Naunyn-Schmiedeberg's archives of pharmacology最新文献

Nonsteroidal anti-inflammatory drug (NSAID)-induced kidney injury is one of the most common causes of renal failure. The exact pathogenesis of NSAID induced kidney injury is not fully known and the treatment is still challenging. Artemisinin (ART) gains more attention by its potent biological activities in addition to its antimalarial effect. In our research, we evaluated the preventive and therapeutic effects of ART in Diclofenac (DIC) induced kidney injury through its effect on mitochondria and regulation of sirtuin 3 (SIRT3). Thirty adult male Sprague Dawley rats were divided into five groups: control, ART, DIC, DIC + ART prophylactic, and DIC followed + ART therapeutic groups. At the end of the study, animals were scarified and the following parameters were evaluated: serum urea and creatinine, renal malondialdehyde (MDA), superoxide dismutase (SOD) and nitrate. SIRT3 was detected by western blotting and real-time PCR. Mitochondrial related markers (PGC-1α, Drp1, and mitochondrial ATP) were detected by immunoassay. Caspase-3 and LC3 II expression in kidney tissues were demonstrated by immune-histochemical staining. The kidney specimens were stained for H&E and PAS special stain. Electron microscopy was done to detect mitochondrial morphology. ART improved renal function test, oxidative stress, SIRT3 level, mitochondrial function, LC3 II expression and decrease caspase-3. Histopathological examination confirmed ART alleviation as determined by light or electron microscopy. ART can modulate biochemical and pathological changes in DIC-induced kidney injury and can be considered a new possible therapeutic approach for DIC-induced kidney injury through its effect on SIR3 and maintenance of mitochondrial homeostasis.

Edaravone (EDA) has been found to exert protective effects on kidney injury. Nevertheless, the functions of EDA in kidney stones as well as the potential mechanism are vague. Calcium oxalate (CaOx) was used to induce kidney stones cell model with human renal tubular epithelial cell line HK-2. CCK-8 assay was employed to detect cell viability injury. Oxidative stress was measured by DCFH-DA staining and detection of MDA, SOD, and GSH. Staining of FerroOrange and western blot were applied for ferroptosis. In addition, autophagy was elucidated by western blot and immunofluorescence staining. The data showed that CaOx treatment aggravated HK-2 cell viability injury, increased the levels of ROS, MDA, and Fe²⁺ in HK-2 cells, and reduced the contents of SOD and GSH. Additionally, CaOx enhanced the expression of KIM1, TFR1, LC3II/LC31, and BECLIN1 in HK-2 cells, while resulting in a decrease in the expression of GPX4, SLC7A11, and P62. Pretreatment of EDA mitigated CaOx-induced oxidative stress and ferroptosis, as well as autophagy in renal tubular epithelial cells. However, autophagy inducer rapamycin (Rap) reversed the protective role of EDA on renal tubular epithelial cell injury, oxidative stress, and ferroptosis. In conclusion, EDA contributes to suppressing oxidative stress and ferroptosis in CaOx-induced HT22 cells by restraining autophagy, which may be a potential candidate for the treatment of kidney stones caused by renal tubular epithelial cell damage.

Silver nanoparticles have gained significant attention recently due to their unique antibacterial properties, making them promising candidates for wound care applications. This study proposes a novel approach for advanced wound care using a silver nanoparticle-impregnated biogenic spray hydrogel supplemented with collagen and chitosan. Silver nanoparticles were incorporated into the hydrogel (optimized by a QbD approach) to impart antimicrobial activity, crucial for combating wound infections and promoting faster healing. The study assessed the physical and chemical properties of the biogenic hydrogel, including its viscosity, pH, and nanoparticle dispersion characteristics. In vitro, antimicrobial efficacy against common wound pathogens and in vivo studies using chronic wound models in small animals portrayed the immense potential of the developed biogenic hydrogel in effectively reducing the bacterial load of broad-spectrum pathogens. The hydrogel exhibited excellent biocompatibility, supporting cell proliferation and tissue repair without toxic effects. It accelerated wound healing, improved collagen deposition, and enhanced tissue regeneration in the tested animals by reducing proinflammatory cytokines, ROS, and NF-kb levels. Overall, this innovative silver nanoparticle-impregnated biogenic spray hydrogel of collagen and chitosan presents a uniform spray pattern that proved efficient, showing a promising solution for advanced wound care. Its biocompatibility, safety, anti-inflammatory, antimicrobial efficacy, and wound healing properties hold great potential for improving the management of complex wounds, opening new avenues in wound care and regenerative medicine.

For many years, pharmaceutical expenditure has been the second largest cost item for statutory health insurance funds (SHI) in Germany after hospital costs. Since prescriptions and expenditure on medicines play such a major role in the German healthcare system, the question arises as to what causes changes in prescriptions. To answer this question, the prescribing trends for the top 10 drugs in 2022 were analyzed over a period of 38 years, from 1985 to 2022. The prescribed defined daily doses (DDD) and the costs per defined daily dose for the 10 medicines were taken from the Arzneiverordnungsreport (AVR) from 1986 to 2023, and the changes in prescribing behavior and their causes were analyzed. The ten most important medicines in 2022, accounting for over 41% of all prescribed daily doses, were ramipril, candesartan, pantoprazole, amlodipine, atorvastatin, levothyroxine, torasemide, simvastatin, bisoprolol, and metoprolol. There are many different reasons for an increase in prescriptions, such as the introduction of generics, a positive study, or a price reduction. Further reasons for an increase in prescriptions are an extension of the indication or the recall of a competing medicine. A change in guidelines or the increasing treatment of laboratory values without clinical symptoms can also lead to an increase in prescriptions. There are also many different reasons for a drop in prescriptions, such as the generic launch of a competitor medicine or a positive study for a competitor medicine. Other reasons for a drop in prescriptions are a negative study or a discussion about the use of a drug. Sometimes, the reasons for prescription changes are also irrational. Overall, this is the most comprehensive long-term analysis of drug prescriptions in Germany. Our data is helpful for predicting drug prescriptions and for preventing future drug shortages not only in Germany but also worldwide.

This study aims to conduct a comprehensive bibliometric analysis of global research trends and hotspots related to the biological activities of D-limonene, a prominent monoterpene compound found in essential oils, that warrant attention. We performed a bibliometric analysis of 1928 publications sourced from the Web of Science core database, covering the period from 1994 to 2024. Utilizing CiteSpace and VOSviewer software, we analyzed publication trends, collaboration networks among countries, institutions, and authors, and explored the evolution of research themes and current hotspots through keyword analysis. Our findings indicate a rapid increase in research on D-limonene activities since 2017, with China and Brazil leading in publication output. Italy and the USA play central roles within the collaboration network. Notably, a core group of authors has yet to emerge in this field. The biological activities of D-limonene, particularly its antibacterial, antioxidant, anti-inflammatory, and antitumor properties, are widely studied. Recent research hotspots focus on its neuroprotective effects and its potential role in inhibiting antibiotic resistance. The study highlights the growing interest in D-limonene and suggests that its use as an adjuvant to enhance therapeutic efficacy through synergistic interactions with other drugs may represent a significant research direction for the future. This analysis provides valuable insights for researchers and practitioners in pharmacology and related fields, emphasizing the importance of D-limonene in advancing health-related applications.

Pneumonia is a frequent-occurring event in children death. Vitamin D (VD) can alleviate inflammatory response and it might be a promising adjunct to antibiotics for the treatment of acute childhood pneumonia. This study intended to uncover the relevant mechanism of VD in pneumonia. For simulating inflammatory condition, BEAS-2B cells were induced using lipopolysaccharide (LPS). Cell viability was detected using cell counting kit-8 (CCK-8) method, and cell apoptosis was detected using flow cytometry and western blot. Inflammatory cytokines as well as oxidative stress markers were detected using enzyme-linked immunosorbent assay (ELISA) and corresponding assays. Western blot evaluated the contents of cathepsin D (CTSD), apoptosis- and autophagy-related proteins. Through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot, the transfection efficiency of overexpression (OV)-CTSD was detected. Immunofluorescence assay detected light chain 3 (LC3II) level. Through SuperPred database analysis, VD can target CTSD. VD was revealed to suppress viability damage, inflammatory response, oxidative stress, and autophagy injury in BEAS-2B cells induced by LPS via targeting CTSD. However, the protective effects exhibited by VD against LPS-induced viability damage, inflammatory response, and oxidative stress in BEAS-2B cells were all counteracted by autophagy inhibitor 3-methyladenine (3-MA). Collectively, VD alleviated the severity of LPS-induced lung injury by promoting autophagy through targeting CTSD.

Since cancer is becoming a leading cause of death worldwide, efforts should be concentrated on understanding its underlying biological alterations that would be utilized in disease management, especially prevention strategies. Within this context, multiple bodies of evidence have highlighted leptin's practical and promising role, a peptide hormone extracted from adipose and fatty tissues with other adipokines, in promoting the proliferation, migration, and metastatic invasion of breast carcinoma cells. Excessive blood leptin levels and hyperleptinemia increase body fat content and stimulate appetite. Also, high leptin level is believed to be associated with several conditions, including overeating, emotional stress, inflammation, obesity, and gestational diabetes. It has been noted that when leptin has impaired signaling in CNS, causing the lack of its normal function in energy balance, it results in leptin resistance, leading to a rise in its concentration in peripheral tissues. Our research paper will shed highlighting on potentially targeting the leptin receptor and its cellular signaling in suppressing breast cancer progression.

This study evaluated the beneficial effects of chrysin against cyclophosphamide (CP)-induced testicular toxicity in rats across several parameters, including hormones, oxidative stress, inflammation, apoptosis, and protein expression. Rats were pretreated with oral doses of chrysin at 25, 50, or 100 mg/kg daily for 7 days. On the 8th day, all groups except controls received CP (200 mg/kg) injection. Chrysin doses continued for 7 more days. Hormones, oxidative stress markers, inflammatory cytokines, apoptosis regulators, and iron regulatory proteins were assessed. CP decreased testosterone, inhibin B, GSH, and GPx4 and increased FSH, cholesterol, MDA, IL-6, and BAX. It also drastically reduced TfR1, liprin, and IREB2. Chrysin dose-dependently counteracted these effects. The highest 100 mg/kg chrysin dose increased testosterone, inhibin B, GSH, GPx4, BCL2, TfR1, liprin, and IREB2 while decreasing FSH, cholesterol, MDA, IL-6, and BAX close to control levels. There were also significant incremental benefits for testosterone, inhibin B, and other parameters with higher chrysin doses. Chrysin dose-dependently attenuated CP-induced hormonal dysfunction, oxidative stress, inflammation, apoptosis, and iron-regulatory protein suppression. The maximum dose showed the most optimal protective effects in restoring the testicular toxicity markers. These results validate the promising spermatoprotective properties of chrysin against chemotherapeutic germ cell damage.