Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Unraveling potent therapeutic potentials of tanshinones, lipophilic abietane diterpenes: a holistic literature review.","authors":"Shymaa I A Abdel-Dayem, Rania M Kamal, Heba R Ghaiad, Mariam K Ahmed, Aya H Eid, Ahmed M El-Dessouki, Ola Elazazy, Fatma Saeed El-Tokhy, Sally A Fahim, Riham A El-Shiekh, Eman M Abd Elghany","doi":"10.1007/s00210-026-05664-4","DOIUrl":"10.1007/s00210-026-05664-4","url":null,"abstract":"<p><p>Tanshinones, a class of lipophilic abietane-type diterpenoid, represents the major bioactive constituents of Salvia miltiorrhiza Bunge (Danshen), a key herb in traditional Chinese medicine with growing therapeutic importance. This review offers an in-depth overview of tanshinones from phytochemical and pharmacological perspectives. The review outlines the biosynthetic pathway, highlights the key synthetic approaches, and provides a detailed chemical and stereochemical characterization of the major tanshinones isomers. Pharmacologically, tanshinones exhibit broad, multi-system activities including antioxidant and anti-inflammatory effects, cardiovascular and hepatorenal protection, antitumor activity, immunomodulatory effects, and therapeutic benefits across neurological, metabolic, skeletal, respiratory, and infectious diseases. Despite their broad therapeutic potential, progression of tanshinones toward clinical application is restricted by low oral bioavailability, poor aqueous solubility, and rapid metabolism. To overcome these barriers, novel drug-delivery strategies including lipid nanocapsules, liposomes, polymeric nanoparticles, solid liquid nanoparticles, microemulsions, and nanoemulsions significantly improve solubility, stability, and pharmacokinetics. This review integrates the current evidence to guide future optimization and mechanistic exploration and support the development of innovative nanoformulations for next-generation tanshinone-based therapies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20215-20260"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13695630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"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":"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13695664/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alamandine attenuates stress-induced inflammation, oxidative stress, and intestinal histopathological alterations in a chronic unpredictable mild stress model of depression.","authors":"Aysu Kilic, Betul Esra Ipek, Yasin Ali Cimen, Mert Yilmaz, Fatma Bedia Karakaya Cimen, Emine Rumeysa Hekimoglu, Huri Demirci, Savas Ustunova","doi":"10.1007/s00210-026-05612-2","DOIUrl":"10.1007/s00210-026-05612-2","url":null,"abstract":"<p><p>Depression is increasingly recognized as a systemic disorder associated with chronic inflammation, oxidative stress, and disturbances in the gut-brain axis. This study aimed to investigate whether alamandine modulates chronic stress-induced alterations in the intestine and liver by assessing histopathological changes, inflammatory responses, and oxidative stress parameters in a chronic unpredictable mild stress (CUMS) model. Male rats were exposed to CUMS for 35 days, and the effects of Alamandine and the Mas receptor antagonist A779 were evaluated. Serum inflammatory cytokines (TNF-α, IL-6), liver cytokines (IL-6, IL-1β), oxidative stress markers including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA), as well as biochemical parameters (AST, ALT, total protein) were analyzed. Histopathological examination of intestinal and colonic tissues was also performed. CUMS significantly increased serum cortisol and pro-inflammatory cytokines, indicating systemic inflammation, while elevated IL-6 and IL-1β levels in liver tissue suggested a localized inflammatory response. Oxidative stress findings showed impaired antioxidant defense and increased lipid peroxidation. Despite these changes, AST, ALT, and total protein levels remained unchanged, indicating no overt hepatic injury. Histologically, CUMS caused intestinal villus degeneration, inflammatory infiltration, and reduced goblet cell numbers, whereas the colon exhibited milder epithelial alterations. Alamandine treatment attenuated inflammatory and oxidative responses and improved intestinal mucosal integrity, with partial restoration of goblet cells. These findings suggest that alamandine attenuates chronic stress-induced inflammatory, oxidative, and histopathological alterations in intestinal and hepatic tissues. The results further support a potential protective role of the RAS pathway in peripheral tissue injury associated with chronic stress.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20403-20415"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13695625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin analogues suppress cellular pro-inflammatory mediators and reduce edema.","authors":"Kifayat Ullah, Wenyun Zhu, Syed Wadood Ali Shah, Haya Hussain, Abid Ullah, Farman Ali Khan, Nasir Mehmood Khan, Naveed Ullah Khan, Shujaat Ahmad, Guoqiang Xu","doi":"10.1007/s00210-026-05629-7","DOIUrl":"10.1007/s00210-026-05629-7","url":null,"abstract":"<p><p>Inflammation is a normal physiological response to adverse stimuli mediated by numerous pro-inflammatory cytokines and signaling pathways. Although curcumin modulates key inflammatory pathways, the role of its analogues in inflammation is not fully elucidated. This study explores the anti-inflammatory potential of curcumin analogues (K1-K4) in vitro and in vivo models. Four curcumin analogues (K1-K4) were successfully synthesized and assessed for their anti-inflammatory efficacy at doses of 10 and 20 mg/kg body weight. All the curcumin analogues, particularly K1 and K4 demonstrated significant attenuation of absolute post-injection carrageenan-induced paw edema in mice, exhibiting a significant response at both doses. The maximum inhibition of paw edema was achieved after 2 h, i.e., 62.45% for K1 and 62.09% for K4 at a dose of 20 mg/kg compared to diclofenac (66.10%). The analogues markedly ameliorated ear edema and prominently alleviated the absolute post-injection paw edema mediated by histamine in mice. Among the analogues, K1 and K4 exhibited the highest activity and markedly attenuated the edema in all models. Mechanistically, the curcumin analogues except K2 significantly downregulated iNOS, COX2, and p-p65 protein levels in RAW264.7 cells. The mRNA expression of inflammatory cytokines was also notably diminished in RAW264.7 cells. Moreover, K1 was observed to affect markers associated with apoptosis among the curcumin analogues. The findings demonstrate that curcumin analogues suppress key pro-inflammatory mediators in cells and reduce edema in vivo, highlighting their preliminary anti-inflammatory activity in acute inflammation models.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20345-20358"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369305","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":"Role of CXCL16/ADAM10 signaling in methotrexate-induced nephrotoxicity and its modulation by simvastatin.","authors":"Alulu Alradhi, Abdulrahman A Alelowi, Ahmad H Alhowail, Maha A Aldubayan, Mohamed S Abdel-Bakky","doi":"10.1007/s00210-026-05658-2","DOIUrl":"10.1007/s00210-026-05658-2","url":null,"abstract":"<p><p>Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent; however, one of clinical limitations of its use is renal toxicity. CXCL16 is a transmembrane chemokine that can be cleaved by ADAM family proteases, particularly ADAM10, to generate a soluble form that acts as a chemoattractant for CXCR6-expressing cells such as T lymphocytes. This process may contribute to inflammatory renal injury. This study investigated the role of CXCL16/ADAM10 in MTX-induced nephrotoxicity and assessed the renoprotective effects of simvastatin (SIM). Fifty male Wistar rats were randomly assigned to five groups: control, SIM (40 mg/kg), MTX (20 mg/kg) and two combination groups receiving MTX with SIM (10 or 40 mg /kg). SIM was administered orally for 10 days, while MTX was administered as a single i.p. dose on day 4. Hematological parameters, markers of renal function, and renal histopathology were assessed. In addition, the expression of CXCL16, ADAM10, CD3, and fibrinogen was evaluated. MTX administration significantly elevated renal function markers compared with the control and SIM groups. Histopathological analysis revealed glomerular atrophy and mononuclear inflammatory cell infiltration in MTX-treated rats. Moreover, MTX markedly increased the expression of CXCL16, ADAM10, CD3, and fibrinogen in the glomeruli and tubulointerstitial regions. Treatment with SIM significantly improved renal function markers, attenuated histopathological damage, and reduced the expression of these inflammatory and injury-related proteins. CXCL16 and its processing enzyme ADAM10 play important roles in MTX-induced renal toxicity. SIM demonstrated a dose-dependent protective effect against MTX-induced renal injury, likely through modulation of inflammatory pathways involving CXCL16/ADAM10 signaling.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":"20359-20373"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369290","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}