Naunyn-schmiedebergs Archives of Pharmacology最新文献

Polycystic ovary syndrome (PCOS) is a prevalent gynecological-endocrinological disorder characterized by hyperandrogenism, menstrual irregularities, and metabolic disturbances. Recent research has highlighted the role of oxidative stress and chronic inflammation in exacerbating PCOS symptoms and impeding reproductive outcomes. Astaxanthin, a potent antioxidant found in marine organisms, has been suggested as a potential therapeutic intervention due to its ability to reduce oxidative stress and inflammation. This meta-analysis systematically reviews randomized controlled trials assessing the impact of astaxanthin supplementation on oxidative stress and reproductive outcomes in women with PCOS. Data from four trials were analyzed, focusing on markers of oxidative stress and reproductive health metrics. The meta-analysis utilized fixed and random-effects models to synthesize results, with heterogeneity assessed using Chi-square and I² statistics. The findings indicate that while astaxanthin significantly improves markers of total antioxidant capacity (TAC) in follicular fluid, it does not show a consistent effect on other oxidative stress biomarkers such as malondialdehyde (MDA), catalase (CAT), or superoxide dismutase (SOD). Reproductive outcomes, including oocyte quality and the number of high-quality embryos, showed moderate improvements, although effects on fertilization rates and pregnancy outcomes were insignificant. The analysis highlights variability in study designs and dosing, suggesting a need for further research with standardized protocols and larger sample sizes. Future studies should focus on determining optimal dosing, exploring mechanistic pathways, and investigating the combined effects of astaxanthin with other interventions. Longitudinal studies are needed to assess long-term benefits and safety, and personalized approaches could enhance treatment efficacy for individuals with PCOS.

The Deutsche Apotheker Zeitung (DAZ, German Pharmacist Journal) is an independent pharmaceutical newspaper focusing on science and practice, mainly for the profession of pharmacist. In this study, drug advertising in the DAZ was analysed. To our knowledge, there is little scientific data available on drug advertising in professional journals. We assumed that professional journals provide particularly good background information on the advertised drugs because they are targeted to specialists. All non-prescription medicines and preparations that fall under the Medicines Advertising Law (Heilmittelwerbegesetz, HWG) were studied. The Medicines Advertising Law regulates the legal procedure for advertising medicinal products in Germany. The 167 product advertisements from the 52 issues of 2021 were analysed and checked for compliance with the Medicines Advertising Law. We identified significant deficiencies in compliance with the legislation. These included the lack of mandatory information required by the Medicines Advertising Law, for example the indication of adverse drug reactions and the listing of contraindications. There are very few peer-reviewed references on the efficacy of the advertised preparations. A scientific validation was carried out using the PubMed database, with the result that scientific information was available only for 1/3 of the advertisements. In addition, the appearance and target groups as well as social structures, images and feelings conveyed by the advertising were analysed. This study provides insights into the mechanisms of drug advertising in professional journals, which have not yet been researched to any great extent. Even in professional journals, pharmacological evidence plays a much smaller role than marketing, psychology and traditional social values. It seems that drug manufacturers deliberately ignore the German Medicines Advertising Law to advertise their products in the best possible way. Stricter legal controls should be put in place to prevent this practice and protect consumers from misinformation. This will increase drug safety.

Recent advancements in nanotechnology have sparked interest in the synthesis of chitosan nanoparticles and their potential applications in medicine. This study investigates the synthesis of chitosan nanoparticles infused with thiazolidinedione and magnolol (TZ/ML-ChNPs) and their therapeutic effects on gestational diabetes mellitus (GDM) in experimental mice. Using streptozotocin-induced diabetic pregnant mice as a model, the study examines the anti-diabetic effects of TZ/ML-ChNPs in vitro and explores possible mechanisms of action. Results show a notable decrease in α-amylase and α-glucosidase activities in TZ/ML-ChNPs-treated samples. Cytocompatibility and flow cytometry analysis in streptozotocin-induced diabetic pregnant mice conducted on RIN-5F cell line demonstrate the safety profile of TZ/ML-ChNPs. The primary objective of this research is to assess whether TZ/ML-ChNPs can mitigate hyperlipidemia and oxidative stress in diabetic pregnant mice. Chitosan nanoparticles with thiazolidinedione and magnolol have therapeutic effects that may be used in clinical and pharmaceutical applications.

Graphical abstract

Medical devices play an essential role in the delivery of healthcare but its use is not entirely risk free. There are several instances where it causes mortality or morbidity among users. It is important to evaluate the risks involved at every stage of its application to bring improvement in the standard of healthcare. For the purpose Materiovigilance Program of India was launched on July 6, 2015. Despite these efforts, available data suggests that reporting of adverse events is very low. The present study aims to identify barriers that influence the reporting of adverse events of medical devices and outline a strategy to overcome these barriers. Systemic review method has been adopted to achieve these ends. Thirty-one papers have been selected based on the inclusion criteria related to objective of the study. Lack of awareness, attitude, and resources are found to be major barriers at the individual level for not reporting adverse effects of medical devices. The organizational factors such as hierarchical set up, lack of time and incentives, and furthermore lack of industry responsiveness have been identified as prominent barriers to the reporting of adverse events. In order to improve the reporting level, it is important to make access and contact easier with the reporting system. Engaging healthcare professionals at various levels by acknowledging and appreciating their contribution. The adverse events of medical devices should not be restricted to physicians; only rather other health care professional such as nurses, pharmacists, and technicians should also be encouraged to report any adverse event of medical devices.

Glioblastoma multiforme (GBM) is a highly malignant central nervous system tumor with a poor prognosis. Developing new therapeutic drugs is crucial. This study evaluates deoxyelephantopin (DET), a major component of *Elephantopus scaber* L., for its potential anti-GBM effects. The effects of DET on GBM cell lines were investigated using the MTT assay and Annexin-V kit to assess cell death and apoptosis. Western blot analysis examined apoptosis and cell cycle-related proteins. ELISA kits measured VEGF and TGF-β levels. In vivo, NOD SCID mice were injected with GL-261 cells and treated with DET to evaluate tumor growth and survival. DET inhibited GBM cell growth in a time- and dose-dependent manner. MTT and Annexin-V assays confirmed cell death and apoptosis. Western blot analysis showed DET downregulated Bcl-2 and increased caspase-3, Bax, and cytochrome c levels. ELISA results indicated that DET suppressed VEGF and TGF-β expression. DET treatment also decreased phosphorylation of AKT and STAT-3, CDK4, cyclin D2, MMP2, and MMP9 levels. In vivo, DET significantly inhibited tumor growth and improved survival rates in mice. DET exhibits significant in vitro and in vivo anticancer effects, making it a promising candidate for further research and potential clinical application against GBM.

Psoriasis is a life-long immune-mediated dermatosis with thickened, reddish, and flaky skin patches. Canagliflozin is a gliflozin antidiabetic with non-classical remarkable antioxidative, anti-inflammatory, anti-proliferative, and immune-modulating effects. The aim of this study is to examine the probable effects of topical canagliflozin on a mouse model of imiquimod-provoked psoriasis-like dermatitis. The study evaluated 20 Swiss white mice, sorted haphazardly into 4 groups of 5 animals each. Every mouse, with the exception of the control group, had imiquimod applied topically to their shaved backs for 7 days. The control group included healthy mice that were not given any treatment. Mice in the other three groups underwent topical treatment with vehicle (induction group), 0.05% clobetasol propionate ointment (clobetasol group), or 4% canagliflozin emulgel (canagliflozin 4% group) on exactly the same day as imiquimod cream was administered. Topical canagliflozin markedly lowered the intensity of imiquimod-provoked psoriasis eruptions, featuring redness, glossy-white scales, and acanthosis, while also correcting histopathological aberrations. Canagliflozin administration to imiquimod-exposed animals resulted in significantly decreased cutaneous concentrations of inflammatory mediators such as IL-8, IL-17, IL-23, and TNF-α, with raised levels of IL-10. Canagliflozin further lowered proliferative factors involving Ki-67 and PCNA, diminished oxidative indicators such as MDA and MPO, and augmented the activity of antioxidant markers, notably SOD and CAT. Canagliflozin might alleviate the imiquimod-induced animal model of psoriasis, probably thanks to its profound anti-inflammatory, antioxidant, antiangiogenic, and antiproliferative activities.

Graphic Abstract

The objective of this study was to evaluate the incidence, clinical features, and risk factors of generic tigecycline-associated hypofibrinogenemia. A single-center retrospective study was conducted in adult patients treated with generic tigecycline. Clinical data were extracted from the electronic medical records. The endpoint was tigecycline-related hypofibrinogenemia, defined as a condition with no abnormality in fibrinogen before tigecycline application, but developing hypofibrinogenemia upon prescription. The risk factors were determined by logistic regression analysis, and the ROC curve was subsequently established. A total of 240 adults prescribed generic tigecycline from May 1st to November 30th 2023 were included. It was shown that hypofibrinogenemia is a frequent side effect of generic tigecycline, with an adverse reaction rate of 42.9% (103/240). However, the incidence of adverse reactions to generic drugs was lower than in previous studies. The cumulative dose of tigecycline (OR:1.002, 95%CI 1.001–1.002, P < 0.001), baseline FIB (OR:0.995, 95%CI 0.992–0.997, P < 0.001), baseline PT (OR:1.247, 95%CI 1.071–1.452, P = 0.004) and baseline ALB (OR:0.931, 95%CI 0.879–0.986, P = 0.025) were identified as independent prognostic factors of tigecycline-related hypofibrinogenemia. We recommend intensive monitoring of coagulation function in patients exhibiting the aforementioned risk factors for generic tigecycline-associated hypofibrinogenemia to ensure patients safety.

Postmenopausal osteoporosis is a common chronic medical illness resulting from an imbalance between bone resorption and bone formation along with microarchitecture degeneration attributed to estrogen deficiency and often accompanied by other medical conditions such as weight gain, depression, and insomnia. Semaglutide (SEM) is a recently introduced GLP-1 receptor agonist (GLP-1RA) for the treatment of obesity and type 2 diabetes mellitus by mitigating insulin resistance. It has been discovered that the beneficial effects of GLP-1 are associated with alterations in lipolysis, adipogenesis, and anti-inflammatory processes. GLP-1 analogs transmit signals directly to adipose tissue. Mesenchymal stem cells (MSCs) are multidisciplinary cells that originate from bone marrow, migrate to injury sites, and promote bone regeneration. MSCs can differentiate into osteoblasts, adipose cells, and cartilage cells. Our aim is to investigate the role of semaglutide on bone formation and the Wnt signaling pathway. Osteoporosis was induced in female rats by ovariectomy, and the ovariectomized rats were treated with alendronate as standard treatment with a dose of 3 mg/kg orally and semaglutide with two doses (150 mcg/kg and 300 mcg/kg) S.C. for 10 successive weeks. Semaglutide ameliorates bone detrimental changes induced by ovariectomy. It improves bone microarchitecture and preserves bone mineral content. Semaglutide ameliorates ovariectomy-induced osteoporosis and increases the expression of β-catenin, leading to increased bone formation and halted receptor activator of nuclear factor kappa-Β ligand (RANKL’s) activation. Semaglutide can be used as a potential prophylactic and therapeutic drug against osteoporosis, possibly by activating Wnt signaling and decreasing bone resorption.

Graphical Abstract

Dichlorvos is an organophosphate pesticide that is commonly used for agricultural and domestic control of pests and insects. Despite its usefulness, it exerts reproductive toxicity and induces male sexual dysfunction. On the other hand, curcumin has been reported to improve sexual dysfunction. However, till date, no study has reported the impact of curcumin on dichlorvos-induced sexual dysfunction. This study investigated the effect and associated mechanism of curcumin on dichlorvos-induced sexual dysfunction. Thirty-two male Wistar rats were randomized into four groups; the control (1 mL of olive oil), curcumin-treated (100 mg/kg), DDVP-treated (98.54 g/m³ of dichlorvos by inhalation), and DDVP + Curcumin-treated. Dichlorvos induced sexual dysfunction as depicted by reduced motivation to mate (8.38 ± 0.18 vs. 4.00 ± 0.33, P < 0.0001), prolonged latencies (46.63 ± 1.30 vs. 98.75 ± 1.32, P < 0.0001) and reduced frequencies of mount (14.88 ± 0.52 vs. 8.63 ± 0.38), intromission (9.38 ± 0.50 vs. 3.75 ± 0.31, P < 0.0001), and ejaculation (7.63 ± 0.38 vs. 1.50 ± 0.19, P < 0.0001). These findings were accompanied by suppression of hypothalamic-pituitary–testicular axis, evidenced by marked reductions in circulating FSH (60.00 ± 1.04 vs. 21.13 ± 0.52, P < 0.0001), LH (46.38 ± 1.38 vs. 19.00 ± 0.46, P < 0.0001), and testosterone (6.01 ± 0.50 vs. 0.74 ± 0.05, P < 0.0001). Nonetheless, the administration of curcumin in dichlorvos-exposed rats significantly attenuated dichlorvos-induced sexual dysfunction by improving the assessed indices of male sexual act. Also, curcumin significantly increased serum levels of FSH (21.13 ± 0.52 vs. 47.25 ± 0.10, P < 0.0001), LH (19.00 ± 0.46 vs. 43.00 ± 1.49), and testosterone (0.74 ± 0.05 vs. 3.98 ± 0.08, P < 0.0001). This study revealed that curcumin attenuated dichlorvos-induced sexual dysfunction by activating the hypothalamic-pituitary–testicular axis and upregulating circulating testosterone.

Background

Rosemary (Rosmarinus officinalis) contains alkaloids, phenolic acids, saponins, tannins, diterpenes, flavonoids, and essential oils and has antioxidant, anti-inflammatory, antibacterial, anticancer, neuroprotective, cardioprotective, and hepatoprotective effects. While rosemary is generally considered safe for consumption and topical application, allergic reactions and dermatitis have been reported in some individuals. This paper provides an in-depth review of the current studies on rosemary toxicity, shedding light on its potential adverse effects and underlying mechanisms.

Methods

Google Scholar, PubMed, Scopus, and Web of Science were used to perform extensive research from the inception of these databases until February 2024.

Results

The toxicological effects explored include affecting several organs such as the liver and kidney by causing atrophic and degenerative changes, increasing blood urea nitrogen (BUN), aspartate aminotransferase (AST), and reducing total serum protein levels. Rosemary may induce reproductive toxicity by decreasing spermatogenesis in the testes, testosterone, sperm density, and motility. It might also trigger genotoxicity and anomalies in fetuses by increasing cytoplasmic membrane shrinkage, the formation of apoptotic bodies, internucleosomal deoxyribonucleic acid (DNA) fragmentation, and DNA ladder formation.

Conclusion

While rosemary is considered safe for food preservation, caution is warranted regarding chronic and high doses due to potential adverse effects on the kidneys, liver, reproductive system, and teratology. Additionally, it underscores the significance of considering drug interactions. The article also highlights the importance of considering toxicological data in realistic exposure situations and discusses the relevance of these findings for human health. Hence, further research is recommended to enhance our understanding of the toxicity profile associated with rosemary.