Naunyn Schmiedebergs Arch. Pharmacol. [JOURNAL]
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200 papers
Cardio- and reno-protective effects of candesartan compared to lisinopril in a rat model of cardiorenal syndrome type 4: implication of oxidative stress and inflammation.
Eldesouky AMZ, Shehata MMA, Awwad IA … +1 more , Mohamed RMSM
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42262532 · Publisher ↗
Cardiorenal syndrome (CRS) is a progressive and life‑threatening disorder associated with high morbidity and mortality. This study aimed to compare the cardio‑ and reno‑protective effects of candesartan and lisinopril in...
Cardiorenal syndrome (CRS) is a progressive and life‑threatening disorder associated with high morbidity and mortality. This study aimed to compare the cardio‑ and reno‑protective effects of candesartan and lisinopril in a 5/6 nephrectomy model of type 4 CRS, with emphasis on their modulation of oxidative stress and inflammatory signaling pathways. Immediately after 5/6 subtotal nephrectomy, candesartan (10 mg/kg/day) or lisinopril (12.5 mg/kg/day) was administered by gastric gavage for 10 weeks. Serum urea and creatinine were measured 10 days post‑surgery. At the end of the treatment period, rats were euthanized, and blood, renal, and cardiac tissues were collected. Serum urea, creatinine, and cardiac BNP were quantified, along with renal and cardiac levels of SOD, MDA, NF‑κB, JAK‑2, STAT‑3, and TGF‑β. Histopathological examinations were also performed. Both candesartan and lisinopril significantly improved renal function, reduced arterial blood pressure, attenuated cardiac hypertrophy, lowered BNP levels, decreased renal and cardiac concentrations of MDA, NF‑κB, JAK‑2/STAT‑3, and TGF‑β, and increased SOD levels compared with the 5/6 nephrectomy group. Histopathological examination confirmed marked reductions in renal and cardiac tissue injury. Candesartan exerted greater reno‑protective effects than lisinopril in this model of CRS, whereas lisinopril offered slightly superior cardioprotective benefits. Both agents appear to mediate their therapeutic actions through attenuation of oxidative stress and inflammatory signaling.
Preliminary revelation of potential therapeutic targets related to ribosome biogenesis in lung adenocarcinoma based on bioinformatics analysis.
Yin N, Ren H
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42262531 · Publisher ↗
Ribosome biogenesis (RiboSis) serves as an important foundation for the malignant progression of tumors. In this study, bioinformatics was employed to evaluate the association between RiboSis and lung adenocarcinoma (LUA...
Ribosome biogenesis (RiboSis) serves as an important foundation for the malignant progression of tumors. In this study, bioinformatics was employed to evaluate the association between RiboSis and lung adenocarcinoma (LUAD) and to preliminarily uncover potential therapeutic targets. Analysis of DepMap CRISPR/RNAi data revealed that 73% of RiboSis genes are essential for cancer cell survival. RNA-seq analysis demonstrated that RiboSis remains continuously active in multiple types of tumors and is closely related to unfavorable clinical outcomes. Through Cox and LASSO-Cox regression analyses, DDX56, XRCC5, and FAM207A were identified as risk genes associated with LUAD. We further examined their co-mutation patterns with the top 10 most frequently mutated genes in LUAD. The results revealed a significant co-occurrence phenomenon among these three genes. Enrichment analysis linked these genes to the p53 pathway, cell cycle regulation, and immune cell infiltration. The CellMiner database revealed that these three genes are associated with resistance to multiple anticancer drugs. Subsequently, LUAD cell lines with knockdown of DDX56, XRCC5, and FAM207A, respectively, were constructed. The impacts of these three risk genes on the migration and invasion abilities of tumor cells were evaluated using CCK-8, Transwell, and cell scratch assays. The results showed that the knockdown of these genes could significantly inhibit tumor migration and invasion. In summary, this study preliminarily indicates that DDX56, XRCC5, and FAM207A may be potential therapeutic targets for LUAD, providing new strategies for the clinical treatment of LUAD.
Correction to: Chitosan‑embedded β‑cyclodextrin‑magnetic graphene oxide nanoparticles for curcumin loading: evaluating cytotoxicity and apoptosis induction in esophageal cancer.
Sajjadi SS, Einafshar E, Javid H … +3 more , Darban RA, Jafari N, Hashemy SI
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42259982 · Publisher ↗
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Identification of potential mechanisms of quercetin in diabetic peripheral neuropathy through integrated network pharmacology and experimental validation.
Chen Z, Li Z, Xue X … +6 more , Song W, Zhang R, Wang C, Yan B, Sun Q, Wu Q
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42259981 · Publisher ↗
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes characterized by oxidative stress and neuroinflammation. Quercetin, a natural flavonoid with antioxidant properties, has shown potential in treati...
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes characterized by oxidative stress and neuroinflammation. Quercetin, a natural flavonoid with antioxidant properties, has shown potential in treating various nerve injuries, but its mechanisms in DPN remain unclear. This research aims to explore the potential therapeutic mechanisms of quercetin in DPN through network pharmacology and experimental validation. In this study, streptozotocin (STZ)-induced diabetic rats were treated with quercetin for 12 weeks. Behavioral tests and histopathological examination were performed to evaluate nociceptive behaviors and sciatic nerve pathology, and biochemical and molecular assays were used to assess oxidative stress, inflammation, and myelin-related markers. Bioinformatics and network pharmacology were used to predict relevant targets and pathways, followed by in vivo validation in sciatic nerve tissues and in vitro verification using high glucose-exposed RSC96 Schwann cells. Quercetin improved pain thresholds and sciatic nerve morphology without significantly altering blood glucose or body weight. Moreover, quercetin restored the remyelination-related gene expression and attenuated oxidative stress and inflammatory responses in DPN rats. Bioinformatics and network pharmacology analyses indicated that the TXNIP/NLRP3 signaling played a key role. Subsequent in vivo and in vitro experiments further supported that quercetin reduced TXNIP expression and downregulated NLRP3 inflammasome-related gene expression. Our results indicate that quercetin attenuates DPN-like manifestations and mitigates oxidative stress and neuroinflammation. Its potential mechanism may be related to the regulation of TXNIP/NLRP3 inflammasome-related signaling, which lays a foundation for further research on DPN treatment.
Bile acids in Alzheimer's disease: a double-edged sword in gut-liver-brain signaling and neurodegeneration.
Basri R, Al-Kuraishy HM, Alruwaili M … +6 more , Al-Gareeb AI, Albuhadily AK, Alexiou A, Papadakis M, Faheem SA, Batiha GE
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42259980 · Publisher ↗
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau pathology, synaptic dysfunction, neuroinflammation, and metabolic impairment. Increasing evidence sugge...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposition, tau pathology, synaptic dysfunction, neuroinflammation, and metabolic impairment. Increasing evidence suggests that bile acids, traditionally recognized for their roles in lipid digestion and hepatic metabolism, act as endocrine signaling molecules that influence central nervous system (CNS) homeostasis. Through enterohepatic circulation and microbiota-dependent biotransformation, bile acid composition is dynamically regulated and can modulate peripheral metabolic and immune pathways with downstream effects on the brain. Notably, bile acid signaling via key receptors such as the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 and G-protein-coupled bile acid receptor 1 (TGR5/GPBAR1) has emerged as a mechanistic bridge linking liver-gut physiology to neuroinflammatory and neurodegenerative processes. Altered bile acid profiles have been reported in AD and mild cognitive impairment, with accumulating findings suggesting that hydrophobic secondary bile acids may contribute to blood-brain barrier (BBB) disruption and neurotoxicity. In contrast, hydrophilic bile acids may exert neuroprotective and anti-inflammatory effects. In addition, bile acids drive the release of gut hormones such as glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 19 (FGF19), highlighting indirect neurometabolic pathways relevant to cognition and neurodegeneration. This narrative review synthesizes current biochemical, experimental, and clinical evidence supporting a role for bile acid signaling in AD pathogenesis and progression. We discuss receptor-mediated pathways, microbiota-bile acid interactions, neuroimmune modulation, and translational perspectives, proposing that bile acid-based biomarkers and therapeutic strategies targeting FXR/TGR5 signaling may represent promising avenues for future AD intervention.
Exploring the medicinal potential of Bulbine latifolia (L.f.) Spreng.: a comprehensive review of phytochemicals and therapeutic applications.
Khalil AAK, Bae H
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42259979 · Publisher ↗
Bulbine latifolia (L.f.) Spreng. (syn. Bulbine natalensis), a succulent medicinal plant native to southern Africa and belonging to the family Asphodelaceae, has attracted considerable attention due to its ethnomedicinal...
Bulbine latifolia (L.f.) Spreng. (syn. Bulbine natalensis), a succulent medicinal plant native to southern Africa and belonging to the family Asphodelaceae, has attracted considerable attention due to its ethnomedicinal significance and pharmacological potential. Traditionally used for the treatment of wounds, skin disorders, infections, and metabolic conditions, this species is recognized for its diverse therapeutic applications in indigenous healthcare systems. Phytochemical investigations have revealed a wide range of bioactive constituents, including anthraquinones, triterpenes, sterols, fatty acids, and phenolic compounds. Recent studies have demonstrated its stimulant, antioxidant, anti-inflammatory, antimicrobial, antidiabetic, wound-healing, and apoptotic activities, supporting its relevance in both traditional and modern medicine. These bioactive compounds are known to modulate key biological pathways associated with oxidative stress, inflammation, and hormonal regulation. This review aims to provide a comprehensive and updated overview of B. latifolia, highlighting its phytochemical diversity, pharmacological properties, and underlying mechanisms of action, as well as its potential for future drug development.
Drug-associated cytokine release syndrome: a FAERS pharmacovigilance study with complementary transcriptomic analysis.
Zhang Y, Li X, Zhang J … +5 more , Chen S, Zang J, Wu D, Qin J, Ling W
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42257985 · Publisher ↗
Cytokine release syndrome (CRS) is a potentially severe systemic inflammatory toxicity associated with immunotherapies such as CAR-T cells, monoclonal antibodies, and immune checkpoint inhibitors. However, its real-world...
Cytokine release syndrome (CRS) is a potentially severe systemic inflammatory toxicity associated with immunotherapies such as CAR-T cells, monoclonal antibodies, and immune checkpoint inhibitors. However, its real-world reporting landscape across different drug classes remains incompletely characterized. We conducted a pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) from 2004 to 2024, focusing on reports coded as CRS. Disproportionality analyses were used to identify drugs associated with disproportionate CRS reporting, and temporal patterns were assessed using time-to-onset analyses and Weibull modeling. Logistic regression was used to explore factors associated with reported fatal outcomes among CRS cases. To provide complementary mechanistic context, exploratory transcriptomic and immune infiltration analyses were performed using the GEO dataset GSE255323. A total of 12,941 CRS reports were linked to 58 drugs, with CAR-T therapies and bispecific antibodies representing the most frequently reported triggers. Female-predominant reporting patterns were more commonly observed with conventional treatments, whereas male-predominant reporting patterns were more often observed with newer immunotherapies. CRS was typically reported within 3 days of drug administration, with a modest but statistically significant earlier onset in women. Factors associated with reported fatal outcomes included male sex, hematologic malignancies, and exposure to specific agents such as tisagenlecleucel. Complementary exploratory transcriptomic analyses suggested immune dysregulation involving myeloid and T-cell-related pathways, and immune deconvolution analyses indicated a pro-inflammatory effector-dominant profile in CRS samples. This study characterizes the real-world reporting landscape of drug-associated CRS and highlights sex-specific reporting patterns, early-onset clinical trajectories, and factors associated with reported fatal outcomes in FAERS. Complementary exploratory transcriptomic analyses suggest potential involvement of myeloid and T-cell dysregulation in CRS, providing additional context for future mechanistic and clinical studies.
Fabrication of vesicle-incorporated etoposide-loaded nanocochleates for improved anticancer efficacy.
Nagoba SN, Fugate AR, Singh AK … +4 more , Dodiya R, Mali SS, Singh S, Patil PB
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42257984 · Publisher ↗
Cancer is a major global health concern, characterized by uncontrolled cell proliferation and high mortality rates. Conventional chemotherapeutic agents often suffer from poor selectivity and systemic toxicity, limiting...
Cancer is a major global health concern, characterized by uncontrolled cell proliferation and high mortality rates. Conventional chemotherapeutic agents often suffer from poor selectivity and systemic toxicity, limiting their clinical utility. Etoposide, a potent topoisomerase II inhibitor, is widely used to treat various types of cancers such as lung, testicular, and lymphomas. However, its clinical application is hampered due to low bioavailability and rapid clearance. To address, these limitations, nanocarrier-based systems such as liposomes and nanocochleates have been fabricated and explored. In the present study, etoposide was encapsulated within liposomes using the ethanol injection method. The optimized liposomal batch (ETNL5) exhibited favorable physicochemical properties such as entrapment efficiency (75.80 ± 1.26%), particle size (210.7 ± 0.15 nm), zeta potential (- 27.6 mV), and in vitro drug release of 92.34%. This formulation was further converted into nanocochleates (ETNC) using calcium-induced fusion with DMPG-Na and cholesterol. Pharmacokinetic evaluation demonstrated that ETNC significantly improved systemic exposure in regulated release format. ETNC showed the highest C (0.50 ± 1.52 µg/mL) and AUC (116.74 ± 9.16 µg·min/mL), along with extended half-life (150.88 ± 13.25 min) and MRT (240.14 ± 36.98 min), indicating prolonged circulation and reduced clearance (0.08 mg/(µg/mL)/min), while the tissue distribution studies revealed enhanced lung accumulation (28.99 ± 0.02 µg/g) with minimal off-target exposure, suggesting potential for site-specific delivery. Overall, ETNC provide a stable, efficient, and targeted drug delivery platform with promising potential for improving cancer therapy. Their ability to enhance bioavailability, reduce toxicity, and selectively target organs makes them a superior alternative to conventional formulations.
A real-world disproportionality analysis of dupilumab safety in children aged 0-5 years with atopic dermatitis.
Yan L, Cen H, Yi B … +1 more , Fang Y
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42257983 · Publisher ↗
Dupilumab is approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children as young as 6 months, but real-world safety reporting in children aged 0-5 years remains limited. We conducted a retrospect...
Dupilumab is approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children as young as 6 months, but real-world safety reporting in children aged 0-5 years remains limited. We conducted a retrospective pharmacovigilance study using the US FDA Adverse Event Reporting System (FAERS) from Q1 2022 to Q3 2025 to characterize dupilumab-associated adverse events (AEs) in children aged 0-5 years with AD in which dupilumab was the primary suspect drug. Disproportionality analysis at the System Organ Class (SOC) and Preferred Term (PT) levels were performed using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and empirical Bayesian geometric mean (EBGM), following READUS-PV. Time-to-onset (TTO) was described when valid dates were available. A total of 2,798 reports were identified (median age 3 years; 57.6% male), of which 187 (6.7%) were serious. At SOC level, skin and subcutaneous tissue disorders (n = 2,609; ROR 12.92) and eye disorders (n = 463; ROR 5.63) met predefined signal criteria across all four algorithms. At PT level, high-frequency events included pruritus, dry skin, rash and eczema and medication-use issues such as incorrect dose and inappropriate schedule. High-disproportionality PTs included eyelid exfoliation, eyelid skin dryness, dry eye, ocular hyperaemia and skin-barrier-related PTs such as skin fissures and skin exfoliation. For TTO, most skin and ocular PTs occurred < 30d after initiation. In children aged 0-5 years with AD, FAERS reports suggest early-onset cutaneous and ocular adverse events after dupilumab. No SOC-level disproportionality signal was detected for infections and infestations or neoplasms, but rare risks cannot be excluded. Selected PTs nevertheless showed disproportionate reporting, supporting proactive ocular monitoring, caregiver education, and continued surveillance.
Comprehensive evaluation of Lactobacillus strains and Bacillus coagulans against Bisphenol-A induced neuronal and cardiac toxicities.
Dongre S, Patel A, Patel M … +6 more , Kaushik G, Shah U, Patel S, Raval K, Koria H, Patel A
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42257982 · Publisher ↗
Bisphenol A (BPA) has emerged as an environmental pollutant in the last decade. It is imperative to reduce and limit the absorption of this chemical as it can negatively affect vital organs, including brain and heart. Th...
Bisphenol A (BPA) has emerged as an environmental pollutant in the last decade. It is imperative to reduce and limit the absorption of this chemical as it can negatively affect vital organs, including brain and heart. There is no direct curative option for BPA-induced toxicity hence, to bridge this gap, this study was conducted to evaluate the prophylactic effects of Bacillus coagulans against BPA-induced neuro- and cardio- toxicities. In silico techniques were utilized to study the toxicophore of BPA, followed by in vitro probiotic studies to select the best strain with the most physiological stability and pharmacokinetic properties. Positive effect of probiotic against cytotoxicity produced by BPA was studied on PC12 and H9c2 cell lines. After model standardization to select suitable dose for BPA induced toxicities, 42 male wistar rats were divided into seven groups for in vivo studies: normal control (Group 1), probiotic (Group 2), BPA alone (Group 3), BPA + standard treated (Group 4), BPA + probiotic (low dose) (Group 5), BPA + probiotic (medium dose) (Group 6), and BPA + probiotic (high dose) (Group 7). Morphological parameters, blood pressure, electrocardiogram, inflammatory cytokine level, antioxidant levels, brain and heart biomarkers, and histology were evaluated to investigate the protective effects. The probiotic showed protective effects, reflected by modulation of MDA, BDNF, CK-MB and IL-6 levels, along with improved tissue histology; however, a consistent dose-dependent response was not observed across all evaluated parameters. Thus, the findings suggest that Bacillus coagulans may have prophylactic potential against BPA-induced neuronal and cardiac toxicities.
Protective effects of dexpanthenol against diatrizoate-induced contrast nephropathy via the SIRT1-p53-Bcl-2/Bax pathway in rats.
Havabulut CM, Gündüz D, Sarman E … +5 more , İlhan İ, Tepebaşı MY, Gülal A, Savran M, Aşcı H
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42257981 · Publisher ↗
Contrast agents are widely used in medical imaging to improve tissue differentiation, but they can cause serious inflammatory responses, including contrast-induced nephropathy (CIN). Dexpanthenol (DEX) is known for its a...
Contrast agents are widely used in medical imaging to improve tissue differentiation, but they can cause serious inflammatory responses, including contrast-induced nephropathy (CIN). Dexpanthenol (DEX) is known for its antioxidant, anti-inflammatory, and anti-apoptotic properties. This study aimed to investigate the potential protective effects of dexpanthenol in a rat model of diatrizoate-induced CIN. In this study, 32 Wistar albino rats were randomly divided into four groups: control, Urografin (URO; 10 mL/kg, intraperitoneal [i.p.]), URO + DEX (500 mg/kg, i.p. for 3 days), and DEX alone. Renal function markers (serum urea and creatinine), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured. Histopathological evaluation and immunohistochemical analysis of tumor necrosis factor-alpha (TNF-α) and caspase-3 (Cas-3) were performed. Additionally, SIRT1, Bcl-2, Bax, and p53 mRNA expression levels were assessed. URO administration increased TOS and OSI values and caused significant renal histopathological damage. TNF-α and Cas-3 immunoreactivity, along with Bax and p53 gene expression, were significantly elevated, while Bcl-2 and SIRT1 expression was suppressed. DEX treatment provided partial improvement in these changes, contributed to the preservation of renal architecture, and was associated with improvements in biochemical and molecular parameters approaching those of the control levels. In conclusion, DEX may exert nephroprotective effects against CIN by reducing oxidative stress, inhibiting pro-inflammatory and apoptotic pathways, and increasing anti-apoptotic gene expression. These findings provide a preclinical basis supporting the idea that dexpanthenol is a promising candidate for further translational and clinical studies in contrast-induced renal injury.
Quarterly persistence as a signal prioritization framework in FAERS: an analysis of the 2025 public-use releases.
Martínez-Cadena JA, Garza-Villafuerte V
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42257980 · Publisher ↗
To develop and apply a quarterly pharmacovigilance workflow for the 2025 FDA Adverse Event Reporting System (FAERS) public-use XML releases, with emphasis on temporal persistence, cohort sensitivity, and prioritization-o...
To develop and apply a quarterly pharmacovigilance workflow for the 2025 FDA Adverse Event Reporting System (FAERS) public-use XML releases, with emphasis on temporal persistence, cohort sensitivity, and prioritization-oriented signal characterization. The raw input consisted of 12 quarterly FAERS XML files (approximately 8.58 GB), which were parsed into report-level drug-reaction pairs using a chunked workflow. The main analysis used a PS-clinical cohort including primary suspect drugs from serious reports, whereas a sensitivity analysis expanded this definition to a PS + SS-clinical cohort by including secondary suspect drugs. Quarterly product-reaction pairs were screened using a disproportionality rule requiring , proportional reporting ratio , , and a lower 95% confidence bound of the reporting odds ratio greater than 1. A more conservative subset was defined by , followed by post-screening refinement for temporal comparison. Under the PS-clinical cohort, the quarterly retained sets ranged from 41,897 to 47,220 pairs, and the annual union contained 82,565 unique retained pairs. Of these, 18,629 (22.56%) were detected in all four quarters. Pairwise Jaccard similarities ranged from 0.4027 to 0.4845, indicating moderate but structured temporal continuity, with the strongest overlap between Q3 and Q4. Fully persistent 4/4 pairs showed higher support counts and larger mean values than quarter-specific 1/4 pairs, whereas mean PRR did not differ materially between these groups. Within the 4/4 core, most pairs were relatively stable over time, while only a small subset showed marked temporal imbalance. Expansion to the PS + SS-clinical cohort substantially increased both the retained signal space and the 4/4 core, while leaving the overall temporal overlap pattern broadly similar. Quarterly persistence may provide an additional and interpretable dimension for internal FAERS-based signal characterization and prioritization. Rather than replacing disproportionality metrics, it may complement them by highlighting reproducibility, continuity, and temporal structure across quarterly retained signal sets. External validation against independent pharmacovigilance reference standards remains an important direction for future work.
Correction to: Critical analysis of withdrawn drug applications in marketing authorization procedures of the European Medicines Agency (EMA) 2006-2024.
Hitsch F, Seifert R
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42252342 · Publisher ↗
Abstract loading — click title to view on PubMed.
Temozolomide and ruxolitinib combination modulates miRNA-associated regulatory networks in glioblastoma stem cells.
Ozates NP, Asik A, Bagca BG … +1 more , Avci CB
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42252341 · Publisher ↗
Glioblastoma is an aggressive primary brain tumor characterized by high recurrence rates and resistance to standard therapies, including temozolomide (TMZ). Emerging evidence suggests that microRNAs (miRNAs) play a criti...
Glioblastoma is an aggressive primary brain tumor characterized by high recurrence rates and resistance to standard therapies, including temozolomide (TMZ). Emerging evidence suggests that microRNAs (miRNAs) play a critical role in regulating treatment response and tumor progression. In this study, we investigated the effects of TMZ and the JAK inhibitor ruxolitinib, alone and in combination, on miRNA expression profiles in glioblastoma cancer stem cells. miRNA expression levels were analyzed using quantitative real-time PCR, and differential expression was evaluated using the 2 method. TMZ treatment increased the expression of oncogenic miRNAs, including hsa-miR-19a-3p, hsa-miR-221-3p, and hsa-miR-10a-5p, whereas ruxolitinib treatment reduced their expression levels. Combination treatment attenuated the TMZ-induced upregulation of these miRNAs. Bioinformatics analyses were performed to identify target genes and associated signaling pathways. Predicted targets were obtained using TargetScan and further supported by experimentally validated interactions from miRTarBase. KEGG pathway enrichment analysis revealed significant associations with cancer-related pathways, including PI3K-Akt, MAPK, Wnt, and Hippo signaling pathways. Network analysis highlighted key genes such as BCL2L11, PTEN, and SOCS family members. Overall, our findings suggest that TMZ may induce oncogenic miRNA expression as part of an adaptive response, while ruxolitinib may counteract this effect. Targeting miRNA-mediated regulatory networks in combination with pathway inhibition may represent a promising strategy to overcome therapeutic resistance in glioblastoma.
Phthalocyanine-based mouth gel as an adjunct to non-surgical periodontal treatment: a randomized controlled trial.
Neto SOP, Rosalen PL, da Cruz Pegoraro JV … +10 more , Andrade ISSE, Reis ALM, Costa IS, Silva GT, de Oliveira GJPL, Vilhena FV, Ikegaki M, Pigossi SC, Fernandes LA, Franchin M
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42249969 · Publisher ↗
This study aimed to evaluate the effect of topical application of a mouth gel formulation containing iron tetracarboxyphthalocyanine (FeTcPc) during non-surgical periodontal treatment. Forty-seven individuals with period...
This study aimed to evaluate the effect of topical application of a mouth gel formulation containing iron tetracarboxyphthalocyanine (FeTcPc) during non-surgical periodontal treatment. Forty-seven individuals with periodontitis underwent a standard periodontal treatment (scaling and root planing), followed by adjuvant therapy according to the = groups: Vehicle Group (n = 15), receiving local application of the FeTcPc gel vehicle; Chlorhexidine (CLX) Group (n = 16), receiving local application of 0.12% chlorhexidine gel; and FeTcPc Group (n = 16), receiving local application of 1% FeTcPc-containing gel. Clinical evaluations were performed at baseline and after 45 days. No statistically significant differences were observed between the study groups in any periodontal clinical parameters at baseline or 45 days after treatment. In the intragroup analysis, the mean probing depth (PD) and the percentage of sites with PD ≤ 3 mm and PD = 4-5 mm showed a statistically significant reduction at 45 days in both the vehicle and FeTcPc groups (p < 0.05). The percentage of sites with bleeding on probing and the plaque index demonstrated a statistically significant reduction after 45 days in all groups (p < 0.05). The use of FeTcPc mouth gel as an adjunct to non-surgical periodontal therapy did not improve the clinical periodontal parameters compared to CLX or the vehicle group in this study.
Dietary phytoestrogen ameliorates ovarian toxicant-induced neurotoxicity: mechanistic and metabolic insights.
Shandilya A, Hajare S, Arwind DA … +4 more , Giri CK, Gajbhiye R, Ravichandiran V, Parihar VK
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42249968 · Publisher ↗
Premature ovarian insufficiency (POI) poses serious neurological risks such as mood disturbances, cognitive decline, early brain structural changes, neural degeneration, and a heightened risk of dementia and AD in women....
Premature ovarian insufficiency (POI) poses serious neurological risks such as mood disturbances, cognitive decline, early brain structural changes, neural degeneration, and a heightened risk of dementia and AD in women. This study aims to investigate cognitive performance, mitochondrial malfunction, and persistent neuroinflammation in a mouse model of premature ovarian failure induced by ovatoxin vinylcyclohexene diepoxide (VCD), as well as the potential use of dietary phytoestrogen therapy to combat the accelerated brain ageing-like phenotype and chronic inflammation associated with ovarian insufficiency. The data from our neurobehavioural evaluations showed impaired object recognition memory, along with enhanced anxiety and depression in the VCD-intoxicated mice. This was accompanied by a water maze assessment, which indicates that long-term estrogen depletion negatively affected spatial learning and memory retrieval. This is demonstrated by the increased time required for VCD mice to locate the hidden platform and their inability to find the virtual platform during the memory retrieval assessment. In VCD-challenged mice, there were clear signs of compromised learning and memory across the behavioural tests, along with impaired mitochondrial complexes and increased β-amyloid protein expression. Furthermore, in conjunction with reduced estrogen levels, VCD mice showed enhanced neuronal inflammation, as evidenced by heightened expression of neuroinflammatory mediators, including HMGB1, TLR-4, NF-kappa B, CD68 and TREM2. Furthermore, our study has shown that a phytoestrogen diet can restore compromised mood and memory functions. The improvements in learning, memory, and cognitive abilities associated with this dietary intervention were evidenced by reduced neuroinflammation, restored mitochondrial respiratory complexes, enhanced neurotrophic factor levels, and decreased β-amyloid protein expression. Consequently, the current results provide preliminary support for the hypothesis that a diet rich in phytoestrogens could be a viable strategy to mitigate accelerated brain ageing and address mood and memory challenges associated with ovarian insufficiency.
Therapeutic potential of harmine in polycystic ovarian syndrome: regulation of TNF-α/IL-6-mediated inflammation, Nrf2/keap-1 signaling, and ovarian steroidogenesis in Sprague-Dawley rats.
Ahmad A, Saleem A
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42249967 · Publisher ↗
Polycystic ovarian syndrome (PCOS) is an intricate endocrine and metabolic disorder affecting reproductive-age women. This research focused on assessing the therapeutic potential of harmine in letrozole-induced PCOS rat...
Polycystic ovarian syndrome (PCOS) is an intricate endocrine and metabolic disorder affecting reproductive-age women. This research focused on assessing the therapeutic potential of harmine in letrozole-induced PCOS rat model. PCOS was induced in all the groups except normal control by oral administration of letrozole (1 mg/kg) for consecutive 28 days. After confirmation of PCOS, normal and disease controls were treated with vehicle, clomiphene citrate (5.25 mg/kg) was administered as a standard drug, and harmine as treatment compound at 2.5, 5.0, and 10 mg/kg orally for 28 days daily. Letrozole administration in diseased rats displayed disrupted estrous cycle irregularity, insulin resistance, cystic ovarian morphology, and hyperandrogenism along with upregulation of metabolic and lipid profile and alteration in hormonal and hematological parameters. Treatment with harmine (2.5-10 mg/kg) was remarkably (p < 0.05) normalize the metabolic and lipid profile, restored the hormonal imbalance, and improved ovarian histology. Treatment with harmine (2.5-10 mg/kg) notably reduced the serum level TNF-α, and IL-6 in contrast to disease control. Harmine-treated rats exhibited the down regulation of mRNA expression of TNF-α, IL-6, PGR, and Keap-1 while upregulated FSHR, CYP19A1, and Nfr-2 as equated to disease control. However, harmine demonstrated dose-dependent improvement in mRNA expression that linked with ovarian function. These findings concluded that harmine exhibited promising therapeutic potential for PCOS by modulating metabolic, endocrine, anti-oxidant, anti-inflammatory, and steroidogenic markers. Besides, harmine was safe in acute usage and LD50 > 2000 mg/kg.
Network pharmacology identifies repurposable drugs targeting host pathways across the oral-gut-lung axis.
Thamanna L, Chellapandi P
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42249966 · Publisher ↗
The systematic integration of heterogeneous host-pathogen interaction data with disease modules and pharmacological knowledge remains a major challenge in translational biomedical informatics. Network medicine offers a p...
The systematic integration of heterogeneous host-pathogen interaction data with disease modules and pharmacological knowledge remains a major challenge in translational biomedical informatics. Network medicine offers a promising strategy for identifying conserved regulatory vulnerabilities and therapeutic repositioning opportunities across distinct mucosal ecosystems. We developed a scalable multilayer network integration framework that unifies pathogen-host protein interactions, disease-risk gene modules, and drug-target associations into a consolidated human interactome. The integrated network comprised 7,262 human proteins, 17,016 high-confidence protein-protein interactions, nine bacterial pathogens, four respiratory viruses, and 514 FDA-approved drugs. Network topology was quantitatively characterized using complementary centrality metrics (degree, betweenness, closeness, clustering coefficient, and topological coefficient) to identify high-influence host regulators. Drug prioritization employed a multi-criteria ranking pipeline integrating functional network scoring (CoDReS), structural similarity clustering (Tanimoto-based hierarchical modeling), and pharmacokinetic constraint filtering (ADMET profiling). Pathway enrichment analysis was performed to identify convergent biological mechanisms. The integrative framework identified conserved cross-ecosystem regulatory hubs, including PPARG, CDC42, JUN, RHOA, and CAV1, which link microbial perturbations to cardiometabolic and inflammatory disease pathways. Centrality-weighted drug prioritization consistently ranked indomethacin, ibuprofen, dexibuprofen, mesalazine, and cannabidiol as high-confidence repositioning candidates for densely connected host networks. Enrichment analyses demonstrated convergence on immune signaling pathways, cytoskeletal remodeling, PPAR signaling, and focal adhesion networks. This study presents a reproducible and generalizable network medicine workflow that formalizes interactome construction, multi-metric centrality assessment, and composite drug ranking in a unified analytical framework. The proposed strategy enables the systematic identification of conserved host regulatory vulnerabilities and repositionable therapeutics across infectious and chronic inflammatory diseases, thereby advancing host-directed therapeutic discovery in translational biomedical informatics.
Immunopharmacologsical and structural insights into Rift Valley fever virus envelope glycoproteins: an immunoinformatics approach to multi-epitope vaccine design.
Aziz T, Alshehri MA, Aljumaa MA … +2 more , Sagini HA, Nabi G
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42249965 · Publisher ↗
Rift Valley fever (RVF) is a clinically zoonotic pathogen associated with severe systemic and neurological complications, for which no approved vaccine is currently available. This study aimed to design a novel chimeric...
Rift Valley fever (RVF) is a clinically zoonotic pathogen associated with severe systemic and neurological complications, for which no approved vaccine is currently available. This study aimed to design a novel chimeric multi-epitope vaccine candidate targeting the RVFV Envelope polyprotein (Gn and Gc) via an integrative immunoinformatic and structural modeling approach, targeting viral envelope glycoproteins which play a crucial role in host cell entry and immune recognition. The epitopes used in the vaccine assembly were selected on the basis of antigenicity, allergenicity, and toxicity, then linked to the RS09 adjuvant and optimized using linkers. The vaccine's 3D model was built using AlphaFold 3, and its potential to bind to the human TLR4 receptor (PDB ID: 4G8A) was investigated using ClusPro 2.0 docking. Population coverage and immune simulation were conducted using IEDB and the C-ImmSim server, respectively. The vaccine is highly antigenic, soluble, stable, and has a global population coverage of more than 90%. In addition, the vaccine was found to be effective as indicated by a high binding energy and good complementarity to the complex formed by the TLR4 receptor. This study demonstrates that a highly effective and safe vaccine candidate for global RVF prevention is feasible and should be considered for development.
Drug supply shortages and their consequences for the medical profession: a survey in Germany and Austria.
Rotter JM, Seifert R
Naunyn Schmiedebergs Arch Pharmacol · 2026 Jun · PMID 42249097 · Publisher ↗
Drug supply shortages are increasingly becoming a critical topic in the treatment of patients. Not only the reasons for the supply shortages are important but also their consequences for the medical profession. Firstly,...
Drug supply shortages are increasingly becoming a critical topic in the treatment of patients. Not only the reasons for the supply shortages are important but also their consequences for the medical profession. Firstly, this paper identifies which drug shortages have particularly affected medical doctors. Secondly, the additional time required for medical doctors due to supply shortages is analysed. A survey was conducted with 895 physicians from Germany and Austria using a purposive sampling method. The survey targets the supply shortages and its consequences for the medical profession of 20 commonly used drugs. All survey questions referred to the time span from November 2022 to January 2024. Penicillin V and amoxicillin emerged as the drugs most seriously affected by drug supply shortage although the severity to which physicians were affected by the individual 20 drug shortages varied regionally (Germany/Austria), depending on the place of work (practice/clinic) and the physicians' specialty. Drug shortages reported by survey participants did not necessarily match official reporting of drug shortage. There was also a substantial increase in time required for medical doctors handling drug shortages. The most additional time burden per affected drug was recognised in haematology/oncology with 46 min, followed by psychiatry (37 min), nephrology (37 min), and general medicine (28 min). The identification of specific critical drugs, specific disciplines, and defined time-consuming factors offer starting points for improvements. Moreover, exact reporting of drug shortages by official authorities is important. Encouraging more judicious prescribing practices may help reduce perceived shortages.
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