Naunyn Schmiedebergs Arch. Pharmacol. [JOURNAL]
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200 papers
Alpha‑lipoic acid-loaded chitosan nanoparticles ameliorate streptozotocin‑induced diabetic liver injury via Nrf2/HO‑1 activation and TLR4/NF‑κB and JAK2/STAT1 inhibition.
Abdalla HA, Elmorsy EM, Jawad NMM … +5 more , Hosny N, Shams AS, Ayaz RA, Fawzy MS, Elshopakey GE
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42249096 · Publisher ↗
Diabetes mellitus is a chronic metabolic disorder in which persistent hyperglycemia promotes oxidative stress, inflammatory activation, and progressive liver injury. Alpha‑lipoic acid (ALA) is an endogenous and diet‑deri...
Diabetes mellitus is a chronic metabolic disorder in which persistent hyperglycemia promotes oxidative stress, inflammatory activation, and progressive liver injury. Alpha‑lipoic acid (ALA) is an endogenous and diet‑derived antioxidant with glucose‑lowering and insulin‑sensitizing actions. Still, its therapeutic efficacy is constrained by low oral bioavailability and rapid metabolism. In this context, the present study compared the hepatic pharmacodynamic effects of free ALA and ALA‑loaded chitosan nanoparticles (ALA‑CNPs) in streptozotocin (STZ)‑induced diabetic rats. Here, pharmacodynamic effects refer to the biochemical and molecular actions on hepatic tissue, including modulation of oxidative stress markers, activation of cytoprotective signaling pathways such as Nrf2/HO‑1, and inhibition of pro‑inflammatory cascades (e.g., TLR4/NF‑κB and JAK2/STAT1), which collectively contribute to hepatoprotection. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). Rats with fasting blood glucose ≥ 250 mg/dL were randomized into six groups (n = 15/group): non‑diabetic control, non‑diabetic + ALA, non‑diabetic + ALA‑CNPs, untreated diabetic, diabetic + ALA, and diabetic + ALA‑CNPs. Treatments were administered once daily for 4 weeks. STZ‑induced diabetes caused marked hyperglycemia, reduced serum insulin, dyslipidemia, increased serum alanine and aspartate aminotransferase activities, enhanced hepatic malondialdehyde, depletion of superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione, and downregulation of the Nrf2/HO‑1 pathway. These changes were accompanied by elevated hepatic tumor necrosis factor‑α, interleukin‑6, and interleukin‑1β; activation of Toll‑like receptor‑4/nuclear factor‑κB and Janus kinase‑2/signal transducer and activator of transcription‑1 signaling, and hepatocellular necrosis; vacuolation; mitochondrial swelling; and endoplasmic reticulum disorganization. Both ALA and ALA‑CNPs attenuated these metabolic, biochemical, and structural disturbances, but ALA‑CNPs produced more pronounced reductions in fasting blood glucose and improvements in lipid profile, antioxidant status, and liver histology. ALA‑CNPs also more effectively upregulated Nrf2/HO‑1 and suppressed Toll‑like receptor‑4/nuclear factor‑κB and Janus kinase‑2/signal transducer and activator of transcription‑1 activation and pro‑inflammatory cytokines. These findings indicate that nano‑encapsulation of ALA enhances its hepatoprotective pharmacological profile in diabetes‑associated liver injury by concomitantly targeting oxidative stress and inflammatory signaling cascades.
Biochanin A enhances wound healing in diabetic rats: emphasis on antioxidant, anti-inflammatory, angiogenic and pro-collagen activities.
AlGhamdi AS, Alkinani KB, Abdel-Naim AB … +1 more , Al-Abbasi FA
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42247007 · Publisher ↗
Diabetic wounds represent a serious complication, affecting ~ 25% of patients and may lead to amputation, with significant socioeconomic consequences. This study investigated the potential of biochanin A (BCA), a natural...
Diabetic wounds represent a serious complication, affecting ~ 25% of patients and may lead to amputation, with significant socioeconomic consequences. This study investigated the potential of biochanin A (BCA), a natural isoflavone, to enhance wound healing in a diabetic rat model. Diabetes was induced via streptozotocin. A full-thickness about ~ 1-cm dorsal wound was created, and animals were grouped into five groups: non-diabetic control, untreated diabetic, vehicle-treated diabetic, BCA-treated diabetic, and a positive control group. All respective treatments were applied topically once daily for 14 days. Wound closure was monitored periodically. On day 15, rats were sacrificed and tissue samples were collected for histological evaluation, immunohistochemistry, and biochemical analysis to assess oxidative stress, inflammation, angiogenesis marker, and collagen deposition. BCA treatment significantly accelerated wound contraction and improved healing rates compared to untreated diabetic controls. Histopathological examination using hematoxylin and eosin and staining by Masson's trichrome showed enhanced granulation tissue formation, re-epithelialization, and neovascularization. Mechanistically, BCA activated Nrf2 and NAD(P)H:NQO1, upregulated key antioxidant enzymes SOD and CAT, and reduced lipid peroxidation accumulation. It also suppressed immune-expression of pro-inflammatory markers. Furthermore, BCA treatment enhanced expression of critical angiogenic growth factors VEGF-A and PDGFR and enhanced collagen deposition as evidenced by increased immune-expression of TGF-β1 and mRNA expression of Col1A1. Our findings demonstrate that BCA promotes diabetic wound healing through a multi-targeted mechanism involving enhancement of the antioxidant system, attenuation of the inflammatory phase, and stimulation of angiogenesis and collagen deposition.
Quercetin-conjugated nanoparticles enhance drug delivery to dental tissues: an experimental study in rats.
Esmaeili A, Feizi G, Nejatidanesh F … +1 more , Esmaeili A
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42247006 · Publisher ↗
This study investigated the potential of quercetin-conjugated superparamagnetic iron oxide nanoparticles (QC-SPIONs) as novel drug delivery systems, with a specific focus on their distribution in the dental tissues of ra...
This study investigated the potential of quercetin-conjugated superparamagnetic iron oxide nanoparticles (QC-SPIONs) as novel drug delivery systems, with a specific focus on their distribution in the dental tissues of rats. Quercetin, an antioxidant flavonoid, is limited due to its poor solubility and bioavailability, which restricts its therapeutic efficacy. To address this, 42 male Wistar rats were divided into seven groups and subjected to either oral or intraperitoneal administration of free quercetin, SPION, or QC-SPION over 35 days. The presence of iron and quercetin in the tooth tissue was assessed via inductively coupled plasma (ICP) spectroscopy and high-performance liquid chromatography (HPLC), respectively. Biochemical markers of the liver and kidney function were assessed to evaluate systemic safety, while real-time PCR was performed to assess the expression levels of apoptotic genes mRNA (Bax and Bcl-2) in tooth pulp. The results demonstrated that intraperitoneal administration of QC-SPIONs significantly enhanced quercetin and iron concentrations in dental tissues compared to oral administration, indicating superior tissue penetration. Importantly, no adverse effects on liver (AST, ALT, ALP, GGT, LDH) or kidney (GGT, LDH) function were observed, and there were no significant changes in apoptotic gene expression, suggesting the absence of systemic toxicity or cellular apoptosis. These findings highlight the potential of QC-SPIONs as a safe and effective strategy for targeted oral drug delivery, offering improved quercetin biodistribution in dental tissues without inducing adverse effects. This approach could pave the way for innovative treatments addressing oxidative stress-related oral diseases.
Post-marketing safety profile of palivizumab: a 20-year pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS).
Yan Q, Zhong Y
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42240666 · Publisher ↗
Palivizumab is an FDA-approved monoclonal antibody for preventing severe respiratory syncytial virus (RSV) infections in high-risk children. However, its real-world safety profile, particularly beyond clinical trial popu...
Palivizumab is an FDA-approved monoclonal antibody for preventing severe respiratory syncytial virus (RSV) infections in high-risk children. However, its real-world safety profile, particularly beyond clinical trial populations, remains incompletely characterized. This study aimed to systematically analyze adverse events (AEs) associated with palivizumab using two decades of data from the FDA Adverse Event Reporting System (FAERS) to identify known, novel, and rare safety signals. This study aimed to characterize the post-marketing safety profile of palivizumab and identify AE signals using 20 years of FDA Adverse Event Reporting System (FAERS) data. A retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q2 2024. Duplicate reports were removed, and palivizumab-related AE reports (primary suspected drug) were extracted. AEs were standardized via MedDRA v27.0 and categorized by system organ classes (SOCs) and preferred terms (PTs). Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN), were used to detect signals, with predefined criteria for signal validation. Among 21,558,936 total FAERS reports, 14,120 (0.065%) palivizumab-related AE cases were included, predominantly in infants aged 28 days-23 months (45.92% of all cases); 51.74% of cases with known sex were male. The most frequent serious outcome was hospitalization (60.98%), followed by death (12.12%). Three system organ class-level positive signals were identified, including two novel signals (Infections and infestations; Congenital, familial and genetic disorders). The strongest preferred term-level positive signals were RSV-related events, with novel signals including infantile spitting up, post-tussive vomiting, oligodipsia, and Kawasaki's disease. This 20-year real-world study confirms known AEs of palivizumab and identifies novel signals, particularly in infection-related and congenital disorder categories. These findings do not establish causality but highlight the need for prospective studies to validate associations, guiding safer clinical use in high-risk pediatric populations.
Development and validation of a prognostic nomogram for predicting the progression risk of HCC after lenvatinib therapy.
Xie C, Luo S, Lin S … +3 more , Huang X, Weng X, Xu X
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42240665 · Publisher ↗
Although lenvatinib presents promising results in advanced hepatocellular carcinoma (HCC), the treatment responses have distinct individual variability. To address this, we aimed to construct a prognostic model to foreca...
Although lenvatinib presents promising results in advanced hepatocellular carcinoma (HCC), the treatment responses have distinct individual variability. To address this, we aimed to construct a prognostic model to forecast the risk of progression in HCC patients who underwent lenvatinib therapy. Accordingly, two hundred twenty-three HCC patients who received lenvatinib treatment at the First Affiliated Hospital of Fujian Medical University were enrolled. Statistically significant parameters were identified by univariate analysis and multivariate Cox regression analysis. Subsequently, receiver operating curves (ROC) and calibration curves were plotted to estimate the predictive accuracy and discriminative ability of the model. Decision curve analysis (DCA) was carried out to assess the clinical utility of the nomogram by quantifying the net benefits under all threshold probabilities, and the bootstrap re-sampling method was chosen for the internal validation. Finally, tumor number, tumor size, metastasis, alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA-II) and Child-Pugh grade were finally included in the nomogram to predict the 6-, 12- and 18- months progression-free survival (PFS) rates of lenvatinib-treated HCC patients. An unadjusted C-index of 0.725 and a bootstrap-corrected C-index of 0.689 indicated good prediction accuracy of the model. The AUC for 6-, 12- and 18-month PFS rates were 0.663, 0.677 and 0.810 repetitively. The calibration curve showed that there was a good agreement between predicted progression probability and actual observation one, and DCA indicated a favorable clinical benefit of the nomogram. In summary, Aa practical and well-calibrated model was developed, which could objectively predict the prognosis of lenvatinib treatment in HCC patients.
Clinical characteristics and treatment of low-dose methotrexate-related adverse reactions in rheumatoid arthritis: a retrospective study.
Liu R, Xing Q, Liu Z … +4 more , Li W, Chen K, Li R, Liu X
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42240664 · Publisher ↗
Low-dose methotrexate (MTX) (5-25 mg/week) is widely used in the treatment of autoimmune diseases and is considered relatively safe. There have been reports of toxicities caused by MTX, but the characteristics remain unc...
Low-dose methotrexate (MTX) (5-25 mg/week) is widely used in the treatment of autoimmune diseases and is considered relatively safe. There have been reports of toxicities caused by MTX, but the characteristics remain unclear. Through a retrospective case series at our hospital, we describe the clinical features, management, and outcomes of adverse reactions caused by MTX. This is a retrospective, single-center case series of patients with rheumatoid arthritis (RA) who developed adverse reactions while receiving low-dose MTX (5-25 mg/week) between March 2022 and August 2025. Exclusion criteria included adverse reactions due to other drugs, viral infections, or vitamin B12/folate deficiency. We present only descriptive statistics (median, range, frequency). The series included 18 patients. Of these, 77.78% were female. Median age was 72 years (51-77 years). Median MTX dosage was 10 mg (7.5-35 mg) weekly. Adverse reactions involved multiple organ systems. Hematological adverse reactions were primarily characterized by cytopenia, anemia, and bleeding. Gastrointestinal adverse reactions were nausea and vomiting. Skin-related adverse reactions included skin ulcers, erythema, swelling, and pain. Leucovorin calcium rescue therapy via intravenous administration was given in 77.78% of patients. Additionally, 9 patients (50.00%) required blood transfusion, 8 patients (44.44%) received recombinant human granulocyte-stimulating factor, and 5 patients (27.78%) were treated with sodium bicarbonate for urine alkalization. During hospitalization, 2 patients (11.11%) died, both due to severe infectious complications. Most adverse reactions caused by low-dose MTX were manageable with supportive care. However, severe toxicity (including fatalities) occurred in elderly or frail patients. Serum MTX concentration showed inconsistent associations with adverse reactions and should not be relied upon to predict low-dose MTX toxicity.
DDIT4 silencing attenuates sevoflurane-induced ferroptosis via the mTOR pathway in neuronal cells.
Yu S, Xi M, Chen J … +2 more , Yang H, Xu Z
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42240663 · Publisher ↗
DNA damage-inducible transcript 4 (DDIT4) participates in neuronal cell ferroptosis and can be upregulated by sevoflurane (Sev). This study aimed to explore whether silent DDIT4 can improve Sev-induced neuronal cell ferr...
DNA damage-inducible transcript 4 (DDIT4) participates in neuronal cell ferroptosis and can be upregulated by sevoflurane (Sev). This study aimed to explore whether silent DDIT4 can improve Sev-induced neuronal cell ferroptosis and its potential mechanism. HT22 and SH‑SY5Y cells were transfected with siDDIT4 and exposed to Sev with or without the mammalian target of rapamycin (mTOR) inhibitor rapamycin. In both HT22 and SH-SY5Y cells, Sev exposure increased DDIT4, promoted ferroptosis, and inhibited the mTOR pathway (all P < 0.05). DDIT4 knockdown improved HT22 and SH-SY5Y cell viability (both P < 0.05), reduced reactive oxygen species (ROS) (both P < 0.05), malondialdehyde (MDA) (both P < 0.05), and Fe accumulation (both P < 0.01), while increasing glutathione peroxidase 4 (GPX4) (both P < 0.05). DDIT4 knockdown also elevated solute carrier family 7-member 11 (SLC7A11) expression in HT22 cells (P < 0.05). Additionally, DDIT4 knockdown activated the mTOR pathway in HT22 and SH-SY5Y cells (both P < 0.05). Notably, the addition of rapamycin abolished the protective effect of DDIT4 knockdown on Sev-induced ferroptosis in HT22 and SH-SY5Y cells (all P < 0.05). DDIT4 knockdown alleviates Sev-induced ferroptosis in neuronal cells by activating the mTOR pathway. The findings of this study support the possibility of DDIT4 as a therapeutic target for Sev-related neurotoxicity.
Calcium hydroxide nanoparticles-induced oxidative stress and mitochondrial impairment drive genomic instability and programmed cell death in colorectal cancer cells.
Mohamed HRH, Hekal RS, Fahmy CWH … +5 more , Elhaggan SO, Noure Z, Ahmed N, Diab A, Safwat G
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42240662 · Publisher ↗
The high aggressiveness, metastatic potential, and mortality of colorectal cancer, together with the limitations of conventional chemotherapy, highlight the urgent need for safer and more effective therapeutic alternativ...
The high aggressiveness, metastatic potential, and mortality of colorectal cancer, together with the limitations of conventional chemotherapy, highlight the urgent need for safer and more effective therapeutic alternatives. Nanotherapies offer promising advantages through improved bioavailability and tumor targeting. In particular, calcium hydroxide nanoparticles (Ca(OH)NPs) possess unique physicochemical properties, yet their anticancer potential in colorectal cancer remains fully unexplored. This study was consequently undertaken to estimate the cytotoxic effects and underlying molecular mechanisms of Ca(OH)NPs in human colorectal HCT-116 cancer cells, while also exploring their impact on the viability of normal human HFB4 melanocytes. Normal HFB4 and cancerous HCT-116 cells were exposed to serial two-fold concentrations of Ca(OH)NPs ranging from 7.80 to 1000 mg/ml for 72 h, and cell viability was assessed using the MTT assay. Intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential were measured using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and rhodamine-123 staining, respectively. Genomic DNA damage was evaluated by the alkaline comet assay, whereas apoptosis induction was analyzed using DAPI staining and the chromatin diffusion assay. The expression levels of mitochondria- and apoptosis-related genes were quantified by quantitative real-time PCR (qRT-PCR). Results of the MTT assay demonstrated that Ca(OH)NPs exerted significant, dose-dependent cytotoxicity on colorectal HCT-116 cancer cells, as evidenced by a markedly low IC50 value of 35.04 µg/ml and a substantial reduction in cell viability. In contrast, the viability of normal HFB4 melanocytes was only slightly affected, and only at the highest Ca(OH)NPs concentration tested, as indicated by a comparatively high IC50 value of 190.80 µg/ml. The resulting selectivity index of 5.44 further supports the notable cytotoxicity of Ca(OH)NPs toward HCT-116 colorectal cancer cells. Furthermore, treatment of HCT-116 cells with Ca(OH)NPs at the IC50 concentration (35.04 µg/ml) led to a significant increase in intracellular ROS generation level, dramatic loss of mitochondrial membrane potential, and pronounced oxidative DNA damage, ultimately culminating in apoptotic cell death. qRT-PCR analysis also demonstrated significant downregulation of both the apoptotic p53 and the anti-apoptotic Bcl-2 gene expression, alongside significant upregulation of the mitochondrial ND3 gene expression. These molecular alterations support the involvement of mitochondrial dysfunction and apoptosis-related gene modulation in the observed Ca(OH)NPs-induced cytotoxic effects. Conclusion: Ca(OH)NPs demonstrate notable anticancer activity against human colorectal HCT-116 cancer cells, primarily through ROS-mediated oxidative stress, genomic DNA damage, mitochondrial dysfunction, and apoptosis induction. These findings highlight Ca(OH)NPs as a potent nanotherapeutic candidate for colorectal cancer management. However, the current study was limited to in vitro experimental conditions, and the precise molecular mechanisms underlying these effects remain incompletely understood. Therefore, further mechanistic investigations, advanced in vitro and in vivo studies, and comprehensive biocompatibility and safety evaluations are required to validate their therapeutic potential and clinical applicability.
The current status and influencing factors of prophylactic antibacterial drug use in patients with hypertriglyceridemic acute pancreatitis.
Xie P, Jiao S, Liu J … +6 more , Xie J, Wang Y, Zhang Y, Lu L, Guo Y, Bai P
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42234121 · Publisher ↗
The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) is increasing, while inappropriate antimicrobial use remains a major concern. This study aimed to evaluate current antimicrobial prescribing patterns in H...
The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) is increasing, while inappropriate antimicrobial use remains a major concern. This study aimed to evaluate current antimicrobial prescribing patterns in HTG-AP patients and identify factors influencing their use. We retrospectively analyzed the clinical data of 154 hospitalized patients with HTG-AP. According to whether antimicrobial therapy was administered, patients were divided into an antibacterial drug group and a non-antibacterial drug group. Multivariable logistic regression was performed to identify independent predictors of antimicrobial use, and receiver operating characteristic (ROC) curves were constructed to assess predictive performance. Logistic regression analysis revealed that admission to the surgical department (OR = 4.950, 95% CI = 1.180-20.690), treatment at medical institutions in Ulanqab (OR = 13.801, 95% CI = 3.161-61.539) or Xing'an Alliance (OR = 16.280, 95% CI = 3.759-69.858), and elevated white blood cell count (OR = 1.291, 95% CI = 1.061-1.561) were independent risk factors for antimicrobial use. Conversely, a higher lymphocyte ratio was independently associated with lower antibacterial drug use (OR = 0.947, 95% CI = 0.909-0.989). The predictive model incorporating these variables demonstrated good discrimination, with an AUC of 0.886. In conclusion, antimicrobial use in HTG-AP patients remains high, with evidence of inappropriate prescribing. Strengthened antimicrobial stewardship is warranted to promote rational therapy.
Low plasma edoxaban concentrations during therapeutic drug monitoring: a single-center retrospective study.
Flis P, Chaireti R, Malmström RE … +1 more , Nowinski K
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42234120 · Publisher ↗
In our therapeutic drug monitoring (TDM) laboratory, over one-third of approximately 350 analyzed samples from patients on edoxaban were < 12 ng/mL, which is below concentrations reported in clinical trials. Our study ai...
In our therapeutic drug monitoring (TDM) laboratory, over one-third of approximately 350 analyzed samples from patients on edoxaban were < 12 ng/mL, which is below concentrations reported in clinical trials. Our study aimed to explore the effect of factors potentially associated with low edoxaban concentrations in patients monitored with TDM. A retrospective cohort study of previously analyzed edoxaban plasma concentrations collected at Karolinska University Hospital between November 2017 and May 2023 was performed. Low concentration was defined as < 12 ng/mL (30 mg) and < 16 ng/mL (60 mg). Fifty samples from 34 individuals were included. No significant difference in trough concentration between 30 and 60 mg dose group was found. Low concentrations were observed in 42% of samples. Higher estimated glomerular filtration rate (eGFR) was found among patients with low edoxaban concentrations (p = 0.004); however, the correlation between eGFR and concentration was weak (rho = - 0.4; p < 0.05). Off-label dose reduction (n = 4) and drug-drug interactions (DDIs) (n = 4) were found in cases with low concentrations. In a TDM-setting, low trough concentrations of edoxaban were frequently observed. Potential explanations include normal renal function, drug-drug interactions, and off-label dose reductions. These findings suggest that TDM may be beneficial in selected clinical scenarios. However, the study is limited by its small sample size and selected study population.
Rapid quantification method of pharmaceuticals in urban wastewater using UHPLC-Orbitrap mass spectrometry-a multi-target approach for EU-directive advanced treatment evaluation.
Hofmann U, Oertel R, Engel N … +4 more , Zander J, Lippert A, Schubert S, Renner B
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42234119 · Publisher ↗
Pharmaceutical residues have become micropollutants of emerging concern in wastewater. Insufficient removal by wastewater treatment plants (WWTPs) can result in negative ecotoxicological impacts on aquatic ecosystems. Th...
Pharmaceutical residues have become micropollutants of emerging concern in wastewater. Insufficient removal by wastewater treatment plants (WWTPs) can result in negative ecotoxicological impacts on aquatic ecosystems. Therefore, the EU Urban Wastewater Treatment Directive (UWWTD 2024/3019) requires quaternary treatment upgrades and regular monitoring in European wastewater treatment plants. This necessitates efficient and easy-to-implement wastewater analysis methods. Consequently, this study presents a novel, sensitive, and reliable HRMS-based method for the simultaneous determination of twelve indicator substances (nine UWWTD-listed and three substitutes) in WWTP influent and effluent. The method is based on solid-phase extraction (SPE) of 2 mL wastewater samples, followed by reversed-phase ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) employing an Orbitrap Exploris™ 240. Detection was carried out using heated electrospray ionisation in positive ionisation mode (HESI+), except for diclofenac (HESI-). Quantification was performed using highly sensitive SIM scans, while high-resolution full-scan spectra were acquired for confirmation. Limits of quantification (LOQ) ranged mostly between 15 and 30 ng/L, except for candesartan, irbesartan, and diclofenac with LOQ > 50 ng/L. A laboratory validation demonstrated high precision and accuracy for all selected pharmaceuticals. Furthermore, the method was successfully applied to raw and treated wastewater from wastewater treatment plants (WWTPs) in the Saxon-Czech border region, which differ in terms of wastewater throughput and population equivalents. As a result, this method offers a rapid quantification approach for assessing the removal efficiency of pharmaceuticals and potential substitutes categorised in the UWWTD.
Injectable sericin/gelatin hydrogel enables sustained BDNF delivery and promotes neural repair under hemorrhagic injury conditions.
Gu Z, Xia J, Yang Z … +4 more , Song D, Guo J, Chen Y, Tu C
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42234118 · Publisher ↗
Cerebral hemorrhage is an acute type of stroke with a high mortality rate and very limited options for treatment because of extensive damage to the neurons and the inability of neurons to repair themselves. In this study...
Cerebral hemorrhage is an acute type of stroke with a high mortality rate and very limited options for treatment because of extensive damage to the neurons and the inability of neurons to repair themselves. In this study, we developed a new injectable hydrogel using sericin and gelatin for controlled release of brain-derived neurotrophic factor (BDNF), and we assessed how the hydrogel can provide neuroprotection and promote neuroregeneration after a brain hemorrhage. The hydrogel was made using a self-assembly method with no chemical crosslinking agents, which makes the hydrogel very compatible with tissue and capable of being injected. Characterization of the physicochemical properties of the hydrogel revealed that adding the sericin improved hydrogel stability, decreased pore size, allowing for better BDNF encapsulation, and significantly controlled the release of BDNF for at least 7 days. A SH-SY5Y cell injury model using hemin-induced cell death showed BDNF loaded inside the hydrogel improved cell viability, increased cell colony formation and migration, decreased oxidative stress, and decreased apoptosis compared to both free BDNF and blank hydrogel. Additionally, the hydrogel-treated cells had significantly greater outgrowth of neuronal processes and greater expression of neuronal markers such as βIII-tubulin and GAP43 compared to the other treatment groups. The mechanism by which the hydrogel treated the cells was through activation of TrkB signaling and downstream signaling through both the PI3K/Akt and MAPK/ERK pathways as demonstrated by Western blotting and pharmacological inhibition. BDNF released from the hydrogel maintained its biological activity and produced long-lasting therapeutic effect(s). The BDNF delivery and repair of neural tissue for the treatment of cerebrovascular diseases using injectable sericin/gelatin hydrogels are successfully accomplished by this study.
Bioequivalence study of Prontogest 100 mg/2 mL solution for intramuscular injection versus reference progesterone injection, USP 500 mg/10 mL under fasting conditions: a randomized, open-label, two-sequence, four-period, fully replicated crossover study in healthy postmenopausal women.
Habib YH, Salah M, Galal E … +6 more , Gouda A, Mosaad Y, Ali M, Mahmoud A, Habib N, Morsi M
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42228061 · Publisher ↗
Intramuscular progesterone remains an important formulation when prolonged systemic exposure is needed in gynecology and reproductive medicine. Demonstrating bioequivalence between a generic product and the reference for...
Intramuscular progesterone remains an important formulation when prolonged systemic exposure is needed in gynecology and reproductive medicine. Demonstrating bioequivalence between a generic product and the reference formulation is necessary to support therapeutic interchangeability. The objectiveof thisstudy is to compare the pharmacokinetics, bioequivalence, safety, and tolerability of Prontogest 100 mg/2 mL intramuscular injection with the reference progesterone injection after a single dose under fasting conditions. In this open-label, randomized, single-dose, two-treatment, two-sequence, four-period fully replicated crossover study, healthy postmenopausal women received the test or reference product according to TRTR or RTRT sequences, separated by 15-day washout periods. Blood samples were collected up to 72 h after each dose, and plasma progesterone concentrations were measured using a validated LC-MS/MS method. The primary pharmacokinetic endpoints were baseline-corrected C and AUC0-t, analyzed on the log-transformed scale by ANOVA. Because the within-reference variability for C was 20.84%, conventional average bioequivalence criteria were applied. Of 42 screened participants, 26 were randomized and dosed, 23 completed all four periods, and 24 were included in the pharmacokinetic/statistical analysis. Mean test and reference values were comparable for C (44.39 vs 45.33 ng/mL), AUC0-t (1030.34 vs 1028.52 ng·h/mL), and AUC0-∞ (1109.65 vs 1194.29 ng·h/mL), with identical median Tmax values of 8.3 h. The geometric mean ratio (test/reference) was 94.85% for C and 99.98% for AUC0-t, with both 90% confidence intervals falling within the accepted 80.00-125.00% bioequivalence range. Eleven mild treatment-emergent adverse events occurred in 9 participants, mainly headache, with no serious adverse events or clinically significant abnormalities. Prontogest 100 mg/2 mL was demonstrated to be bioequivalent to the reference progesterone injection after a single intramuscular dose in healthy postmenopausal women and was generally well tolerated. Registration no. in (Clinicaltrials.gov): NCT07495007.
Correction to: Integrating transcriptomics, network pharmacology, and GraphBAN neural networks to identify biomarkers and regulatory mechanisms of classical traditional Chinese medicine formulations in ulcerative colitis.
Yang Z, Lu H, Xu S … +2 more , Xiao G, Hu X
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42219408 · Publisher ↗
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Use selenium-doped TiO2 single-wall carbon nanotubes as promoter of biochemical indices in Solanum lycopersicum L. under bacterial wilt stress conditions.
Kamal A, Munir A, Khan KH … +5 more , Ara U, Hossain SKS, Otaru AJ, Amin MT, Khan H
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42219407 · Publisher ↗
The development of efficient and sustainable antibacterial agents is crucial to address the growing threat of multidrug-resistant pathogens. In this study, we report the synthesis and characterization of a novel nanocomp...
The development of efficient and sustainable antibacterial agents is crucial to address the growing threat of multidrug-resistant pathogens. In this study, we report the synthesis and characterization of a novel nanocomposite selenium-doped titanium dioxide supported on functionalized carbon nanotubes (Se-TiO@CNTs) with enhanced photocatalytic antibacterial performance under visible light. This new material was synthesized through the sol-gel method by in situ Se-TiO@CNTs nanocomposite decoration to achieve uniform dispersion and strong interfacial coupling between the components. Comprehensive characterization using XRD, TEM, SEM-EDS, FTIR, and UV-vis DLS confirmed successful Se doping of TiO and improved optical absorption in the visible range. The photocatalytic antibacterial activity was evaluated against Escherichia coli 90% and Ralstonia solanacearum, demonstrating the concentrations of 0.1 mg 82.98% bacterial inactivation within 24 h of visible-light irradiation. Mechanistic investigations revealed that the synergistic effects of Se doping facilitated efficient charge separation, suppressed electron-hole recombination, and boosted reactive oxygen species (ROS) generation, particularly •OH and •O radicals, leading to oxidative leakage of bacterial cell membranes and intracellular organelles. This work presents novel perspectives on the design of multifunctional modified Se-TiO@CNTs nanocomposites exhibiting strong antibacterial activity against both animal and plant pathogenic bacteria. Specifically, it effectively inhibits E. coli (a representative animal pathogen) and Ralstonia solanacearum (a destructive plant pathogen), highlighting its potential as a dual-purpose antimicrobial agent in both medical and agricultural applications. These modified CNTs have limited applications in agriculture. We have synthesized these modified CNTs and applied them in both medical and agricultural applications.
AI hallucinations in academic writing: implications for research integrity.
Giray L, Islam ME, Glo JA
Naunyn Schmiedebergs Arch Pharmacol · 2026 May · PMID 42217043 · Publisher ↗
As artificial intelligence becomes deeply embedded in scholarly practice, a critical and underexamined threat to research integrity has emerged: AI hallucinations. AI hallucinations refer to outputs generated by large la...
As artificial intelligence becomes deeply embedded in scholarly practice, a critical and underexamined threat to research integrity has emerged: AI hallucinations. AI hallucinations refer to outputs generated by large language models that are factually incorrect, fabricated, or logically inconsistent with verifiable knowledge, produced not through genuine understanding but through statistical pattern prediction. This paper examines how these hallucinations manifest in academic writing and analyzes their specific consequences for scholarly work. The paper identifies the principal causes of hallucination, including training data gaps, monofacts, named entity errors, and prompt design failures, and documents their most common forms in academic contexts, among them citation fabrication, factual distortion, logical inconsistency, and propagation errors. The paper then examines how these failures undermine the accuracy and reliability of research and disrupt peer review processes in ways that traditional editorial mechanisms are not equipped to detect. Ethical dimensions are addressed directly: AI hallucinations create conditions of distributed epistemic responsibility that complicate established definitions of research misconduct and authorship, yet accountability remains fully with human authors. Also, it discusses mitigation strategies, including detection tools, institutional policy frameworks, and AI literacy curricula, arguing that human verification is irreplaceable and that literacy-based approaches offer the most sustainable institutional response. Equity concerns are highlighted throughout, as hallucination rates vary by language and disciplinary domain. The paper concludes that responsible AI use in scholarship requires transparency, systematic verification, and human oversight as non-negotiable ethical obligations.
Untangling neuropathic pain: pathophysiological insights and future directions for targeted therapy.
Verma R, Singh N, Deol PK
Naunyn Schmiedebergs Arch Pharmacol · 2026 May · PMID 42217042 · Publisher ↗
The primary objective of this study is to investigate the intricate underlying mechanisms of neuropathic pain using a multifaceted framework which includes cellular, molecular, and systems-level perspectives as well as m...
The primary objective of this study is to investigate the intricate underlying mechanisms of neuropathic pain using a multifaceted framework which includes cellular, molecular, and systems-level perspectives as well as molecular targets for establishing the customised pain relief strategies to improve clinical outcomes. In order to provide an in-depth understanding of neuropathic pain processes as well as treatment approaches, this review addresses research in molecular biology, neurophysiology and molecular mechanisms including neurotransmitter modifications, ion channel failure, and gene expression changes along with current developments in emerging pharmacological and non-pharmacological therapies, relying on peer-reviewed studies, experimental research, and clinical trials. The review reveals that neuropathic pain is driven by several distinct pathways rather than a single pathological process. Significant findings demonstrate that altered ion channel activity, neurotransmitter dysregulation, inflammation, microglial activation and oxidative stress contribute to pain persistence. Current treatments, including antidepressants and opioids, provide limited relief and can cause side effects, whereas non-pharmacological methods offer supportive advantages. Neuropathic pain is a complex condition influenced by neurobiological changes at molecular, cellular, and systemic levels. Understanding of these pathways is essential for creating personalised medicines that go beyond conventional symptomatic relief. Enhancing pain management and improving patient quality of life may be possible with new molecular targets and integrated therapy approaches. In order to reduce the worldwide burden of chronic neuropathic pain, future research must concentrate on transforming molecular findings into practicable therapeutic approaches.
PIM1-mediated signalling as a therapeutic target in breast cancer: repurposing venetoclax for targeted inhibition.
Choudhury S, Kandasamy T, Ghosh SS
Naunyn Schmiedebergs Arch Pharmacol · 2026 May · PMID 42217041 · Publisher ↗
PIM1 kinase has emerged as a critical mediator of cancer progression, particularly in triple-negative breast cancer (TNBC), due to its involvement in epithelial-mesenchymal transition (EMT), drug resistance, and cell sur...
PIM1 kinase has emerged as a critical mediator of cancer progression, particularly in triple-negative breast cancer (TNBC), due to its involvement in epithelial-mesenchymal transition (EMT), drug resistance, and cell survival pathways. This study aimed to evaluate PIM1-mediated signalling as a therapeutic target in breast cancer and identify potential repurposed drugs using an integrative in silico and in vitro approach. Protein-protein interaction and pathway enrichment analyses revealed that PIM1 and its interactors are involved in EMT, cell cycle, and drug resistance pathways. Gene expression analysis using Human Protein Atlas data and qRT-PCR confirmed significantly elevated PIM1 expression in MDA-MB-231 (31.4-fold) and EMT-induced MDA-MB-231 (47.69-fold) compared to MCF-7. Structure-based virtual screening of 2,450 FDA-approved drugs and MD simulation identified Venetoclax as a potential inhibitor of PIM1, showing strong binding energy (-206.703 kJ/mol). Further, cytotoxicity assays exhibited a significantly lower IC₅₀ of Venetoclax in EMT-MDA-MB-231 cells (4.41 µM), compared to MDA-MB-231 (42.29 µM) and MCF-7 (19.68 µM). Subsequent western blot analysis showed a 2.39-fold reduction in GSK3β phosphorylation in EMT-MDA-MB-231 cells, validating inhibition of PIM1-mediated signalling. In addition, Mitoxantrone accumulation assay revealed a 1.4-fold increase, suggesting reduced ABCG2-mediated drug efflux. These findings support Venetoclax as a promising inhibitor of PIM1-mediated signalling with selective efficacy against aggressive breast cancer phenotypes. Its dual targeting of EMT signalling and drug resistance highlights its translational potential and paves the way for further clinical development.
Basal release of 6-cyanodopamine from rabbit isolated aorta and its modulation of vascular reactivity.
Dos Santos EX, Ali K, Britto-Júnior J … +10 more , Peterson L, Morris JJL, Miller A, Jacintho FF, Moraes ME, Santagada V, Caliendo G, Severino B, Antunes E, De Nucci G
Naunyn Schmiedebergs Arch Pharmacol · 2026 May · PMID 42217040 · Publisher ↗
6-Cyanodopamine (6-CYD) is a recently identified endogenous catecholamine that exerts positive chronotropic and inotropic actions, but its occurrence in vascular tissue and effects on vascular reactivity are unknown. In...
6-Cyanodopamine (6-CYD) is a recently identified endogenous catecholamine that exerts positive chronotropic and inotropic actions, but its occurrence in vascular tissue and effects on vascular reactivity are unknown. In endothelium-intact and endothelium-denuded rabbit isolated aortic rings, we investigated the basal release of 6-CYD and its effects on aortic smooth muscle reactivity. 6-Cyanodopamine release was quantified by LC-MS/MS. Isometric tension was recorded to assess concentration-response curves to noradrenaline, adrenaline, and dopamine in aortic rings pre-incubated or not with 6-CYD, whereas vasorelaxation was evaluated in endothelin-1 (ET-1)-pre-contracted rings. Rabbit aorta released significant amounts of 6-CYD, which were largely reduced either by endothelium removal or pre-incubation with the NOX1/4 inhibitor GKT137831 (1 µM), whereas the nitric oxide (NO) synthase inhibitor L-NAME (100 µM) and the voltage-gated sodium channel blocker tetrodotoxin (TTX, 1 µM) had no significant effect. Addition of 6-CYD (0.1 pM to 10 nM) had no contractile activity itself, but it significantly potentiated noradrenaline- and adrenaline-induced aortic contractions, an effect largely reduced by endothelium removal. The dopamine-induced aortic contractions remained unaffected by 6-CYD. In ET-1-pre-contracted rings, 6-CYD (1 nM-10 µM) produced concentration-dependent relaxations that were significantly reduced by endothelium removal and L-NAME (100 µM), as well as by the soluble guanylyl cyclase (sGC) inhibitors ODQ (100 µM) and methylene blue (10 µM). In conclusion, these findings identify vascular endothelium as a source of 6-CYD and indicate this catecholamine as a novel endogenous modulator of vascular tone, acting through a dual mechanism, namely, potentiating vasoconstriction and producing NO/sGC-dependent vasorelaxation.
Label-free cell phenotypic profiling of sphingosine-1-phosphate receptor 1 and discovery of its agonist from natural products.
Wang X, Sun Y, Tang H … +11 more , Hou T, Zhou H, Xie X, Li Y, Wang P, Han Y, Wei L, Xu F, Liu Y, Wang J, Wang A
Naunyn Schmiedebergs Arch Pharmacol · 2026 May · PMID 42209736 · Publisher ↗
Sphingosine-1-phosphate receptor 1 (S1PR1) belonging to G protein-coupled receptors (GPCRs), plays a significant role in autoimmune diseases and cancer via regulating immune cell migration, vascular barrier function, and...
Sphingosine-1-phosphate receptor 1 (S1PR1) belonging to G protein-coupled receptors (GPCRs), plays a significant role in autoimmune diseases and cancer via regulating immune cell migration, vascular barrier function, and cell survival. Although four S1PR1 agonists have been clinically approved, their applications are limited by adverse effects, necessitating the discovery of novel S1PR1 agonists. In this study, we established a HEK293T-hS1PR1 high-throughput screening model for S1PR1 ligand discovery using dynamic mass redistribution (DMR) and fluorescent imaging plate reader (FLIPR) assays. Through structure-based virtual screening of anti-inflammatory compounds, we identified corylin, a natural compound derived from Psoralea corylifolia L., as a novel S1PR1 agonist. Corylin demonstrated micromolar-level agonistic activity with EC values of 7.50 μM (95% CI: 6.46-8.75 μM) in DMR assay and 5.99 μM (95% CI: 2.16-16.64 μM) in FLIPR assay. Notably, corylin showed no activity against two other GPCRs (GPR84 and GPR120) commonly co-expressed with S1PR1 in immune cells. Molecular docking indicated that corylin interacted with S1PR1 via hydrophobic interaction, lacking of π-stacking with Trp269, a key interaction for SEW2871. Subsequent 500-ns molecular dynamics simulations revealed a ligand reorientation and the formation of a π-π interaction with Trp269, observed with ~ 50% occupancy, thereby demonstrating the stable binding of corylin to S1PR1. Furthermore, pathway deconvolution analysis confirmed that corylin activated PI3K/Akt and MEK/ERK downstream signaling cascades. This study identifies corylin as a novel S1PR1 agonist with potential for drug design and presents a robust high-throughput screening method for S1PR1 agonist discovery.
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