Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Rhizoma Paridis saponins in respiratory diseases: a narrative review of multi-target mechanisms and therapeutic potential.","authors":"Meng Gao, Xue Zhang, Yanhua Li, Yulian Hu, Guifang Sun, Fangyun Zhao, Li Zhou","doi":"10.1007/s00210-026-05707-w","DOIUrl":"10.1007/s00210-026-05707-w","url":null,"abstract":"<p><p>Rhizoma Paridis saponins (RPS) are bioactive constituents of Rhizoma Paridis with reported anti-inflammatory and antitumor activities. However, their roles in respiratory diseases remain incompletely understood. This study is a narrative review rather than a systematic review. A narrative literature review was conducted using PubMed and CNKI databases to retrieve studies published between 2014 and 2025. Keywords included \"Rhizoma Paridis,\" \"polyphyllin,\" and \"respiratory diseases.\" Studies were selected based on relevance to respiratory disease mechanisms and pharmacological evidence. RPS and its derivatives exhibit multi-target regulatory activities across respiratory disease models, including chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), pulmonary fibrosis (PF), and lung cancer. These effects are primarily mediated through modulation of inflammation, oxidative stress, apoptosis, and key signaling pathways such as NF-κB, PI3K/AKT, MAPK, and Nrf2. Current evidence is exclusively derived from preclinical studies, including in vitro and in vivo experimental models, with no clinical data available in humans. Although RPS demonstrates promising multi-target pharmacological effects in respiratory disease models, these findings should be interpreted with caution. Further pharmacokinetic, toxicological, and clinical studies are required to evaluate its translational potential.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20199-20213"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herbacetin as a natural GPR35 agonist for allergic asthma relief via dual regulation of PI3K/Akt/mTOR and MAPK signaling.","authors":"Ziwei Zhang, Qichao Hu, Weixiang Zhao, Yaru Sun, Hanzhen Wang, Zhichao Zhou, Jinyu Qiao, Liying Shi","doi":"10.1007/s00210-026-05699-7","DOIUrl":"10.1007/s00210-026-05699-7","url":null,"abstract":"<p><p>Allergic asthma is a chronic inflammatory airway disease with complex pathogenesis and limited therapeutic options. G protein-coupled receptor 35 (GPR35) is increasingly recognized as an important regulator of immune and inflammatory responses and represents a potential therapeutic target for asthma. Herbacetin (HBN), a natural flavonoid with anti-inflammatory activity, has shown potential anti-asthmatic effects; however, its direct molecular targets and underlying mechanisms remain unclear. This study investigated whether the anti-allergic effects of HBN are mediated through GPR35 activation and explored the associated downstream signaling pathways. Agonist activity was evaluated using dynamic mass redistribution assays in CHO-K1-hGPR35 and CHO-K1-mGPR35 cells. Molecular docking and molecular dynamics simulations were employed to analyze HBN-GPR35 binding. GPR35 internalization was assessed in HT-29 cells by immunofluorescence. Changes in PI3K/Akt/mTOR and MAPK pathway phosphorylation were examined by Western blotting, with the GPR35 antagonist ML145 used for validation. The results showed that HBN acted as a potent GPR35 agonist, with EC₅₀ values of 7.45 μM for hGPR35 and 1.39 μM for mGPR35, and induced receptor internalization, which was blocked by ML145. Molecular docking revealed a strong binding affinity between HBN and GPR35 (-8.249 kcal/mol), and molecular dynamics simulations confirmed the stability of the complex. Mechanistically, HBN inhibited PI3K/Akt/mTOR phosphorylation while promoting activation of MAPK signaling pathways, including ERK, p38, and JNK; these effects were reversed by ML145. In conclusion, herbacetin functions as a GPR35 agonist and exerts anti-allergic effects in asthma through GPR35-dependent modulation of PI3K/Akt/mTOR and MAPK signaling pathways, supporting GPR35 as a promising therapeutic target for allergic asthma.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20537-20549"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mangiferin mitigates mercuric chloride-induced hepatotoxicity: targeting Nrf2, NF-κB, NLRP3, and ER stress.","authors":"Hager E Hassan, Sara H Hazem, Marwa S Zaghloul","doi":"10.1007/s00210-026-05709-8","DOIUrl":"10.1007/s00210-026-05709-8","url":null,"abstract":"<p><p>Mangiferin (Man), a xanthone glucoside, has been reported for its antioxidant, antiviral, anticancer, anti-inflammatory, and gene-regulatory properties. Mercuric chloride (HgCl₂) is a toxic inorganic heavy metal compound that induces significant hematotoxic, hepatotoxic, neurotoxic, nephrotoxic, and genotoxic effects in biological systems. Therapeutic strategies targeting HgCl₂-induced liver damage remain inadequately investigated. This study evaluated Man's protective effect against HgCl₂-induced acute liver injury and the possible molecular mechanisms of hepatic protection effects in mice. Adult male BALB/c mice were administered two doses of Man (50 and 100 mg/kg, PO) 2 h before daily injections of HgCl₂ (3 mg/kg, IP) for seven consecutive days. The results indicated Man's protective capabilities, as shown by marked improvement in hepatic histological abnormalities caused by HgCl₂, along with the normalization of blood liver enzyme levels (ALT, AST, and LDH). These protective effects can be attributed to (i) cellular oxidative balance restoration via Nrf2 activation, TAC recovery, and NO and MDA reduction; (ii) suppression of pro-inflammatory signaling (NF-κB, NLRP3, IL-1β, and Casp-1); (iii) apoptotic-proliferative homeostasis restoration via Bax downregulation and Bcl-2 upregulation; and (iv) endoplasmic reticulum stress attenuation (PERK and CHOP). In conclusion, Man could be considered as a potential protective agent against HgCl₂-induced liver injury through controlling oxidative stress, inflammation, and apoptosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21497-21508"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of differential cytotoxicity and ROS-driven severe genomic DNA damage and intrinsic mitochondrial apoptosis by erbium oxide nanoparticles in p53-compromised human NSCLC cells.","authors":"Hanan R H Mohamed, Alaa H Elsewedy, Shahd Mosaad, Aya A Osman, Habiba M Zaki, Mayada E Borai, Ayman Diab, Gehan Safwat","doi":"10.1007/s00210-026-05747-2","DOIUrl":"10.1007/s00210-026-05747-2","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with current therapeutic strategies limited by systemic toxicity, drug resistance, and poor tumor selectivity. These limitations highlight the urgent need for safer, targeted therapeutic strategies. In this context, erbium oxide nanoparticles (Er₂O₃NPs) have attracted attention in biomedical research due to their unique physicochemical characteristics, yet their potential as anticancer agents against NSCLC remains fully unexplored. This study was consequently conducted to assess the anticancer efficacy and underlying mechanisms of Er₂O₃NPs in human A549 NSCLC cells, alongside with evaluating their safety in normal WI-38 lung fibroblasts. Cytotoxicity was determined using the MTT assay, and genomic DNA integrity was assessed via the alkaline Comet assay. Oxidative stress and mitochondrial function were evaluated through 2',7'-dichlorodihydrofluorescein diacetate (2,7-DCFH-DA) and Rhodamine-123 staining, respectively. Apoptotic induction was analyzed using DAPI nuclear staining and chromatin diffusion assays, while qRT-PCR quantified the expression of apoptosis- and mitochondria-related genes. Er₂O₃NPs exhibited concentration-dependent cytotoxicity in A549 cells (IC₅₀ = 93.46 µg/ml) and lower toxicity in WI-38 fibroblasts (IC₅₀ = 147.5 µg/ml), yielding a selectivity index of 1.58. Mechanistically, treating A549 cells at the IC₅₀ concentration for 72 h induced severe genomic DNA damage, excessive ROS generation, and pronounced mitochondrial membrane depolarization. DAPI staining revealed characteristic apoptotic nuclear changes, including chromatin condensation and fragmentation, while the chromatin diffusion assay demonstrated extensive DNA dispersion indicative of advanced apoptotic DNA degradation. Moreover, qRT-PCR analysis showed significant downregulation of p53, Bcl-2, and ND3 gene expression. Given the inherent mutant p53 status of A549 cells, this transcriptional downregulation indicates that Er₂O₃NPs bypass canonical wild-type p53 transcriptional activation, triggering instead an ROS-driven intrinsic mitochondrial apoptotic signaling pathway. In conclusion, Er₂O₃NPs induce preferential cytotoxicity in NSCLC cells through ROS-mediated severe genomic DNA damage and intrinsic mitochondrial dysfunction within a p53-compromised genetic background. These findings suggest that Er₂O₃NPs hold potential as a nanotherapeutic candidate for NSCLC. However, further in vivo studies, targeted delivery systems, and direct protein-level evaluations are warranted to fully clarify these mechanisms and advance their clinical applicability.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21537-21553"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of silver-doped copper carbonate nanoparticles for antidiabetic and wound healing effects in mice.","authors":"Muhammad Zahir Tahir, Ali Umar, Waseem Ul Ghafoor, Misbah Ullah Khan, Muhammad Saleem Khan","doi":"10.1007/s00210-026-05696-w","DOIUrl":"10.1007/s00210-026-05696-w","url":null,"abstract":"<p><p>Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia and oxidative stress, leading to multi-organ dysfunction and impaired wound healing. This study evaluated the antidiabetic, antioxidant, hematological, biochemical, and wound-healing effects of silver-doped copper carbonate nanoparticles (Ag-CuCO₃ NPs) in alloxan-induced diabetic albino mice. Diabetes was induced via intraperitoneal injection of alloxan monohydrate (150 mg/kg) and animals were divided into control, diabetic control, and treatment groups receiving low dose (LD) or high dose (HD) of Ag-CuCO₃ NPs orally for 28 days. Hematological, biochemical, hormonal, electrolyte, and wound-healing parameters were assessed, and data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test, with p < 0.05 considered statistically significant. Diabetic controls showed severe hyperglycemia (> 280 mg/dL), elevated LDL (64 ± 3 mg/dL), reduced RBC count (5.1 ± 0.3 × 10⁶/µL) and delayed wound closure beyond Day 20. Low-dose Ag-CuCO₃ NP treatment significantly reduced fasting blood glucose levels from diabetic values (> 280 mg/dL) toward near-normal levels and improved hematological indices, including a ~ 42% increase in RBC count (2.85 to 4.05 × 10⁶/µL), ~ 38% increase in hemoglobin (7.46 to 10.33 g/dL), and ~ 115% increase in hematocrit (10.43 to 22.43%) compared with diabetic controls. Insulin levels increased by ~ 53% (6.12 to 9.35 µIU/mL), while sodium levels improved by ~ 3% (136.13 to 140.03 mmol/L), indicating partial restoration of metabolic and renal balance. High-dose treatment produced a more pronounced improvement in oxidative status, with SOD activity increasing by ~ 100% (2.31 to 4.62 U/mg protein) and lipid peroxidation marker MDA decreasing by ~ 51% (6.41 to 3.12 nmol/mg protein). However, high-dose treatment was also associated with elevations in hepatic enzymes, including AST (~ 50% increase; 56.33 to 84.66 U/L) and ALT (~ 114% increase; 25.66 to 55 U/L), suggesting potential dose-related hepatic stress. While high-dose treatment achieved faster glycemic and oxidative stress correction, low-dose treatment provided more balanced therapeutic efficacy with minimal biochemical disturbances. Overall, these findings provide preliminary evidence of dose-dependent antidiabetic, antioxidant and wound-healing effects of Ag-CuCO₃ nanoparticles in a preclinical diabetic model, warranting further mechanistic and comparative investigations.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20757-20777"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myrtenol modulates TWEAK/TLR4-NF-κB, miR-21, PTEN, and ERK-1 expressions and improves behavioral outcomes in a rat glioblastoma model.","authors":"Sina Delshad, Saeideh Jafarinejad-Farsangi, Mohammadreza Ghasem-Shirazi, Reza Kheirandish, Hamideh Bashiri","doi":"10.1007/s00210-026-05705-y","DOIUrl":"10.1007/s00210-026-05705-y","url":null,"abstract":"<p><p>Glioblastoma (GBM) triggers profound neuroinflammatory and oncogenic signaling that contributes to both tumor progression and behavioral disturbances. Myrtenol (MYRT), a naturally occurring monoterpene, exhibits anti-inflammatory and neuroprotective properties, but its effects on GBM-related molecular pathways remain poorly defined. This study investigated the impact of MYRT on key inflammatory and oncogenic mediators, including TWEAK, NF-κB, miR-21, PTEN, ERK-1, TLR4, and cytokine balance, alongside behavioral outcomes, in a rat model of GBM. Male Wistar rats were assigned to sham, vehicle, or MYRT (25, 50, and 100 mg/kg) groups. Behavioral alterations were assessed using the open field test (OFT). GBM induction was confirmed histopathologically using Cresyl Violet (Nissl) staining. Additionally, hematoxylin and eosin (H&E) staining was performed to examine histopathological changes in the brain tissues of the treatment groups. Gene expression of TWEAK, NF-κB, miR-21, PTEN, and ERK-1 was quantified by real-time PCR. Protein expression of TLR4 and NF-κB and the cerebral IL-1β/IL-10 ratio were assessed to evaluate neuroinflammatory status. GBM induction significantly increased anxiety-like behavior, evidenced by reduced center time, increased grooming, and decreased rearing in the OFT. These behavioral abnormalities were accompanied by marked histopathological disruption, upregulation of TWEAK, NF-κB, miR-21, ERK-1, TLR4, and NF-κB expressions, an elevated IL-1β/IL-10 ratio, and suppression of PTEN. MYRT treatment, particularly at 100 mg/kg, was associated with significant improvements in behavioral deficits, reduction of tumor burden and mitotic figures, lower levels of inflammatory and oncogenic signaling markers, and higher PTEN expression and a more balanced cytokine profile. Lower MYRT doses showed partial effects. For miR-21, a nonsignificant numerical reduction was observed at the highest MYRT dose. MYRT treatment correlates with reduced GBM-induced behavioral, inflammatory, and molecular disturbances. These observations are consistent with the modulation of interconnected inflammatory and oncogenic pathways, including TWEAK, TLR4/NF-κB, PTEN, and ERK-1, as well as with a shift towards cytokine homeostasis. The nonsignificant numerical trend in miR-21 expression warrants further investigation.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21621-21637"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tacrolimus combined with everolimus versus sirolimus in organ transplantation: a comparative pharmacovigilance analysis of the FDA Adverse Event Reporting System.","authors":"Yanlang He, Chen Luo, Shuangyan He, Sha Li, Haolin Zhou, Sheng Wei","doi":"10.1007/s00210-026-05739-2","DOIUrl":"10.1007/s00210-026-05739-2","url":null,"abstract":"&lt;p&gt;&lt;p&gt;To compare the adverse event reporting profiles of tacrolimus combined with everolimus versus tacrolimus combined with sirolimus for immunosuppressive therapy after organ transplantation using the FDA Adverse Event Reporting System (FAERS) database and to generate hypotheses to inform the individualized selection of mTOR inhibitors. As FAERS does not record drug dose, the two combinations are compared without reference to tacrolimus dosing. Adverse event reports from the FAERS database spanning the first quarter of 2004 to the fourth quarter of 2025 were extracted. Disproportionality analysis was performed using four methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). Analyses were conducted at the system organ class (SOC) and preferred term (PT) levels, as well as age-stratified (&lt; 60 years vs. ≥ 60 years), sex-stratified, and time-to-onset analyses. A total of 3101 reports for tacrolimus combined with everolimus (ta_ev) involving 13,237 adverse events, and 3093 reports for tacrolimus combined with sirolimus (ta_si) involving 13,356 adverse events were retrieved. The ta_ev regimen generated 459 PT signals covering 25 SOCs, with the three strongest SOCs being renal and urinary disorders (ROR = 4.85), infections and infestations (ROR = 3.55), and blood and lymphatic system disorders (ROR = 3.48). The ta_si regimen generated 413 PT signals also covering 25 SOCs, with the three strongest SOCs being immune system disorders (ROR = 5.22), renal and urinary disorders (ROR = 3.52), and blood and lymphatic system disorders (ROR = 2.98). Both regimens generated strong renal/urinary and haematological disproportionality signals, but the reporting patterns diverged in several respects: the ta_ev regimen had a significantly stronger signal for hepatobiliary disorders (ROR = 3.12 vs. 1.89), whereas the ta_si regimen showed a stronger signal for cardiac disorders (ROR = 1.14 vs. 0.81) and a stronger association with wound healing complications. A formal between-regimen comparison (ratio of reporting odds ratios (rROR), with 95% CIs) indicated that these differences in reporting were statistically distinguishable (Table 5), although the magnitudes were modest for the cardiac and several other classes. Age-stratified analysis indicated that patients under 60 years of age had a higher frequency and greater variety of adverse events; male patients accounted for a higher proportion of reports in both groups. The median time to adverse event onset was approximately 3-3.5 months, but more than 10% of events occurred after one year of treatment. Tacrolimus combined with everolimus and with sirolimus show distinct adverse event reporting profiles in FAERS: the everolimus-based combination was relatively enriched for hepatobiliary, BK-related renal and infectious events, and the sirolimus-based combination for cardiac, immune system, and wound ","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21355-21371"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"6-Shogaol attenuates cisplatin-induced gastrointestinal inflammation involving modulation of the putative mTOR/TFEB-mediated autophagy-lysosomal pathway.","authors":"Wenzhuo Zhang, Qingqing Liu, Chenglu Yang, Lei Feng, Yunjing He, Yujie Gao, Yusu Wang, Siyu Han, Yarong Zhai, Ke Nie","doi":"10.1007/s00210-026-05725-8","DOIUrl":"10.1007/s00210-026-05725-8","url":null,"abstract":"<p><p>Gastrointestinal (GI) inflammation is a predominant toxic side effect of cisplatin therapy in oncology patients. 6-Shogaol, among the most effective components derived from ginger, is effective in reducing inflammation, but its inhibitory effects on cisplatin-induced GI inflammation are unknown. This study investigates whether 6-shogaol control of cisplatin-induced GI inflammation is associated with the mTOR/TFEB-mediated autophagy-lysosomal pathway. GI inflammation was assessed by H&E staining and ELISA, while network pharmacology and molecular docking were employed to identify potential targets and mechanisms. Furthermore, the autophagy marker LC3 was detected by immunofluorescence, and the mTOR/TFEB pathway was evaluated by Western blot. 6-Shogaol treatment exerted therapeutic efficacy on GI inflammation via improving cisplatin-triggered reduction in body weight and ameliorated inflammatory pathological injury in mice, with decreased levels of IL-1β, IL-6, and TNF-α. Mechanistically, 6-shogaol increased LC3II/Ⅰ, CTSB, and LAMP1 protein expression; decreased p62 protein expression; and improved the autophagy-lysosomal pathway. Immunofluorescence confirmed increased LC3 expression, particularly at the high dose. Network pharmacology and molecular docking suggested that mTOR is a key putative target of 6-shogaol in the prevention and treatment of GI inflammation, and 6-shogaol treatment was associated with suppressed mTOR/TFEB phosphorylation and enhanced TFEB entry into the nucleus. These findings indicate that cisplatin-induced autophagy suppression and GI inflammation correlate with dysregulated mTOR/TFEB signaling, while 6-shogaol treatment was associated with attenuated GI injury in conjunction with modulation of the putative mTOR/TFEB-mediated autophagy-lysosomal pathway.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21245-21262"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of essential drug lists: concordance, differences, and the need for core lists in times of crisis.","authors":"Lilly Josephine Bindel, Roland Seifert","doi":"10.1007/s00210-026-05698-8","DOIUrl":"10.1007/s00210-026-05698-8","url":null,"abstract":"<p><p>The prioritization of essential drugs is important for rational pharmacotherapy, public health, drug availability, and medical education. While the Model List of Essential Medicines (EML) of the World Health Organization (WHO) is considered the international reference, other drug lists focus on supply-related or educational purposes. Seven drug lists were compared. Drug names were extracted, harmonized, and analysed for their presence on each list. Assessed were the number of listings per drug, the concordance between the lists, and the comparison of the EML 2025 with other lists. In addition, frequently prescribed drugs in Germany were compared with the summarized drug list. In total, 1061 single drugs were identified. Most drugs were listed on one to three drug lists (n = 824; 77.6%), whereas 49 drugs were listed on six or seven lists. These highly concordant drugs mainly covered broad-use symptomatic care, long-term treatment of chronic disorders, and emergency situations. Several frequently prescribed drugs and relevant indication areas were not represented within the highly concordant core. Essentiality strongly depends on the purpose, scope, and regional context of a drug list. Broad concordance can support the relevance and recognition of established drugs across different contexts, but does not prove therapeutic value or essentiality. Therefore, comparison with other drug lists provides an additional perspective, but should be combined with drug-specific assessment of therapeutic value, safety, prescription relevance, feasibility, and global need. Especially in times of crisis, effort is needed for the development of national and international core essential drug lists.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"21077-21097"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Edaravone provides neuroprotection against chronic heat stress-induced behavioral dysfunction through adaptive proteomic remodeling.","authors":"Shab M M Alkhoujah, Ruba A Zenati, Munazza Ahmed, Sana'a Jaber, Ahmad Y Abuhelwa, Shereen M Aleidi, Shirin Farheen, Amgad Albohy, Omar F Khabour, Majed M Masadeh, Zainab M AlShareef, Yasser Bustanji, Karem H Alzoubi, Mohammad H Semreen","doi":"10.1007/s00210-026-05686-y","DOIUrl":"10.1007/s00210-026-05686-y","url":null,"abstract":"<p><p>Heat stress is an increasing global health concern associated with high mortality and multi-organ dysfunction. The brain is particularly vulnerable to heat stress, which can lead to behavioral impairments. At the molecular level, heat stress disrupts proteins involved in synaptic communication, mitochondrial function, and cellular homeostasis. Current treatments are mainly symptomatic, highlighting the need for targeted neuroprotective strategies. Edaravone, a potent free-radical scavenger with anti-inflammatory properties, has demonstrated neuroprotective effects in various neurological conditions. This study aimed to evaluate the neuroprotective effects of edaravone against heat stress-induced behavioral dysfunction and to investigate the underlying molecular mechanisms using proteomic analysis. Male Wistar rats (n = 54) were assigned to four groups: control, heat stress (HS), edaravone (Edv), and heat stress plus edaravone (HS + Edv). Heat stress exposure and edaravone treatment were administered for 12 weeks. Behavioral assessments, including radial arm water maze (RAWM), open field test (OFT), elevated plus maze (EPM), and tail suspension test (TST), were conducted. Proteomic analysis of the cortex, hippocampus, and cerebellum was performed using LC-MS/MS with a nanoElute-QTOF-MS system. Heat stress impaired memory retention and increased anxiety-like behavior, while evidence for depressive-like behavior was modest. Proteomic analysis revealed region-specific alterations, with the hippocampus showing the largest number of significantly altered proteins, while the cortex showed the strongest multivariate separation between groups. The HS + Edv group showed partial normalization of behavioral outcomes and modulation of key proteomic pathways, including improved mitochondrial function, reduced oxidative stress, and preservation of synaptic and cytoskeletal integrity. These findings suggest that edaravone attenuates heat stress-induced brain dysfunction by promoting adaptive proteomic remodeling rather than complete restoration.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20843-20867"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}