Naunyn-Schmiedeberg's archives of pharmacology最新文献

Oswald Schmiedeberg was born in one of the former Baltic provinces of Russia. He studied medicine in Dorpat (Tartu) and joined the Institute of Pharmacology of Rudolf Buchheim in Dorpat. After promotion (1866) and habilitation (1868), he succeeded Buchheim as director of the institute. During this time, he further developed the experimental methods leading to the improvement of pharmacological knowledge introduced by Buchheim. In 1872, he became director of the Institute of Pharmakologie of the newly founded Kaiser-Wilhelm University in Strasbourg. He held this position for over 42 years until the end of the World War 1 when all Germans had to leave the former Reichsland Elsass-Lothringen. He settled next to his friend and colleague Naunyn in Baden-Baden, where he died in 1921. Holmstedt and Liljestrand's (1963) History of Pharmacology and Toxicology noted, "Schmiedeberg was undoubtedly the most prominent pharmacologist of his time." He had about 120 pupils, about 40 of them occupied pharmacology chairs throughout the world. In the USA, John Jacob Abel, after his return to the USA, became the "father of American pharmacology". In 1873, Schmiedeberg, together with the pathologist Klebs (Prague) and the clinician Naunyn (Königsberg), founded the Archiv für experimentelle Pathologie und Pharmakologie. When Naunyn died in 1925, the periodical was named Naunyn-Schmiedeberg's Archiv, from volume 110 onwards. In 1969, the designation "experimental pathology" was dropped, since nearly all papers submitted for some time past dealt with pharmacology. In 1883, Schmiedeberg published the Grundriss der Arzneimittellehre, the later edits with the title Grundriss der Pharmakologie in Bezug auf Arzneimittellehre und Toxikologie.

It has been reported that the gut-liver axis and intestinal microbiome contribute crucially to different liver diseases. So, targeting this hepato-intestinal connection may provide a novel treatment modality for hepatic disorders such as drug-induced liver injury (DILI). The present study thought to investigate the protective effect of turmeric (TUR) on metronidazole (MNZ)-induced liver damage and the possible association of the gut-liver axis and gut microbiota as a suggested underlying mechanism. In the first experiment, a MNZ-induced liver injury rat model was reproduced after 130 mg/kg oral MNZ administration for 30 days. Meanwhile, the treatment group was orally treated with 100 mg/kg turmeric daily. In the second experiment, fecal microbiome transplantation (FMT) was conducted, in which the fecal microbiome of each group in the first experiment was transplanted to a healthy corresponding group in the second experiment. The liver enzymes (aminotransferase (ALT) and aspartate aminotransferase (AST)) and histopathological examination were estimated to assess liver function. Inflammatory cytokines and oxidative markers were evaluated in the liver tissues. Histological analysis, intestinal barrier markers, and expression of tight junction proteins were measured for assessment of the intestinal injury. Changes in the gut microbial community and possible hepatic bacterial transmission were analyzed using 16S rRNA sequencing. MNZ induced intestinal and liver injuries which were significantly improved by turmeric. Increased firmicutes/bacteroidetes ratio and bacterial transmission due to gut barrier disruption were suggested. Moreover, TUR has maintained the gut microbial community by rebalancing and restoring bacterial proportions and abundance, thereby repairing the gut mucosal barrier and suppressing bacterial translocation. TUR protected against MNZ-induced gut barrier disruption. Reshaping of the intestinal bacterial composition and prohibition of the hepatic microbial translocation were suggested turmeric effects, potentially mitigating MNZ-related liver toxicity.

The role of neuroinflammation in the pathogenesis of depression has prompted the search for new antidepressants. Troxerutin, a bioflavonoid with anti-inflammatory and antioxidant properties, has shown promise, but its impact on neurobehavioral functions remains poorly understood. This study aimed to investigate the antidepressant potential of troxerutin and its effect on the neuroinflammatory response. Here, we exposed male Swiss mice (n = 5/group) to various treatments, including naive and negative controls receiving distilled water, troxerutin-treated groups administered at different doses (10, 20, 40 mg/kg, i.p.), and an imipramine-treated group (25 mg/kg, i.p.). After seven days of treatment, with the exception of the naive group, mice were administered a single dose of lipopolysaccharide (LPS, 0.83 mg/kg). Behavioral evaluations, consisting of the novelty-suppressed feeding (NSF) test, forced swim test (FST), and open field test (OFT), were conducted. Additionally, brain samples were collected for biochemical and immunohistochemical analyses. Troxerutin significantly reduced immobility time in the FST and mitigated behavioral deficits in the NSF test. Additionally, troxerutin increased glutathione (GSH) and superoxide dismutase (SOD) levels while reducing nitrite, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) levels compared to the negative control. Immunohistochemistry analysis revealed decreased expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) in troxerutin-treated mice. Overall, these findings suggest that troxerutin exerts significant antidepressive-like effects, likely mediated by its anti-inflammatory and antioxidant mechanisms. The reduction in neuroinflammatory and oxidative stress biomarkers, along with the improvement in behavioral outcomes, underscores troxerutin's potential as a therapeutic agent for depression.

Glioblastoma (GBM) is an aggressive type IV brain tumor that originates from astrocytes and has a poor prognosis. Despite intensive research, survival rates have not significantly improved. Noncoding RNAs (ncRNAs) are emerging as critical regulators of carcinogenesis, progression, and increased treatment resistance in GBM cells. They influence angiogenesis, migration, epithelial-to-mesenchymal transition, and invasion in GBM cells. ncRNAs, such as long ncRNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are commonly dysregulated in GBM. miRNAs, such as miR-21, miR-133a, and miR-27a-3p, are oncogenes that increase cell proliferation, metastasis, and migration by targeting TGFBR1 and BTG2. In contrast, lncRNAs, such as HOXD-AS2 and LINC00511, are oncogenes that increase the migration, invasion, and proliferation of cells. CircRNAs, such as circ0001730, circENTPD7, and circFOXO3, are oncogenes responsible for cell growth, angiogenesis, and viability. Developing novel therapeutic strategies targeting ncRNAs, cell migration, and angiogenesis is a promising approach for GBM. By targeting these dysregulated ncRNAs, we can potentially restore a healthy balance in gene expression and influence disease progression. ncRNAs abound within GBM, demonstrating significant roles in governing the growth and behavior of these tumors. They may also be useful as biomarkers or targets for therapy. The use of morpholino oligonucleotides (MOs) suppressing the oncogene expression of HOTAIR, BCYRN1, and cyrano, antisense oligonucleotides (ASOs) suppressing the expression of ncRNAs such as MALAT1 and miR-10b, locked nucleic acids (LNAs) suppressing miR-21, and peptide nucleic acids (PNAs) suppressing the expression of miR-155 inhibited the PI3K pathway, tumor growth, angiogenesis, proliferation, migration, and invasion. Targeting oncogenic ncRNAs with RNA-interfering strategies such as MOs, ASOs, LNAs, CRISPR-Cas9 gene editing, and PNA approaches may represent a promising therapeutic strategy for GBM. This review emphasizes the critical role of ncRNAs in GBM pathogenesis, as well as the potential for new therapeutic strategies targeting these pathways to improve the prognosis and quality of life for GBM patients.

Paclitaxel, a potent chemotherapeutic agent derived from the bark of the Pacific yew tree, has demonstrated significant efficacy in the treatment of various cancers, including colon cancer. This comprehensive review delves into the conventional treatments for colon cancer, emphasizing the crucial role of paclitaxel in contemporary management strategies. It explores the intricate process of sourcing and synthesizing paclitaxel, highlighting the importance of its structural properties in its anticancer activity. The review further elucidates the mechanism of action of paclitaxel, its pharmacological effects, and its integration into chemotherapy regimens for colon cancer. Additionally, novel drug delivery systems, such as nanocarriers, liposomes, nanoparticles, microspheres, micelles, microemulsions, and niosomes, are examined for their potential to enhance the therapeutic efficacy of paclitaxel. The discussion extends to recent clinical trials and patents, showcasing advancements in paclitaxel formulations aimed at improving treatment outcomes. The review concludes with prospects in the field underscoring the ongoing innovation and potential breakthroughs in colon cancer therapy.

Clozapine has been considered the "gold standard" in the treatment of schizophrenia for many years. Clozapine has a superior effect, particularly in the treatment of negative symptoms and suicidal behaviour. However, due to its numerous adverse reactions, clozapine is mainly used for treatment-resistant schizophrenia. The aim of this paper is to analyze the results of clinical studies on clozapine from 2012-2022. PubMed was used as the database. Sixty-four studies were included and categorised by topic. The pharmacokinetic properties of clozapine tablets and a clozapine suspension solution did not differ markedly. Clozapine was superior to olanzapine and risperidone in reducing aggression and depression. A long-term study showed that metabolic parameters changed comparably with olanzapine and clozapine after 8 years. Risperidone and ziprasidone can be used as an alternative to clozapine. Scopolamine, atropine drops, and metoclopramide are effective in the treatment of clozapine-induced hypersalivation. Eight drugs, including liraglutide, exenatide, metformin, and orlistat, are potentially effective in the treatment of clozapine-induced weight gain. Ziprasidone, haloperidol, and aripiprazole showed a positive effect on symptoms when added to clozapine. No investigated drug was superior to clozapine for the treatment of schizophrenia. Ziprasidone and risperidone can also be used well for the treatment of schizophrenia. In the treatment of clozapine-induced hypersalivation and weight gain, some drugs proved to be effective.

The main objective of this study was to investigate the potential efficacy of carvacrol (CAR) in mitigating bleomycin (BLM)-induced pulmonary fibrosis (PF). Sixty-six male Wistar rats were assigned into two main groups of 7 and 21 days. They were divided into the subgroups of control, BLM, CAR 80 (only for the 21-day group), and CAR treatment groups. The CAR treatment groups received CAR (20, 40, and 80 mg/kg, orally) for 7 or 21 days after an instillation of BLM (5 mg/kg, intratracheally). Results indicated that BLM significantly increased total cell count in bronchoalveolar lavage fluid and the percentages of neutrophils and lymphocytes, and reduced the percentage of macrophages. CAR dose-dependently decreased total cell count and the percentage of neutrophils and lymphocytes. CAR significantly reduced thiobarbituric acid reactive substances and hydroxyproline levels and elevated the total thiol level and catalase, superoxide dismutase, and glutathione peroxidase activities in BLM-exposed rats. Furthermore, CAR decreased the transforming growth factor-β1, connective transforming growth factor, and tumor necrosis factor-α on days 7 and 21. BLM increased interferon-γ on day 7 but decreased its level on day 21. However, CAR reversed interferon-γ levels on days 7 and 21. Based on histopathological findings, BLM induced inflammation on days 7 and 21, but for induction of fibrosis, 21-day study showed more fibrotic injuries than the 7-day group. CAR showed the improvement of fibrotic injuries. The effect of CAR against BLM-induced pulmonary fibrosis is possibly due to its antioxidant, anti-inflammatory, and antifibrotic activity.

Epicatechin (Epi) is one of the most abundant flavonoids present in different fruits and tea leaves. Emerging research illuminates the promising potential of catechins to serve as a shield against the damaging effects of arsenic (As) exposure in diverse organs.This study sought to discern whether Epi exhibits a therapeutic efficacy against arsenic-induced neurotoxicity in a murine model.The Naval Medical Research Institute (NMRI) mice were randomly partitioned into six distinct groups, which included a control group receiving normal saline, a group receiving a daily oral dose of arsenic (10 mg/kg) for 5 weeks, groups receiving As (10 mg/kg/day) orally for 5 weeks along with different doses of Epi (25-100 mg/kg) orally for the last 2 weeks, and a group receiving Epi (100 mg/kg) orally for 2 weeks. To assess the potential effects of Epi, neurobehavioral tests, various parameters of oxidative stress, and inflammation were evaluated.The findings of this investigation revealed that As-induced neurobehavioral toxicity was associated with a notable surge in lipid peroxidation and nitric oxide (NO) concentration, accompanied by a reduction in the levels of antioxidant markers. As heightened pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) levels were observed alongside amplified nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. However, treatment with Epi reversed these effects.On the whole, these findings indicate that Epi may hold promise therapeutic efficacy on As-induced neurotoxicity by improving antioxidant status and mitigating oxidative stress and inflammation. Nevertheless, further research is imperative to comprehensively grasp the potential protective effects of Epi in this particular context.

This study was carried out to verify the evidence regarding the effectiveness and safety of sotrovimab in patients with COVID-19. This is a systematic review of randomized clinical trials retrieved from the PubMed, Embase, Scopus, Lilacs, and Cochrane Library databases. The risk of bias was measured using the Cochrane Risk and Bias Checklist (RoB 2). For the meta-analysis, RStudio Version 2024.04.2 software was used. The certainty of evidence was assessed using GRADE. The study protocol was registered in PROSPERO (CRD42022355786). A total of 1893 studies were identified and four were included in the study. The total population consisted of 5470 patients with COVID-19, 1921 (35%) in the sotrovimab group and 3549 (65%) in the control group (placebo or BRII-196 + BRII-198 or casirivimab + imdevimab or bamlanivimab + etesevimab, administered in a similar way to sotrovimab, in a single dose with a 60-min intravenous infusion). For the effectiveness outcome, three studies presented low risk and one high risk of bias, while for safety all presented high risk of bias. The meta-analysis showed no significant difference between the sotrovimab and control groups in terms of hospitalization rates (95% confidence interval (CI) - 2.10-0.51; p = 0 > 0.05), use of invasive mechanical ventilation (95% CI - 2.78-0.65; p = 0.35) and mortality (95% CI - 0.92-0.59; p = 0.39). However, sensitivity analysis showed that sotrovimab may be effective in reducing hospitalization rates compared to the control (IV =  - 1.57; 95% CI - 2.41-0.73; p = 0.99). The use of sotrovimab in the treatment of patients with COVID-19 had no significant impact on mortality and need for mechanical ventilation and did not appear to be safer compared to controls. However, there was evidence of effectiveness in reducing the rate of hospitalization, although the certainty of the evidence is moderate and the risk of bias is high.

Fisetin, a polyphenolic flavonoid, exhibits numerous pharmacological activities against metabolic syndromes. The present research aims to explore the therapeutic efficacy of fisetin in experimental polycystic ovary syndrome (PCOS). Female Sprague-Dawley rats were administered mifepristone (20 mg/kg/day) to induce PCOS. PCOS rats were treated with fisetin (20 mg/kg and 40 mg/kg) and further compared with metformin HCl, the conventional drug for PCOS. The mechanism of fisetin was explored using dorsomorphin (an AMPK inhibitor). Then, rats were sacrificed for further analysis of biochemical and histological parameters. PCOS rats exhibited irregular estrous cycles, increased serum testosterone (4.72 ± 0.139 ng/ml), estradiol (750.2 ± 16.56 pg/ml), LH (30.33 ± 1.563 mIU/ml), HOMA-IR (1.115 ± 0.049), TNF-α (86.59 ± 3.93 pg/ml), IL-6 (55.34 ± 4.432 pg/ml), and TBARS (3.867 ± 0.193 µmol/mg) along with declined progesterone (11.67 ± 1.54 ng/ml), FSH (13.33 ± 1.256 mIU/ml), GSH (33.47 ± 1.348 µmol/mg) levels, and SOD (2.163 ± 0.298 U/mg) activity as compared to normal control group. Fisetin high dose significantly lowers testosterone (3.014 ± 0.234 ng/ml), estradiol (533.7 ± 15.39 pg/ml), LH (16.67 ± 1.62 mIU/ml), HOMA-IR (0.339 ± 0.20), TNF-α (46.02 ± 2.66 pg/ml), IL-6 (31.77 ± 3.47 pg/ml), and TBARS (1.747 ± 0.185 µmol/mg) and enhances progesterone (33.17 ± 1.447 ng/ml), FSH (27.17 ± 1.42 mIU/ml), GSH (60.35 ± 1.1.102 µmol/mg) levels, and SOD (4.513 ± 0.607 U/mg) activity. The histology of ovarian tissues shows a significant increase in cystic follicles in PCOS rats compared with the normal control group. These alterations were attenuated with fisetin treatment. Administration of dorsomorphin with fisetin can reverse the beneficial effects of fisetin in PCOS rats. Altogether, these present findings highlight the potential of fisetin as a promising therapeutic intervention for the management of PCOS by modulating AMPK/SIRT1 signaling in rats.