Iranian Journal of Pharmaceutical Research最新文献

Osbeckia opipara, a traditional Miao medicine, is commonly used by the renowned national-level Chinese Traditional Medicine practitioner Zhengshi Wu for the treatment of diarrhea due to its strong antioxidative, anti-inflammatory, and antidiarrheal effects. This study aimed to establish a high-performance liquid chromatography (HPLC) fingerprint for O. opipara to provide new evidence and technical means for the scientific evaluation and effective quality control of O. opipara. The procedure involved isolation with a Nano ChromCore C18 column (250 mm × 4.6 mm, 5 μm), using a gradient elution of 0.1% formic acid in water and 0.1% formic acid in acetonitrile as the mobile phase, with a flow rate of 1.0 mL/min, a column temperature of 30°C, an injection volume of 10 μL, and detection at a wavelength of 254 nm. Under these chromatographic conditions, fingerprint analysis was conducted on 11 batches of O. opipara collected from different origins. The National Pharmacopoeia Committee developed the 'Chromatographic Fingerprint Similarity Evaluation System' (2004A version) for automated comparison, similarity computation, and analysis of chromatographic data. The results revealed 13 common peaks across the 11 batches of O. opipara samples, with a similarity to the automatically generated reference spectrum exceeding 0.9. SPSS 26.0 software was used to conduct cluster analysis on the peak areas of the 13 common peaks. The observations indicated that the reference spectrum generated from the 11 batches could serve as the standard fingerprint profile for O. opipara, providing sufficient characteristic information extraction.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, including deficits in memory and other cognitive functions. Oxidative stress and free radical damage play significant roles in its pathogenesis. This study aimed to investigate the potential anti-inflammatory and neuroprotective effects of Pistacia atlantica gum (administered at doses of 50 and 100 mg/kg for 14 days) in a rat model of AD induced by aluminum chloride (AlCl₃). Behavioral changes were assessed using open field, passive avoidance, and elevated plus maze tests. Additionally, nitrite levels, nuclear factor-kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and immunostaining were evaluated. Administration of P. atlantica gum significantly increased step-through latency in the passive avoidance test (P < 0.01 and P < 0.001), enhanced mobility in the open field test (P < 0.01 and P < 0.001), and reduced anxiety-like behaviors in the elevated plus maze (P < 0.001) compared to the AlCl₃ group. Treatment with the gum partially normalized the elevated levels of NF-κB and the decreased levels of BDNF caused by AlCl₃ exposure. Our findings suggest that P. atlantica gum administration may alleviate oxidative stress, neuroinflammation, and cognitive impairment in AD rats.

Background: Insulin resistance is an important pathological hallmark of Parkinson's disease (PD). Proinflammatory cytokines during neuroinflammation decrease insulin sensitivity by suppressing insulin signaling elements. Toll-like receptor 4 (TLR4), the main receptor involved in neuroinflammation, is also associated with the pathogenesis of PD.

Objectives: The present study evaluated the effect of insulin, an insulin receptor antagonist, and a TLR4 inhibitor on behavioral deficits and insulin resistance induced by 6-hydroxydopamine (6-OHDA).

Methods: Male Wistar rats were divided into nine groups: (1) sham (normal saline [NS] in the medial forebrain bundle [MFB]); (2) 6-OHDA (20 µg in the MFB); (3) 6-OHDA + NS; (4) 6-OHDA + dimethyl sulfoxide (DMSO); (5) 6-OHDA + insulin (2.5 IU/day, intracerebroventricular ([ICV]); (6) 6-OHDA + insulin (5 IU/day, intranasal [IN]); (7) 6-OHDA + insulin receptor antagonist (S961; 6.5 nM/kg, ICV); (8) 6-OHDA + TLR4 inhibitor (TAK242; 0.01 µg/rat, ICV); (9) 6-OHDA + insulin + TLR4 inhibitor. All treatments were administered for seven consecutive days. Motor performance was evaluated using apomorphine-induced rotation and cylinder tests. Gene expression and protein levels of α-synuclein, TLR4, insulin receptor substrate (IRS) 1, IRS2, and glycogen synthase kinase 3β (GSK3β) were measured by real-time PCR and western blotting, respectively, in the striatum.

Results: Insulin, alone and with TAK242, improved motor deficits induced by 6-OHDA. Administration of the insulin receptor antagonist had no effect on motor deficits. The increased expression of α-synuclein and TLR4 following 6-OHDA was attenuated by insulin and TAK242. GSK3β levels, both mRNA and protein, were significantly increased by 6-OHDA and attenuated with insulin and TAK242.

Conclusions: The findings suggest that 6-OHDA induces neurodegeneration via activation of TLR4 and GSK3β, indicating insulin resistance, and that insulin can improve these impairments. Moreover, TLR4 inhibition prevents insulin signaling dysfunction and improves behavioral and molecular impairments, highlighting the critical role of TLR4 in the development of insulin resistance in PD pathology.

Background: The incidence of colorectal cancer is increasing globally. Daunorubicin (DNR), an anthracycline antibiotic, is effective against various cancers. The PI3K/AKT/mTOR signaling pathway is crucial in regulating cell growth and cancer growth.

Objectives: This study aims to evaluate the effects of liposomal daunorubicin (Lip-DNR) on cell proliferation and cell death induction in HCT116 cells compared to free daunorubicin.

Methods: Lip-DNR was synthesized, and its shape and size were analyzed using FE-SEM imaging. HCT116 cells were treated with Lip-DNR concentrations of 0 (control), 0.125, 0.25, 0.5, 1, and 2 μm for 48 hours to determine the IC50. The effects of free (0.5 μm) and liposomal DNR (IC50 of 0.43 μm) on PI3K mRNA levels were assessed using real-time PCR. The cell cycle was analyzed by flow cytometry.

Results: FE-SEM imaging showed that the liposomes are spherical and range from 50 - 100 nm in size. Lip-DNR induced cell death in HCT116 cells in a dose-dependent manner, with 0.5 μm Lip-DNR causing more cell death than an equivalent concentration of free DNR. Analysis of PI3K gene expression showed that DNR decreases PI3K gene transcription in HCT116 cells, with Lip-DNR having a more substantial effect than the free form. Both forms reduced the proportion of G2/M phase cells, but Lip-DNR was more effective at inhibiting cell proliferation in HCT116 cells.

Conclusions: DNR inhibits the proliferation of HCT116 cells by downregulating PI3K gene expression and enhancing cell death, with the liposomal form demonstrating stronger effects than the free form.

Background: Providing data on the superior efficacy of vancomycin administered based on the area under the curve over 24 hours to the minimum inhibitory concentration of vancomycin (AUC₂₄/MIC) is crucial. However, data on dosing and monitoring of vancomycin pharmacokinetics in the pediatric population are limited. Previous findings have showed that intermittent infusion of vancomycin (IIV) may not achieve the desired levels, continous infusions of vancomycin (CIV) reach the desired serum concentration faster than IIV and are associated with reduced nephrotoxicity.

Objectives: This study aimed to compare the serum concentrations, AUC₂₄, clinical variables, and adverse effects of two vancomycin administration methods in the pediatric population.

Methods: This study was a double-blind, randomized, controlled clinical trial conducted at a tertiary children's teaching hospital. Inclusion criteria were age between 2 months and 15 years and weight less than 67 kilograms, with exclusion criteria including renal impairment. Participants were divided into CIV and IIV groups following distinct administration protocols. Demographic, clinical, and laboratory data, including vancomycin serum concentrations, were compiled. Assessments included pediatric mortality risk, pediatric sequential organ failure assessment, and regular temperature monitoring. Pharmacokinetic analysis was conducted using Monolix software 2023R1. Primary endpoints were vancomycin serum levels and AUC₂₄ between cohorts on day three, with nephrotoxicity and additional adverse drug responses evaluated.

Results: Sixty-eight patients in the pediatric intensive care unit (PICU) were allocated to either CIV (33) or IIV (35) for vancomycin treatment. In the CIV group, 82% of patients achieved an AUC₂₄ ≥ 400 mg.h/L, compared to 23% in the IIV group. Continuous infusions of vancomycin demonstrated a greater AUC₂₄ (587.7 ± 184.4 mg.h/L vs. 361.9 ± 113.2 mg.h/L, P < 0.05) compared to IIV. Two cases of nephrotoxicity were reported, one in each group, with mortality and adverse events being comparable between the two groups.

Conclusions: This study demonstrated that continuous vancomycin infusion has a higher success rate in safely achieving therapeutic vancomycin levels in PICU patients compared to intermittent vancomycin infusion.

Background: Doxorubicin (DOX) is used in the treatment of various cancers and has good effectiveness. However, its therapeutic use is limited due to its effects on various organs and healthy cells. Doxorubicin can affect the kidneys and cause toxicity. Evidence shows that DOX induces nephrotoxicity through oxidative stress.

Objectives: In this research, we examined the effect of mitochondrial transplantation on improving mitochondrial and cellular toxicity caused by DOX on renal proximal tubular cells (RPTCs).

Methods: The research measured 7 toxicity parameters, including cell lysis, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) decline, GSH and GSSG content, lipid peroxidation (LPO), adenosine triphosphate (ATP) content, and Caspase-3 activity (the final mediator of apoptosis). Active fresh mitochondria were prepared from Wistar rat kidney.

Results: The findings indicated that DOX caused cytotoxicity in RPTCs. Additionally, DOX induced oxidative stress by increasing the level of reactive oxygen species, reducing glutathione content, and elevating lipid peroxidation. Moreover, it led to damage to the mitochondrial membrane, increased caspase-3 activity, and decreased ATP content. Mitochondrial transplantation, as a new therapeutic approach, reduced oxidative stress, mitochondrial membrane damage, and apoptosis caused by DOX in RPTCs. Furthermore, this therapeutic approach increased the ATP content in RPTCs.

Conclusions: Our study suggests that this therapeutic approach could be helpful in the treatment of drug-induced nephrotoxicity.

Background: The abnormal expression of microRNA (miRNA) influences RNA transcription and protein translation, leading to tumor progression and metastasis. Today, reliably identifying aberrant miRNA expression remains challenging, especially when employing quick, simple, and portable detection methods.

Objectives: This study aimed to diagnose and detect the miR-21 biomarker with high sensitivity and specificity.

Methods: Our detection approach involves immobilizing ROX dye-labeled single-stranded DNA probes (ROX-labeled ssDNA) onto MWCNTs to detect target miRNA-21. Initially, adsorbing ROX-labeled ssDNA onto MWCNTs causes fluorescence quenching of ROX. Subsequently, introducing its complementary DNA (cDNA) forms double-stranded DNA (dsDNA), which results in the desorption and release from MWCNTs, thus restoring ROX fluorescence.

Results: The study examined changes in fluorescence intensities before and after hybridization with miRNA-21. The fluorescence emission intensities responded linearly to increases in miR-21 concentration from 10^-9 to 3.2 × 10^-6 M. The developed fluorescence sensor exhibited a detection limit of 1.12 × 10^-9 M.

Conclusions: This work demonstrates that using a nano-biosensor based on carbon nanotubes offers a highly sensitive method for the early detection of colorectal cancer (CRC), supplementing existing techniques.

Background: This study aimed to develop a microemulsion (ME)-based skin delivery platform containing sildenafil citrate (SC)-ME and evaluate its in vitro skin permeability.

Methods: Accurate MEs were prepared using pseudo-ternary phase diagrams and a full factorial design with three variables at two levels. After the design phase, suitable ratios of oil, water, and a mixture of surfactant (S) and cosurfactant (CS) were selected to prepare various SC-ME formulations. These SC-MEs were analyzed for stability, droplet size, in vitro SC release, skin permeability, and viscosity properties.

Results: The droplet size of the ME samples ranged from 6.24 to 32.65 nm, with viscosities between 114 to 239 cps. Release profiles indicated that 26 to 60% of SC was released from the different SC-MEs within 24 hours. All ME formulations significantly enhanced the permeability coefficient (P) through rat skin. Specifically, the flux (J_ss) in SC-ME7 increased by approximately 117 times (J_ss = 0.0235 mg/cm².h) compared to the control sample (0.0002 mg/cm².h).

Conclusions: The study concluded that the proportions of the water or oil phase and the S/CS mixture in the MEs significantly influenced the physicochemical characteristics and permeation parameters. The selected MEs improved both the permeability coefficient and the rate of permeation through rat skin. The enhanced drug delivery through and into deep skin layers is a key attribute of an ideal dermal ME. These findings suggest that MEs could serve as effective transdermal delivery systems for SC and similar drugs. However, in vivo assays and clinical research are needed to confirm the therapeutic efficacy of MEs.

Background: Crocin is a water-soluble carotenoid compound present in saffron (Crocus sativus L.), known for its wide range of pharmacological activities, including cardioprotective, hepatoprotective, anti-tumorigenic, anti-atherosclerosis, and anti-inflammatory effects.

Objectives: The instability of crocin, its low miscibility with oils, and poor bioavailability pose challenges for its pharmaceutical applications. This study aimed to design and prepare a crocin-phospholipid complex (CPC) and assess its physicochemical properties.

Methods: The study investigated the formation of the complex and its binding affinity through molecular docking. Molecular dynamics (MD) simulations were conducted to find the optimal molar ratio of crocin to phospholipid for the complex's preparation. The CPC was produced using the solvent evaporation method. Techniques such as X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FE-SEM), nuclear magnetic resonance (NMR), and solubility studies were utilized to characterize and confirm the formation of CPC. Additionally, the in vitro antioxidant activity of crocin and CPC was evaluated.

Results: Molecular dynamic simulations explored molar ratios of 1: 1, 1: 1.5, and 1: 2 for crocin to phospholipid. The ratio of 1: 2 was found to be the most stable, exhibiting the highest probability of hydrogen bond formation. Molecular docking, FTIR, and NMR studies indicated hydrogen bond interactions between crocin and phospholipid, confirming CPC's formation. XRD and FE-SEM analyses showed a decrease in crocin's crystallinity within the phospholipid complex. Furthermore, the solubility of crocin in n-octanol was enhanced post-complexation, indicating an increase in crocin's lipophilic nature.

Conclusions: Phospholipid complexation emerges as a promising technique for enhancing the physicochemical characteristics of crocin.

Background: Polycystic ovary syndrome (PCOS) is the most common gynecological endocrine disorder.

Objectives: This study evaluated the therapeutic effects of Pimpinella anisum L. (P. anisum) fruit on pro-inflammatory cytokines, oxidative stress markers, and ovarian tissue structure in a rat model of PCOS.

Methods: After inducing PCOS, female Wistar rats were randomly divided into control and PCOS groups. They orally received daily doses of normal saline or hydro-alcoholic extract of P. anisum at two doses (200 and 400 mg/kg) for 21 days. At the end of the treatment period, ovarian and liver tissues were collected to measure lipid peroxidation, antioxidant status, TNF-α, IL-6 mRNA expression, and its content. Additionally, histopathological examinations of the ovarian tissue were conducted.

Results: Our findings revealed a dose-dependent change in the biochemical and histopathological parameters. Treatment with P. anisum resulted in a significant decrease in TNF-α and IL-6 mRNA expression levels and their content in the ovarian and liver tissues. It also reduced MDA levels while increasing SOD and GPx activity in both ovarian and liver tissues of PCOS rats. Furthermore, the number of follicular cysts in the PCOS rat model was significantly reduced.

Conclusions: The beneficial effects of P. anisum in PCOS rats are partly attributed to the inhibition of inflammatory and oxidative stress markers in ovarian tissue. These findings suggest that P. anisum could be a potential candidate for the treatment of PCOS disorders.