Iranian Journal of Pharmaceutical Research最新文献

[This corrects the article DOI: 10.5812/ijpr-166426.].

Background: The human microbiota plays a crucial role in maintaining host health and is involved in various illnesses, including cancer. The intestinal microbiota has been identified as a factor in the development of colorectal carcinoma and breast cancer (BC).

Objectives: This study investigated the anticancer properties of bacteriocins produced by Lactobacillus acidophilus, specifically their interaction with receptor tyrosine kinase-like orphan receptor 1 (ROR-1), a protein involved in aggressive BC subtypes.

Methods: Employing sophisticated computational methodologies, encompassing molecular docking and molecular dynamics (MD) simulations, this research elucidated the dynamic interactions and binding strengths of four distinct bacteriocins - Acidocin A, Acidocin B, Acidocin 8912, and Acidocin J1132β - with the ROR-1 receptor. This observation was substantiated by consistent hydrogen bond formation and low root mean square deviation (RMSD) values throughout the simulation period. Furthermore, the biological activity of crude acidocins was evaluated on the ROR-1-Src signaling axis in Michigan Cancer Foundation-7 (MCF-7) and MDA-MB-231 cell lines utilizing Western blot analysis.

Results: The findings of this research demonstrate that Acidocin A exhibits promise as a prospective therapeutic intervention directed at ROR-1 in BC. Furthermore, the synergistic application of molecular docking, MD simulations, and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy calculations yielded a thorough elucidation of the underlying interaction mechanisms. The assessment of protein expression levels indicated a significant downregulation of the ROR-1-Src signaling pathway following treatment with Acidocins.

Conclusions: This research highlights the potential of bacteriocins in cancer treatment and adds to evidence linking the microbiota to cancer, establishing new pathways for anticancer therapies from microbial sources.

Background: Leuenbergeria bleo, a medicinal plant with traditional therapeutic uses, has attracted interest for its antidiabetic potential.

Objectives: This study evaluated the antihyperglycemic effects of its leaf extracts in an alloxan-induced diabetic rat model.

Methods: The leaves of L. bleo were sequentially extracted using petroleum ether, chloroform, and methanol. Phytochemical screening was conducted to identify bioactive compounds such as phytosterols, alkaloids, tannins, and flavonoids. Thirty healthy Albino Wistar rats were divided into five groups. Diabetes was induced in four groups via intraperitoneal injection of alloxan monohydrate (140 mg/kg). The diabetic rats were treated with either chloroform or methanol extracts of L. bleo (500 mg/kg/day) for five days, with metformin (100 mg/kg/day) serving as the standard reference treatment. Blood glucose levels were monitored daily, and body weight was recorded on days 1, 3, and 5.

Results: Methanol extract significantly reduced blood glucose levels by 12.23% by day 5, compared to a 6.35% reduction with chloroform extract. Additionally, the methanol extracts mitigated weight loss, resulting in an 8.07% increase in body weight, while the diabetic control group experienced a 26.72% decrease. The effects of the methanol extract were comparable to metformin, though slightly less potent. Leuenbergeria bleo exhibits modest antihyperglycemic potential, particularly in its methanol extract, which also stabilizes body weight in diabetic rats.

Conclusions: The presence of flavonoids and alkaloids likely contributes to these effects. Further research is warranted to elucidate the exact mechanisms and explore L. bleo's potential as a natural alternative therapy for diabetes management.

Context: This review explores the antifungal potential of Allium species, emphasizing pure compounds identified through phytochemical studies. It also analyzes the mechanisms and efficacy of Allium-derived antifungal agents within pharmaceutical, agricultural, and food science applications.

Objectives: To assess the antifungal properties of major Allium species and their bioactive compounds, and to evaluate their mechanisms of action and effectiveness across pharmaceutical treatments, agricultural pathogen control, and food preservation.

Data sources: A comprehensive literature search was conducted using major scientific databases, including Web of Science, PubMed, ScienceDirect, Scopus, and Google Scholar.

Study selection: Studies reporting antifungal activities of major Allium species and their isolated compounds were selected based on PRISMA guidelines.

Data extraction: Data were extracted from recent research focusing on the antifungal effects, mechanisms of action, and minimum inhibitory concentrations of sulfur compounds and saponins derived from Allium species.

Results: Sulfur-containing compounds such as allicin and ajoene were found to disrupt fungal cell metabolism, destabilize cellular structures, and induce oxidative stress. These compounds showed strong activity against pathogens including Candida albicans and Aspergillus fumigatus. Saponins were also identified as key antifungal agents, with spirostane and spirostanol saponins from species like A. ampeloprasum and A. porrum demonstrating activity against C. albicans, A. niger, and Fusarium culmorum. Additional saponins - such as Fistoloside C, Minutoside B, and Ceposide variants - exhibited promising antifungal potential, particularly in combination therapies. Reported minimum inhibitory concentrations ranged from 0.15 µg/mL for sulfur compounds to 3.1-800+ µg/mL for saponins.

Conclusions: Saponins from Allium species represent promising adjuncts for overcoming antifungal drug resistance and may expand treatment options beyond traditional sulfur-derived compounds. These bioactive molecules also show potential for agricultural use against soil-borne pathogens like F. oxysporum, as well as food preservation applications against spoilage fungi such as Penicillium italicum and A. niger. Overall, Allium species constitute a valuable natural source of antifungal agents with broad pharmaceutical and agricultural relevance.

Background: Pulmonary fibrosis (PF) is characterized by dysregulated signaling, with the Wnt/β-catenin pathway playing a critical role. Pin1, a peptidyl-prolyl isomerase, is implicated in post-translational modifications and cellular signaling.

Objectives: This study explores the expression, localization, and functional role of Pin1 in regulating Wnt/β-catenin signaling in human lung fibroblasts (MRC-5 cells). These cells, derived from normal lung tissue, are commonly used to model fibrotic processes due to their ability to mimic fibroblast behavior in PF. Importantly, we report the first demonstration of Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1)-mediated Pin1 activation in the context of PF. Notably, we demonstrate that EBV-LMP1 activates Pin1 and amplifies Wnt/β-catenin signaling in fibroblasts.

Methods: We employed a combination of Pin1 overexpression and siRNA-mediated knockdown in MRC-5 cells to assess pathway modulation. Subcellular localization analysis was performed, and pathway output was evaluated by quantifying β-catenin, cyclin D1, and Axin2 via Western blotting. Co-immunoprecipitation (Co-IP) was used to examine the Pin1-β-catenin interaction. To examine viral contributions, LMP1 overexpression was carried out, and pharmacological inhibition of Pin1 was achieved using Juglone and PiB.

Results: Pin1 expression was significantly higher in MRC-5 cells compared to alveolar epithelial cells, with a 2.5-fold increase in protein levels (P < 0.05). Pin1 was localized to both the cytoplasm and nucleus. Overexpression of Pin1 led to an approximately two-fold increase in β-catenin (192%), cyclin D1 (178%), and Axin2 (165%) expression compared to controls (P < 0.01), while knockdown reduced their levels by 60%, 55%, and 63%, respectively (P < 0.01). The LMP1 overexpression increased Pin1 by 1.8-fold, strengthened its interaction with β-catenin, and amplified Wnt/β-catenin signaling. Treatment with Wnt3a further enhanced β-catenin expression by 2.4-fold, while XAV939 reduced it by 66% (P < 0.01). Pharmacological inhibition of Pin1 using Juglone and PiB significantly suppressed pathway activation, including LMP1-induced enhancement, with reductions in β-catenin levels by 68% and 72%, respectively (P < 0.01).

Conclusions: Pin1 is a critical regulator of the Wnt/β-catenin pathway in PF, integrating signals from viral and cellular modulators. This study provides novel evidence of EBV-LMP1's role in activating Pin1 in lung fibroblasts, reinforcing its value as a therapeutic target. Pin1 inhibitors effectively downregulate this signaling cascade, even under hyperactive conditions, highlighting their therapeutic potential for PF treatment. While Pin1 inhibitors effectively downregulate this signaling cascade even under hyperactive conditions, their therapeutic potential remains to be validated in preclinical models.

Background: This study investigated atherosclerosis (AS), a pivotal contributor to the onset of coronary artery disease and other cardiovascular ailments.‎.

Objectives: The presents study examined a novel therapeutic strategy combining black seed oil [Nigella sativa L. (NS)] and berberine (BBR) in a C57BL/6J mouse model of AS.

Methods: After preparing the NS nanoemulsion, gas chromatography-mass spectrometry (GC-MS) was used for analysis. A BBR-loaded black seed oil-based nanoemulsion (BBS) was developed and evaluated for its thermodynamic stability, viscosity, particle size, and dynamic light scattering (DLS) properties. Forty-eight male C57BL/6J mice (8 weeks old, 18 - 20 g) were divided into six groups and fed a modified AIN-76 diet with 25% dietary fat for 16 weeks to induce AS. Treatment began after 8 weeks through oral gavage for the remaining 8 weeks. Levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol were measured, along with the atherogenic coefficient and cardiac risk ratio. We also quantified malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities, and assessed pathological changes in cardiac and aortic tissues using hematoxylin and eosin (H&E) staining.

Results: The GC-MS analysis confirmed that NS oil met quality benchmarks, displaying stability with a zeta potential of -18.4 mV. The study showed a Polydispersity Index (PDI) of 0.3019 and a Z-average of 250.4 nm. The BBS improved lipid profiles in mice, increasing HDL and decreasing LDL, TG, and total cholesterol, thereby reducing cardiac risk. The formulation exhibited strong antioxidant effects, with reduced MDA levels and enhanced SOD, GPX, and CAT activities. Pathological observations supported these biochemical results.

Conclusions: Our findings suggest that BBS offers valuable insights into the mechanisms underlying atherosclerotic disease. This understanding could pave the way for novel approaches to cardiovascular health and the development of effective preventive strategies.

Context: Multiple sclerosis (MS) is a devastating autoimmune neurodegenerative disease, for which disease-modifying drugs (DMDs) have been associated with secondary autoimmune dermatological disorders.

Objectives: This systematic review of case reports seeks to examine documented case reports involving biological medications utilized in managing MS attacks and disease progression that correlate with such dermatological complications.

Evidence acquisition: A systematic search was conducted in the Google Scholar, Scopus, and PubMed databases for studies published until January 2024. The search strategy employed combinations of keywords such as "multiple sclerosis" with specific biological agents ("Natalizumab" OR "Ocrelizumab" OR "Rituximab" OR "Alemtuzumab" OR "Ofatumumab" OR "Ublituximab") and "case report", incorporating relevant Medical Subject Headings (MeSH) terms. All articles, if full texts were available, on case reports and case series of autoimmune dermatological complications of biological medication of MS were analyzed. The quality of the case reports was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist.

Results: A total of 19 articles fulfilled the inclusion criteria and were included in this review. The highest frequency of secondary autoimmune complications was documented with alemtuzumab administration, whereas rituximab demonstrated the lowest incidence of dermal autoimmune manifestations in MS patients.

Conclusions: The employed injectable MS immunotherapies demonstrate various autoimmune adverse reactions that have been documented across numerous case reports. This review examines different categories of secondary autoimmune complications and explores the theoretical mechanisms underlying their development.

Background: Diabetic cardiomyopathy (DCM) involves ferroptosis, an iron-dependent cell death pathway. Ellagic acid (EA), a natural antioxidant flavonoid, may offer therapeutic potential; however, its mechanisms in DCM remain unexplored.

Objectives: This study investigated the cardioprotective effects of EA in experimental DCM, focusing on its capacity to mitigate ferroptosis via the sirtuin 1 (SIRT1)/p53 pathway.

Methods: The EA (25, 50, or 100 mg/kg/day) was orally administered to streptozotocin (STZ)-induced diabetic rats for 60 days. We assessed cardiac function, histology, metabolic parameters, oxidative stress, inflammation, and key markers of ferroptosis and the SIRT1/p53 axis. Data were analyzed by one-way analysis of variance (ANOVA) with Tukey's post-hoc test.

Results: The EA treatment dose-dependently attenuated cardiac hypertrophy, myocardial injury, and metabolic dysregulation, with maximal benefits at 100 mg/kg. It also reduced oxidative stress and inflammation. Crucially, EA inhibited ferroptosis, as evidenced by reduced iron overload and upregulation of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). These benefits were associated with the upregulation of SIRT1 and downregulation of p53 in cardiac tissue.

Conclusions: The EA mitigates DCM by suppressing ferroptosis, potentially through modulation of the SIRT1/p53 pathway, thereby improving cardiac function and metabolic homeostasis. However, as this study utilized an STZ-induced model of type 1 diabetes, further research is warranted to confirm its efficacy in type 2 diabetic contexts.