially against S. aureus, Echinochloa esculenta-mediated ZnONPs performed well with an inhibitory effect.

Therefore, this study had the potential value of developing new eco-friendly, low-cost, and less toxic nanomaterials that can be used as a bio-control for diseases.

The International Council on Harmonization issued quality by design (QbD) guidelines, including Q8 (R2) pharmaceutical development, Q9 quality risk management, and Q10 pharmaceutical quality system, to ensure the quality of pharmaceutical products. For continual and consistent improvement of the quality of pharmaceutical drug products, QbD tools, such as risk assessment, design of experiment, and control strategy, are used, which can solve the narrow areas in product development. Transdermal patch systems (TPS) are gaining attention among scientists and are one of the strong-growing drug delivery systems in the market as a result of numerous benefits, including lowering the dosing frequency, adverse effects and invasiveness, avoiding pre-systemic metabolism, and better patient efficiency and compatibility. Transdermal patch systems are a likable dosage form when compared to other dosage forms. However, several challenges are faced in TPS product development which has hindered enormous products concerning the market status of TPS in comparison to the oral dosage forms. The implementation of the QbD concept was much focused on oral dosage forms. Additionally, the lack of understanding of the development of TPS leads to failure and withdrawal from markets. Therefore, to understand the QbD concepts of TPS, an attempt has been made to review the QbD approach for the development of TPS from the identification of the Quality Target Product Profile to the arrival of design space, which might help the formulator to navigate the sticky areas, in the TPS development.

Brachyury has recently garnered attention as both a biomarker and a causative factor in chordoma development, making it a promising therapeutic vaccine.

Herein, we report a systematic review and meta-analysis to evaluate brachyury as a diagnostic biomarker and therapeutic molecular target in chordomas.

Scopus, PubMed/Medline, Cochrane Library databases, and Web of Science were searched up to July 18, 2024, without any restrictions. The Comprehensive Meta-Analysis version 3.0 software was used to calculate the event rate (ER) with a 95% confidence interval (CI). We utilized STRING to explore functional interactions among the studied genes.

Twenty-five studies related to the expression of brachyury and five related to the treatment vaccine of brachyury were included in this category. The ER of brachyury expression among chordoma patients was 92.2% (95% CI: 87.3% - 95.3%), with I² = 74.65%. Among the five studies related to treatment vaccines, there were three studies with Phase 1, one with Phase 2, and a case report.

The high expression suggests that brachyury serves as a reliable diagnostic marker for chordomas. The findings indicate potential therapeutic implications for targeting brachyury in chordoma treatment.

A newly emergent betacoronavirus, SARS-CoV-2, poses a tremendous global threat and causes severe acute respiratory syndrome coronavirus-2, a major pandemic that began worldwide in 2019. The trimeric spike glycoprotein (S) is located on the envelope of the virus and facilitates the fusion of viral and host cell membranes by interacting with a cellular receptor called angiotensin-converting enzyme 2 (ACE2). In the United Kingdom (UK), a variant of SARS-CoV-2 has been detected using sequencing technology. There has been a significant surge in the number of COVID-19 cases in South East England. These lineages are significantly more transmissible than previously circulating variants.

The aim of this study is to investigate the effects of UK SARS-CoV-2 spike mutations on its interactions with ACE2.

In this study, the structure of the UK spike protein with multiple mutations, including deletion 69 - 70, deletion 144, N501Y, A570D, T716I, D614G, P681H, S982A, and D1118H, was investigated. The research focuses on studying the impact of these mutations on spike function and its interactions with ACE2 through molecular dynamic simulation.

The results indicated that hydrophobic interactions, hydrogen bonds, and double/triple bonds are more prevalent in the mutated spike-ACE2 complex. Additionally, the UK spike-ACE2 complex maintained a consistent conformation throughout the simulation, experiencing minimal changes in structure. The mutant spike protein structure is less stable compared to the wild-type spike structure.

Multiple mutations, including deletion 69 - 70, deletion 144, N501Y, A570D, T716I, D614G, P681H, S982A, and D1118H in the spike protein of UK SARS-CoV-2, can affect its interaction with the ACE2 receptor and the transmissibility of this variant of SARS-CoV-2.

To investigate the anti-influenza mechanism of punicalagin and its inhibitory effects on influenza virus proteins, we conducted molecular docking studies targeting 11 viral proteins. Additionally, molecular dynamics simulations were performed for the protein with the lowest free energy and the minimum concentration required for binding in a simulated environment.

The molecular structure and data of punicalagin were obtained from the PubChem database and converted into a PDB file. FASTA sequences of viral proteins were retrieved from UniProt, and their PDB structures were predicted using the I-TASSER server. Molecular docking was performed using AutoDock 4.2 software, while molecular dynamics simulations were conducted with Gromacs 2022 software.

The PB1-F2 protein exhibited the best inhibitory performance, with a binding energy of -5.76 kcal/mol and the lowest inhibition constant (Ki). Docking of punicalagin to the PB1-F2 protein led to a significant decrease in the average total energy (TE), radius of gyration (Rg), and root mean square deviation (RMSD), as well as alterations in the secondary structure of the protein (P < 0.001). The most prominent secondary structural change was a reduction in coil structures and an increase in turn structures.

Punicalagin displayed a strong binding affinity for the PB1-F2 protein compared to other influenza viral proteins. Considering the role of PB1-F2 in exacerbating inflammation caused by influenza, punicalagin may mitigate inflammation in patients by modulating the activity of this protein.

Psoriasis is an intricate long-term inflammatory skin disease with a high outbreak rate and associated comorbidity. Literature reviews show the usefulness of various flavonoid (topical) formulations for treating/preventing psoriasis. However, both the low bioavailability and weak skin penetration of flavonoids significantly limit their practical application in the management of this autoimmune disease. A 36-year-old married woman presented with a ~26-year history of redness/erythema, thickness/induration, and scaling/desquamation of widespread psoriatic skin lesions, almost on the face/neck as well as upper/lower extremities. One month after the start of the treatment/intervention with the acylated-flavonoid, InflAQ, monotherapy, a remarkable improvement in the clinical appearance was achieved, specifically on the face and lower extremities. Two months later, erythema, scaling, and thickness were substantially reduced in places where the formulated InflAQ cream was applied. Using a modified form of quercetin (as a pro-drug/quercetin), we report the successful treatment of a female patient affected with Psoriasis vulgaris.

This study aimed to evaluate the effectiveness of thrombolysis with reteplase in patients with acute pulmonary embolism (PE) requiring thrombolytic treatment in the cardiac wards of Valiasr and Razi hospitals in Birjand, Iran. The study was conducted over a five-year period.

The study included patients with acute massive and sub-massive PE who received thrombolysis with reteplase from early 2016 to late 2020. Additionally, a one-year follow-up was conducted to monitor any complications.

A total of 28 patients participated in this study, with an average age of 54 ± 12 years. Findings showed that hypotension, chest pain, and hemoptysis resolved within 48 hours after reteplase administration. Reteplase also had a significant impact on improving hypoxemia (SPO2) and stabilizing vital signs, including heart rate (HR), respiratory rate (RR), and blood pressure (BP), as well as enhancing right ventricular (RV) function and reducing pulmonary artery pressure. The majority of patients (55%) had no deep vein involvement, and most did not report complications after discharge.

This study observed that reteplase was highly effective, leading to rapid clinical improvement without an increased risk of significant bleeding or mortality. Although limited by its retrospective nature, the study suggests that reteplase is a viable treatment option for PE.

Stimulation of N-Methyl-D-aspartate (NMDA) receptors with a neurotoxic dose of NMDA is commonly used to model certain characteristics of neurodegenerative disorders. A neurotoxic dose of NMDA injected into the CA1 region of the hippocampus causes excitotoxic damage and likely leads to memory impairment.

This study aimed to assess the effect of NMDA on passive avoidance learning and open-field tests in male rats, both with and without vitamin K (Vit K), to explore Vit K's potential neuroprotective properties.

Passive avoidance learning and open-field tests were conducted to assess recognition memory. In both tests, a retention session was held 24 hours post-training. N-Methyl-D-aspartate (20 µg/µL) was administered via cannula, and Vit K (10 mg/kg, s.c.) was given daily for 30 days into the CA1 region.

N-Methyl-D-aspartate administration reduced step-through latency (STL) and increased time spent in the dark compartment (TDC) during retention sessions. It also decreased locomotor activity and rearing behavior in open-field tests. In contrast, Vit K increased STL and decreased TDC in NMDA-treated rats, with observed improvements in locomotor activity and rearing behavior.

N-Methyl-D-aspartate administration in the CA1 region induced memory deficits in passive avoidance and open-field tests. The findings suggest that Vit K may exert neuroprotective effects against NMDA-induced excitotoxic neuronal damage, potentially improving memory impairments.

Malaria, a parasitic disease caused by a single-celled parasite called Plasmodium, poses a significant global health burden, especially in tropical regions such as Africa. The impact of malaria on human health is well-documented; however, its effects on the male reproductive system and the impact of herbal extracts remain underexplored.

This study aims to investigate Azadirachta indica's toxicity and its antimalarial potency's influence on testicular function and expression of proliferating cells nuclear antigen (PCNA).

The antimalarial activity of Azadirachta indica was determined using standard procedures. Thirty male mice were used and grouped into six. Group 1 (normal control), group 2 (P. berghei infected only - negative control), group 3 (Plasmodium berghei infected + lonart - standard drug), group 4 (P. berghei infected + 100 mg/kg BWT crude ethanol extract), group 5 (P. berghei infected + 200 mg/kg BWT crude ethanol extract), group 6 (P. berghei infected + 400 mg/kg BWT crude ethanol extract). Administration of A. indica leaf extract to infected mice for four consecutive days demonstrated promising results.

The extract significantly suppressed parasite multiplication, ameliorated testicular damage, and improved sperm quality. The non-toxic extract also reduced oxidative stress in the testes, suggesting its potential effectiveness as phytotherapy against malaria-induced male reproductive impairments.

The beneficial effects of A. indica emphasize its potential as a natural remedy for malaria-induced reproductive complications, offering a new avenue for therapeutic intervention in malaria-endemic regions. This study contributes to our knowledge of the intricate relationship between malaria and male reproductive health and provides valuable insights for future research and clinical applications.

Lipopolysaccharide (LPS) has been shown to cause depression by activating microglia and inducing pro-inflammatory factors in the brain. Citrus medica (CM) is a plant with known therapeutic effects. In this study, depression was induced in mice using intraperitoneal (IP) LPS (1 mg/kg). Two days later, behavioral tests were conducted. Mice were divided into nine groups of seven, including the control group, LPS group, CM extract groups (at different doses), L-arginine (L-Arg, alone and with an effective 1.dose of CM extract), aminoguanidine (AG, with an ineffective dose of CM extract), L-NAME (with an ineffective dose of CM extract), and fluoxetine 30 minutes before LPS. In the behavioral tests, the duration of immobility in mice treated with CM extract was reduced compared to the control and LPS groups. Treatment with L-Arg increased the duration of immobility, which was reversed by CM extract. The concurrent administration of L-NAME and AG with CM extract demonstrated synergistic antidepressant effects.

Newborns in the neonatal intensive care unit (NICU) are exposed to numerous medications during theirhospital stay. The clinical variability of neonates makes them particularly vulnerable to drug-related problems (DRPs), leadingto potential treatment inefficacy.

This study aimed to investigate the prevalence of DRPs and identify associated risk factors in neonates with sepsisin the NICU.

This prospective observational research was conducted at a children's medical center in Iran from December 1, 2021,to March 1, 2022. Data were collected through daily physician orders and nursing reports, with DRPs classified according toCipolle's standards. Logistic regression was utilized to determine risk factors for DRPs, with significance set at P < 0.05.

A total of 272 neonates with sepsis were included in the study, with mean birth weight andgestational age of 1781 ± 912 g and 35.4 ± 1.3 weeks, respectively. DRPs were observed in 57.5% of neonates (95% CI: 55.8 - 63.8%), withineffective drugs (24.1%) and dosage issues (19.7% too low, 22.6% too high) being the primary causes. Antimicrobials accounted forthe majority of DRPs (61.2%), with Gentamicin (21.5%) and Amikacin (17.3%) being the most commonly involved medications. Riskfactors for DRPs included feeding intolerance and vomiting, with ineffective drug selection and inappropriate dosing impactingtreatment efficacy.

Cognitive impairment has been identified in all stages and affects all subtypes of multiple sclerosis (MS) (40 - 65% of people with clinically definite MS). A defined therapeutic strategy has not yet been determined.

This study aimed to assess the efficacy of levetiracetam (LEV) to improve cognitive impairments in patients with relapsing-remitting MS (RRMS).

A Pilot randomized; double-blinded, placebo-controlled clinical trial was conducted. The patients with a definite diagnosis of RRMS treated with first-line drugs. They were assigned into two groups; LEV and the placebo for four months. The primary outcome was the changes in cognitive domains based on the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) compared to baseline. The MACFIMS was accomplished by seven tests: California verbal learning test-II (CVLT-II), paced auditory serial addition test (PASAT), symbol digit modalities testing (SDMT), brief visuospatial memory testrevised (BVMT-R), delis-Kaplan executive function system (D-KEFS), controlled oral word association test (COWAT), and judgment of line orientation (JLO).

A total of 32 patients entered the study and 28 patients completed the trial. The change in JLO score in the LEV group was significantly greater than in the placebo group (P-value = 0.03). After intervention in the LEV group, the SDMT and JLO scores were significantly higher than the baseline scores.

This is the study to evaluate the effects of LEV on cognitive disorders in patients with MS. Levetiracetam was significantly effective in improving the JLO and SDMT scores in patients with RRMS compared to the placebo group.