Iranian Journal of Pharmaceutical Research最新文献

Background: Streptococcus equi subsp. S. zooepidemicus is a notable producer of hyaluronic acid (HA), a natural polysaccharide widely utilized in the pharmaceutical, cosmetic, and food industries due to its unique properties.

Objectives: This study focuses on strain optimization and the purification of HA. The key goals include reducing hyaluronidase activity, which degrades HA, eliminating beta-hemolytic traits, and developing a purification process that significantly minimizes organic solvent consumption to lower costs and reduce environmental impact.

Methods: UV-induced physical mutagenesis and chemical mutagenesis utilizing nitrous acid and N-methyl-N'-nitro-N-nitrosoguanidine (NTG) were employed to generate mutant strains with diminished hyaluronidase activity and beta-hemolytic properties. Following strain optimization, an efficient downstream process was implemented, focusing on pre-treatment methods involving pH and temperature adjustments, followed by ultrafiltration and phenol acetate treatment.

Results: The selected mutant, designated as S. equi subsp. S. zooepidemicus K12, maintained stable mutation characteristics over 15 generations. The HA yield of the selected mutant showed an increase of 85.7%, rising from 0.42 g/L in the wild type to 0.78 g/L. According to gel permeation chromatography, the average molecular weight (Mw) of HA increased from 6.7 × 10⁴ Da to 1.2 × 10⁵ Da. Our purification strategy achieved a recovery rate of 72% with approximately 0.3% protein impurities, meeting European Pharmacopoeia (EP) standards. Additionally, organic solvent consumption was reduced by at least 25-fold compared to conventional methods.

Conclusions: The study presents an integrated approach to HA production, encompassing strain improvement and purification. It addresses key challenges in the manufacturing of streptococcal HA and contributes to the development of more efficient and environmentally friendly purification methods, ultimately resulting in high-purity HA.

Context: Uterine disorders are among the most prevalent gynecological problems in women. Persian Medicine (PM) has long provided herbal approaches for managing such conditions, based on temperament theory and humoral balance.

Objectives: This study aimed to identify medicinal plants used in PM for the treatment of uterine disorders and to assess their pharmacological evidence.

Methods: A literature review of classical PM texts, including Makhzan al-Adwiyyah and Taqwim al-Abdan, was conducted to extract herbs recommended for uterine ailments. Plant names, traditional indications, and temperament properties were documented. Modern pharmacological evidence for each plant was then retrieved from scientific databases (PubMed, Scopus, Web of Science).

Results: A total of 97 plant species belonging to 39 botanical families were identified. Most herbs exhibited hot and dry temperaments, aligning with the PM view that uterine disorders are linked to cold-moist imbalances. Common traditional indications included dysmenorrhea, endometrial inflammation, discharge, and cold uterus. In this study, the pharmacological findings for 10 key species, including Nigella sativa, Crocus sativus, and Vitex agnus-castus, were summarized.

Conclusions: Several PM herbs show promising potential for treating uterine disorders and align with modern pharmacological mechanisms. These findings provide a basis for further research and may support the development of evidence-based herbal therapies for women's reproductive health. Among the most frequently cited species, Foeniculum vulgare, V. agnus-castus, and N. sativa exhibit promising pharmacological activity, have shown potential uterotonic effects, and may support menstrual regulation, relieve uterine pain, and help modulate hormonal balance. The findings of this review may support the design of novel plant-based interventions in reproductive medicine, guided by both traditional knowledge and modern scientific evidence.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic inflammation, as well as metabolic and reproductive dysfunction. While insulin resistance affects many tissues, ovarian tissue exhibits insulin hypersensitivity, which promotes androgen excess and worsens PCOS symptoms. The kynurenine pathway (KP), a major route of tryptophan metabolism regulated by indoleamine 2,3-dioxygenase (IDO), is implicated in ovarian dysfunction in PCOS.

Objectives: To investigate the effects of IDO inhibition on ovarian morphology and insulin signaling in a PCOS rat model, evaluating its potential as a therapeutic approach compared to metformin.

Methods: Twenty-four female rats were randomly assigned to four groups: Control, PCOS, 1-methyltryptophan (1-MT, IDO inhibitor) (10 mg/kg), and metformin (100 mg/kg). The PCOS was induced by subcutaneous testosterone injections at 21 days of age. Outcomes measured included luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, ovarian weight, follicle and corpus luteum counts, granulosa and theca layer thickness, fasting blood glucose, and ovarian expression of insulin receptor substrate 1 (IRS-1) and phosphoinositide 3-kinase (PI3K).

Results: The results indicated that both treatments, 1-MT and metformin, significantly reduced the LH/FSH ratio, with metformin showing a more substantial effect. Additionally, 1-MT increased ovarian weight and the number of healthy follicles (HFs), unlike metformin. Both treatments increased the number of corpora lutea (CL), indicating restored ovulation. The IRS-1 expression decreased with both treatments, whereas PI3K levels remained unchanged.

Conclusions: The IDO inhibition by 1-MT improves ovarian function and hormonal balance in PCOS more effectively than metformin, likely by reducing inflammation and modulating insulin signaling. These findings support 1-MT as a promising therapeutic candidate for PCOS management and improving ovarian function. However, these results are from a short-term animal study, and further clinical trials are necessary to assess long-term efficacy and safety.

Background: Traditional Chinese medicines (TCMs) offer a comprehensive approach to managing malignant tumors.

Objectives: The present study aims to predict the high-frequency herbs, core components, and core targets for liver cancer treatment through data mining and network pharmacology.

Methods: The "traditional Chinese Medicine - active components - target - disease" network was established using Cytoscape to identify core components. A protein-protein interaction (PPI) network was constructed using the STRING database, and Cytoscape was used for network topological analysis to identify the core targets. Subsequently, molecular docking was performed using AutoDock Vina and PyMOL to calculate binding energies of core components with core targets. Furthermore, in vitro experiments explored quercetin's impact on liver cancer cell migration, apoptosis, and protein expression.

Results: A total of 50 high-frequency drugs were selected. Among these, Atractylodes macrocephala koidz, Astragalus membranaceus, Scutellaria barbata, and Cremastra appendiculata were high-frequency drugs for invigorating qi and heat-clearing in liver cancer treatment. There were 226 common targets of herbal medicine for liver cancer treatment. Based on the degree value, beta-sitosterol, kaempferol, stigmasterol, and luteolin potentially represented core components. Eight key targets, including JUN, MAPK1, RELA, TNF, ESR1, IL-6, TP53, and FOS, were screened out, which were involved in 417 entries and 159 pathways. Molecular docking verified a strong binding affinity of the key compounds to the core targets. In vitro experiments showed that quercetin induced apoptosis and inhibited migration activity of HepG2 cells in a dose-dependent manner by affecting the expression levels of p-c-Jun/c-Jun and c-Fos proteins.

Conclusions: This study provides a foundational basis for future clinical application of TCMs in liver cancer treatment.

Background: Chronic cerebral hypoperfusion (CCH) is a key contributor to vascular dementia (VaD) and Alzheimer's disease. Resveratrol (RSV), a polyphenol with potential neuroprotective properties, may mitigate CCH-induced neuronal damage, but its mechanisms remain unclear.

Objectives: This study investigated RSV's effects on memory enhancement through synaptogenesis and apoptosis inhibition in the hippocampus in a rat CCH model.

Methods: Forty male rats were randomly divided into four groups: Sham, 2-VO (bilateral carotid artery occlusion), 2-VO+RSV (2.5 mg/kg), and 2-VO+RSV (5 mg/kg). Initial group sizes (n = 10 each) were maintained by replacing deceased animals (2-VO: 7, 2-VO+RSV2.5: 4, 2-VO+RSV5: 6 deaths). The RSV was administered via intraperitoneal injection (ip) for 35 days post-surgery. Cognitive function was assessed using Morris water maze (MWM) and shuttle box tests. Hippocampal mRNA/protein levels of B-cell lymphoma 2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), Caspase-3, Ras homolog family member A (RhoA), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), calcium/calmodulin-dependent protein kinase II alpha (CaMKII-α), and N-methyl-D-aspartate receptor subunit 2B (NMDAR2B) were measured.

Results: The RSV (5 mg/kg) significantly improved spatial memory in the MWM. Also, RSV at doses of 2.5 and 5 mg/kg significantly increased the entrance latency to the dark compartment (P < 0.05 and P < 0.01 vs 2-VO, respectively). There was a downregulation of pro-apoptotic markers (Bax, Caspase-3) and Rho/ROCK gene expressions, and an upregulation of anti-apoptotic Bcl-2 gene expression and synaptic proteins (CaMKII-α, NMDAR2B) after RSV treatment. The RSV at 5 mg/kg significantly reduced the Bax/Bcl-2 ratio compared to the 2-VO group.

Conclusions: The RSV protects against CCH-induced neuronal damage by inhibiting apoptosis and enhancing synaptic plasticity. These findings highlight RSV's therapeutic potential for vascular cognitive impairment.

Context: Vancomycin is an important antibiotic with a glycopeptide structure, effective against gram-positive bacterial infections through the inhibition of bacterial cell wall biosynthesis. It is indicated for the treatment of serious complicated skin, bloodstream, lower respiratory tract, bone, and joint infections. Primarily administered intravascularly, vancomycin shows negligible oral bioavailability. This review discusses the mechanism of action and toxicity of vancomycin, along with resistance issues and the mechanisms involved.

Evidence acquisition: We covered updated literature regarding various delivery systems for vancomycin, including nanoparticles, nanofibers, microparticles, liposomes, and hydrogels. Their antimicrobial evaluations and significant results are presented, alongside summaries of attempts for vancomycin oral delivery. The main issues of vancomycin, such as poor physicochemical properties (high molecular mass and aqueous solubility), poor oral bioavailability, minimum inhibitory concentration (MIC) creep, emergence of resistance, and high tendency to accumulate in the kidneys, can be addressed using novel drug delivery systems.

Results and conclusions: We summarized a range of novel drug delivery systems that have been investigated for enhancing the efficacy of vancomycin. The data collected here could be used as a guide for fabricating proper carriers for vancomycin delivery and selecting appropriate antimicrobial tests. Further in-depth studies on the mechanisms by which nanoparticles overcome resistance and enhance drug efficacy may pave the way for designing more effective systems.

Background: Plant-based pain-relieving formulations have garnered attention in drug discovery, particularly those with a traditional background, often considered essential remedies for communities that rely on plant-based therapies for pain relief.

Objectives: This study aimed to develop and evaluate a semisolid nanoemulsion using Piper nigrum L. (black pepper) fruit essential oil, known for its analgesic properties, as the active ingredient.

Methods: A topical nanoemulsion was prepared under standard conditions using black pepper essential oil, emulsifiers, and excipients. Various combinations of Span 80 and Tween 80 were screened to achieve the desired hydrophilic-lipophilic balance (HLB) value. Among the several formulations prepared, a nanoemulsion sample was selected for detailed analytical and pharmaceutical evaluations. Gas chromatography with flame ionization detection (GC/FID) was used to identify and quantify major chemical constituents of the essential oil and the formulated nanoemulsion.

Results: An optimized combination of Span 80 and Tween 80, with an HLB of 11, contributed significantly to the physical stability of the formulations. A concentration of 2.7% P. nigrum essential oil in the nanoemulsion containing 3793.33 ± 222.75 µg/mL of caryophyllene, the major bioactive monoterpene, rendered a stable and acceptable nanoemulsion product. The nanoemulsion formulation ST42 was declared to have a viscosity of 1.8 MPa.s, ST mix (Span 80/Tween 80, 1.5:2.5), and a ratio of surfactant/essential oil (40:60), demonstrated optimal consistency and physical stability. The zeta potential (Z) of the optimized formulation ST42 was found to be close to neutral (-8.12 ± 2.0 mV), minimizing potential tissue irritation. The nanoemulsion was ultimately validated using a modified homogenization technique to improve droplet size, stability, and rheological characteristics.

Conclusions: The formulated black pepper nanoemulsion successfully passed key pharmaceutical quality tests, indicating its potential as a natural topical pain-relieving agent. Further in vivo studies and subsequent clinical trials may lead to the development of a plant-based product for managing neuropathic pain.

Background: Cancer is regarded as one of the most significant health concerns in the world. Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates and can lead to death. Cyclooxygenase (COX)-2 is responsible for the development of various cancers, including HCC. Therefore, the use of COX-2 inhibitors can help in the prevention and treatment of cancer.

Objectives: The present study aimed to synthesize and examine the effect of imidazolium [1,2-a] piperidinium (4cl-A) and benzo [d] imidazo [1,2-b] thiazolium (1-naphtyl-C) compounds as COX-2 inhibitors on the rat model of HCC.

Methods: Animals were randomly assigned to control and HCC induction groups. The study duration was 15 weeks. The HCC was induced using DEN (200 mg/kg, ip) at a single dose and 2-AAF (dietary, 0.02% w/w, for 2 weeks). After 15 weeks, the investigation focused on mitochondrial toxicity parameters. One-way and two-way ANOVA statistical tests were used to analyze the data.

Results: The results showed that 4cl-A and 1-naphtyl-C can reduce mitochondrial activity, increase the level of free radicals (ROS), collapse in mitochondrial membrane potential (MMP), cause swelling of mitochondria, and release cytochrome c from HCC mitochondria. While this effect was not observed in healthy mitochondria.

Conclusions: The results of the study indicate that these COX-2 inhibitors, along with selected drugs, can help in the treatment of HCC. However, more clinical studies should be conducted.

Background: At present, regarding the optimal potential for prevention and treatment of cancer, medicinal plants have received more attention than before. Stachys lavandulifolia is one of the 34 Stachys species found in various regions such as Iran. Although effective secondary metabolites have been identified in several species of the Stachys genus, research on the anticancer effects of extracts of S. lavandulifolia is limited.

Methods: In the present study, different extracts of S. lavandulifolia (n-hexane, chloroform, ethyl acetate, ethanol, hydroethanol, and water) were acquired, and three human cancer cell lines (H1299, MCF-7, and A2780) were used to analyze their anticancer effects.

Results: The chloroform and ethyl acetate extracts provided the highest toxicity against A2780 and were fractioned into A-E and F-J, respectively. Fractions C and F resulted in reducing the mitochondrial membrane potential (MMP), while fractions C, E, F, and I led to an increase in the activity of the caspase-3 enzyme. Fractions B, C, and I increased the reactive oxygen species (ROS) in the A2780 cells.

Conclusions: Considering the reduction in MMP and the increase in caspase-9 by fraction C, it can be said that apoptosis is induced by the intrinsic pathway.

Background: Rosa rugosa polysaccharides (RRP), a principal active component derived from R. rugosa Thunb., exert immunomodulatory effects. However, their therapeutic application is limited by rapid metabolism, short duration of action, and low bioavailability.

Objectives: To optimize the preparation process of Rosa rugosa polysaccharide liposomes (RRPL) and evaluate their immune cell activation in vitro.

Methods: The RRPL were prepared using the reverse-phase evaporation method, with encapsulation efficiency (EE) as the primary evaluation criterion. An orthogonal test was employed to optimize the preparation parameters. Various characteristics of RRPL were assessed, including morphology, particle size, Polydispersity Index (PDI), zeta potential, cumulative release rate in vitro, and stability. The immunological effects of RRPL were evaluated through cellular assays involving mouse spleen lymphocytes, peritoneal macrophages, and bone marrow-derived dendritic cells (BMDCs).

Results: The RRPL demonstrated an EE of approximately 81.96%, an average drug loading (DL) capacity of 13.86%, a particle size of 124.00 nm, a PDI of 0.23, and a zeta potential of -12.97 mV. The formulated RRPL exhibited high EE and DL capacity, alongside favorable slow-release properties and stability. These enhancements led to improved drug bioavailability and prolonged duration of action. Furthermore, RRPL significantly promoted the proliferation of spleen lymphocytes; enhanced the phagocytic activity of peritoneal macrophages; increased the secretion of interleukin (IL)-6, IL-1β, and interferon (IFN)-γ; activated immature BMDCs; and induced the maturation of BMDCs, resulting in increased production of IL-12p70 and tumor necrosis factor (TNF)-α.

Conclusions: This study successfully developed RRPL that markedly enhance immune cell activation compared with RRP. These findings provide a theoretical foundation for further exploration and development of these liposomal formulations.