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Retraction Note: Protective effects of hesperidin against MTX-induced hepatotoxicity in male albino rats. 注:橙皮苷对甲氧蝶呤诱导的雄性白化大鼠肝毒性的保护作用。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-20 DOI: 10.1007/s00210-026-06017-x
Ramadan M Abdelaziz, Ahmed Z Abdelazem, Khalid S Hashem, Yasser A Attia
{"title":"Retraction Note: Protective effects of hesperidin against MTX-induced hepatotoxicity in male albino rats.","authors":"Ramadan M Abdelaziz, Ahmed Z Abdelazem, Khalid S Hashem, Yasser A Attia","doi":"10.1007/s00210-026-06017-x","DOIUrl":"https://doi.org/10.1007/s00210-026-06017-x","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224525","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}
引用次数: 0
Melatonin nanoemulgel for dermal applications: from formulation to in vivo imaging validation. 褪黑素纳米凝胶用于皮肤应用:从配方到体内成像验证。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-19 DOI: 10.1007/s00210-026-05994-3
Juhi Mishra, Dhruv Kumar Nishad, Neelam Poonia, Viney Lather, Deepti Pandita
{"title":"Melatonin nanoemulgel for dermal applications: from formulation to in vivo imaging validation.","authors":"Juhi Mishra, Dhruv Kumar Nishad, Neelam Poonia, Viney Lather, Deepti Pandita","doi":"10.1007/s00210-026-05994-3","DOIUrl":"https://doi.org/10.1007/s00210-026-05994-3","url":null,"abstract":"<p><p>Radiation-induced dermatitis is a prevalent side effect of radiotherapy worldwide. Conventional treatment strategies often fall short of achieving optimal therapeutic efficacy, primarily due to inadequate retention on the skin surface. This limitation has motivated research to find new nanotechnology-based treatment approaches to enhance therapeutic outcomes. Nanoformulations have emerged as a promising solution, offering improved therapeutic outcomes. In this study, authors investigated a combination therapy consisting of melatonin (MLT), vitamin E (VE), and N-acetyl cysteine (NAC). MLT is a naturally occurring hormone that has anti-inflammatory and antioxidant properties that may help treat cancer. It plays a crucial part in protecting healthy tissues by neutralizing various free radical scavengers generated by IR pro-oxidant enzymes that are triggered after exposure to IR. VE and NAC also depict radiomitigator properties. In the present study, nanoemulgel was formulated with Carbopol®940, which acts as a gelatinizing agent to facilitate effective delivery of these therapeutic agents at the target site. Pseudoternary phase diagrams were prepared to classify the area of nanoemulsion region. Globule size and zeta potential of optimized nanoemulsion formulation were observed to be 113.84 ± 0.648 nm and 34.2 ± 0.907 mV, respectively. Further, in vitro skin release studies showed 49.94 ± 3.01% cumulative release of MLT from nanoemulgel a time frame of 24 h. And the formulation followed Korsmeyer-Peppas model, which indicates that drug release is non-fickian. An FTIR analysis confirmed that MLT's characteristic peaks were preserved in the formulations, demonstrating that no interaction occurred between the constituents. The DSC thermogram of MLT nanoemulgel showed no sharp melting peak, suggesting molecular dispersion in oil phase. Additionally, gamma scintigraphy evaluation confirmed the formulation's long-term skin retention. In experimental results, nanoemulsion gel showed enhanced permeability and retention, making it a promising transporter for topical deliveries of bioactives for radiation-induced dermatitis prevention.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220451","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}
引用次数: 0
Evaluation of antiseptic drug candidate pyridosept in preclinical in vivo toxicity studies. 抗菌候选药物吡哆醇在临床前体内毒性研究中的评价。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-19 DOI: 10.1007/s00210-026-05997-0
Renata Kazakova, Alfiya Fakhrieva, Mariya Agafonova, Elena Bulatova, Olga Kirichenko, Albina Malanyeva, Milana Mansurova, Ilnur Ganiev, Natalia Komcharova, Ivan Raginov, Sergey Sapozhnikov, Nikita Shtyrlin, Yurii Shtyrlin
{"title":"Evaluation of antiseptic drug candidate pyridosept in preclinical in vivo toxicity studies.","authors":"Renata Kazakova, Alfiya Fakhrieva, Mariya Agafonova, Elena Bulatova, Olga Kirichenko, Albina Malanyeva, Milana Mansurova, Ilnur Ganiev, Natalia Komcharova, Ivan Raginov, Sergey Sapozhnikov, Nikita Shtyrlin, Yurii Shtyrlin","doi":"10.1007/s00210-026-05997-0","DOIUrl":"https://doi.org/10.1007/s00210-026-05997-0","url":null,"abstract":"<p><p>The purpose of this study is to assess the safety profile of the antiseptic drug candidate pyridosept in preclinical in vivo toxicity tests. The safety of pyridosept was assessed in acute toxicity tests in rats, mice and rabbits via dermal, intragastric, intraperitoneal, and inhalation routes of administration. Subchronic dermal toxicity of pyridosept was evaluated following cutaneous application for 90 days in rats and rabbits. Pyridosept was also examined in the accumulation test in rats and in micronucleus assay in the skin and bone marrow of mice after single and repeated administration. Acute oral toxicity study of pyridosept revealed an LD<sub>50</sub> of 1208 mg/kg in mice and 1242 mg/kg in rats, a dermal LD<sub>50</sub> > 2000 mg/kg in both species, and an LD<sub>50</sub> of 23-32 mg/kg upon intraperitoneal administration. In the 90-day dermal toxicity study in rats, no systemic toxicity was found; the only treatment-related effects were reversible local skin reactions at intermediate and high doses. In the 90-day rabbit study, dermatitis, granulomatous hepatitis, and mild interstitial nephritis occurred; however, the incidence of hepatitis did not differ significantly from the control and showed no dose dependence. In the skin accumulation study, the cumulation coefficient (Kk = 12.8) indicated no cumulative properties, and the micronucleus assay demonstrated no mutagenic activity in mouse skin or bone marrow. Pyridosept's acute toxicity upon oral administration is more favorable than that of benzalkonium chloride, comparable to miramistin, and slightly less favorable than chlorhexidine. The results of in vivo pharmacokinetic, allergenic, and immunotoxicity studies of pyridosept will be presented in forthcoming publications.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220385","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}
引用次数: 0
Emerging therapeutic role of cinnamic acid derivatives in hyperuricemia and gout: mechanistic, translational, and pharmacological perspectives. 肉桂酸衍生物在高尿酸血症和痛风中的新兴治疗作用:机制,翻译和药理学观点。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-19 DOI: 10.1007/s00210-026-06004-2
Shibanee Das, Reetuparna Acharya, Sanchit Suman Malik, Subarna Mahanti
{"title":"Emerging therapeutic role of cinnamic acid derivatives in hyperuricemia and gout: mechanistic, translational, and pharmacological perspectives.","authors":"Shibanee Das, Reetuparna Acharya, Sanchit Suman Malik, Subarna Mahanti","doi":"10.1007/s00210-026-06004-2","DOIUrl":"https://doi.org/10.1007/s00210-026-06004-2","url":null,"abstract":"<p><p>Hyperuricemia and gout are increasingly common metabolic and inflammatory disorders characterized by excessive accumulation of uric acid, impaired urate excretion, oxidative stress, and monosodium urate crystal inflammation. Although currently available therapies such as xanthine oxidase inhibitors and uricosuric agents effectively reduce serum levels of uric acid, their long-term clinical use is often associated with adverse reactions, limited tolerability, and incomplete disease management. As a result, there is increasing interest in identifying natural compounds that may serve as a potential preclinical lead for the development of more targeted urate-lowering strategies. Cinnamic acid derivatives, including p-coumaric acid, caffeic acid, ferulic acid, sinapic acid, chlorogenic acid, and synthetic analogs such as 4-nitrocinnamic acid, have shown promising anti-hyperuricemic and anti-gout activities in experimental studies. These compounds have pharmacological effects through several mechanisms, including the inhibition of xanthine oxidase; modulation of urate transporters such as URAT1, GLUT9, and ABCG2; suppression of inflammatory pathways including NF-κB and NLRP3 inflammasome signalling; antioxidant activity; and protection against renal injuries induced by uric acid. This review summarizes the molecular mechanisms, pharmacological evidence, and structure-activity relationships of selected cinnamic acid derivatives related to hyperuricemia and gout management. In addition, it discusses translational challenges associated with bioavailability, pharmacokinetics, toxicity evaluation, and clinical validation. Collectively, cinnamic acid derivatives represent promising pre-clinical leads that warrant further preclinical and clinical investigations to develop safer and more effective therapies against hyperuricemia and gout.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220400","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}
引用次数: 0
Gastrodin alleviates acute colitis with comorbid anxiety- and depression-like behaviours rather than cognitive dysfunction by modulating gut microbiota and suppressing inflammation. 天麻素通过调节肠道菌群和抑制炎症减轻急性结肠炎伴焦虑和抑郁样行为,而不是认知功能障碍。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-19 DOI: 10.1007/s00210-026-05930-5
Jia-Lin Song, Rui-Cong Wu, Rui Sun, Ya-Xin Gao, Bing-Qin He, Yan-Jie Xie, Jie-Shan Xie, Xi-Rui Li, Fei-Xiang Tong, Yan Liu, Hui Li, Zeng-Qin Wang
{"title":"Gastrodin alleviates acute colitis with comorbid anxiety- and depression-like behaviours rather than cognitive dysfunction by modulating gut microbiota and suppressing inflammation.","authors":"Jia-Lin Song, Rui-Cong Wu, Rui Sun, Ya-Xin Gao, Bing-Qin He, Yan-Jie Xie, Jie-Shan Xie, Xi-Rui Li, Fei-Xiang Tong, Yan Liu, Hui Li, Zeng-Qin Wang","doi":"10.1007/s00210-026-05930-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05930-5","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) patients frequently suffer from emotional disturbances, predominantly anxiety- and depression-like symptoms, and may also have cognitive dysfunction, but the mechanisms remain unclear, and no therapies targeting the gut or nervous system exist. Gastrodin (GAS), the primary active component of Gastrodia elata, has anti-inflammatory and neuroprotective effects. Whether GAS can alleviate acute colitis with comorbid anxiety- and depression-like behaviours or cognitive dysfunction via the gut-brain axis is unknown. Using a 3% dextran sulfate sodium (DSS)-induced mouse model, we administered GAS (240 mg/kg) by gavage for 7 days. The open field, elevated plus maze, tail suspension, and forced swimming tests showed that GAS improved behavioural abnormalities (including anxiety- and depression-like behaviours); it also restored colon length and reduced colonic histopathological injury. Metagenomic sequencing revealed that GAS reshaped the gut microbiota, increasing Sporosarcina and Nitrospirae while decreasing Clostridiaceae and Lachnospiraceae. Untargeted metabolomics indicated that GAS shifted the metabolic profile away from DSS and normalized taurine levels, and KEGG pathway analysis suggested that GAS may partially ameliorate DSS-induced metabolic disturbances by downregulating virulence-related pathways and upregulating energy metabolic pathways such as the TCA cycle and oxidative phosphorylation relative to DSS. Western blot confirmed that GAS restored the tight junction protein Occludin and decreased TNF-α. Quantitative proteomics demonstrated that GAS reversed the aberrant expression of 191 colonic proteins. These results demonstrate correlative associations between GAS treatment and the alleviation of acute colitis and behavioural abnormalities, alongside concurrent changes in gut microbiota composition, metabolite profiles, and intestinal barrier proteins. Whether these associations reflect a causal gut-brain axis mechanism requires direct experimental validation. GAS modulates the microbiota, partially restores metabolism, repairs the gut barrier, and suppresses local inflammation, suggesting a potential gut-brain axis mechanism. These findings position GAS as a promising candidate for further mechanistic and translational investigation in IBD-associated behavioural comorbidities.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220409","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}
引用次数: 0
Comparative hepatoprotective effects of Ginkgo biloba extract and N-Acetylcysteine against methotrexate-induced liver injury in rats: modulation of IκB-α, p38 MAPK, and p53 phosphorylation. 银杏叶提取物和n -乙酰半胱氨酸对甲氨蝶呤诱导大鼠肝损伤的肝保护作用:调节IκB-α、p38 MAPK和p53磷酸化。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-17 DOI: 10.1007/s00210-026-05973-8
Mohammed A Abdel-Rasol, Ruwaidah A R Abbas, Mohammed Y I Al-Hamadani, Wael M El-Sayed
{"title":"Comparative hepatoprotective effects of Ginkgo biloba extract and N-Acetylcysteine against methotrexate-induced liver injury in rats: modulation of IκB-α, p38 MAPK, and p53 phosphorylation.","authors":"Mohammed A Abdel-Rasol, Ruwaidah A R Abbas, Mohammed Y I Al-Hamadani, Wael M El-Sayed","doi":"10.1007/s00210-026-05973-8","DOIUrl":"https://doi.org/10.1007/s00210-026-05973-8","url":null,"abstract":"<p><p>Methotrexate (MTX) is an effective chemotherapeutic agent whose use can be limited by hepatotoxicity. This study comparatively evaluated the effects of Ginkgo biloba extract (GbE) and N-acetylcysteine (NAC) on MTX-induced liver injury, focusing on oxidative stress, inflammatory and apoptotic responses, and associated hepatic phosphorylation of Inhibitor of nuclear factor kappa-B alpha (IκB-α), p38 mitogen-activated protein kinase (p38 MAPK), and tumor protein p53 (p53), key components of stress-responsive signaling pathways. Thirty-two adult male rats were randomly assigned to four groups (n = 8/group). MTX (20 mg/kg, i.p.) was administered once on Day 4. GbE or NAC (200 mg/kg, p.o.) was administered for 3 days before and 6 days after MTX exposure. Serum alanine aminotransferase (ALT), total and direct bilirubin and hepatic malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor- alpha (TNF-α), interleukin-1 beta (IL-1β), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) were assessed. Hepatic phosphorylation of IκBα, p38 MAPK, and p53 was evaluated by Western blotting. MTX significantly (P < 0.001) increased serum ALT by 120% and hepatic MDA, TNF-α, IL-1β and Bax by 127%, 386%, 163%, and 439%, respectively, while reducing GSH and Bcl-2 by 66% and 63%, relative to control. Phosphorylation of IκBα, p38 MAPK, and p53 increased by 35%, 64%, and 68%, respectively. GbE and NAC significantly (P < 0.001) attenuated these alterations, with NAC producing generally greater effects than GbE. GbE and NAC attenuated MTX-induced hepatic injury across interconnected oxidative, inflammatory, apoptotic, and signaling endpoints. NAC showed a generally stronger response under the conditions tested. These findings support further investigation of both agents as potential strategies for mitigating MTX-associated hepatotoxicity.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207401","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}
引用次数: 0
PVA/chitosan-based hydrogels integrated with tilapia skin-derived collagen and Urtica dioica offers a promising approach for effective burn wound healing via transcriptional modulation of bFgf, Mmp2, Jak/Stat3, and α-Sma signaling pathway. PVA/壳聚糖为基础的水凝胶与罗非鱼皮肤源性胶原蛋白和枇杷结合,通过转录调节bFgf、Mmp2、Jak/Stat3和α-Sma信号通路,为烧伤创面的有效愈合提供了一种有前景的方法。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-17 DOI: 10.1007/s00210-026-05962-x
Aml Abdelnaby, Doaa H Assar, Abdallah S Salah, Mona Assas, Sara A Abdel Gaber, Ayman Atiba, Amany E Ragab, Ibrahim I Al-Hawary, Mustafa Shukry, Zizy I Elbialy
{"title":"PVA/chitosan-based hydrogels integrated with tilapia skin-derived collagen and Urtica dioica offers a promising approach for effective burn wound healing via transcriptional modulation of bFgf, Mmp2, Jak/Stat3, and α-Sma signaling pathway.","authors":"Aml Abdelnaby, Doaa H Assar, Abdallah S Salah, Mona Assas, Sara A Abdel Gaber, Ayman Atiba, Amany E Ragab, Ibrahim I Al-Hawary, Mustafa Shukry, Zizy I Elbialy","doi":"10.1007/s00210-026-05962-x","DOIUrl":"https://doi.org/10.1007/s00210-026-05962-x","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cutaneous wound repair is governed by a highly coordinated physiological cascade that includes recruitment of inflammatory cells, release of cytokine mediators, deposition of extracellular matrix components, and subsequent remodeling of scar tissue. Nowadays, plant extracts are viewed as an efficient alternative for wound healing. Urtica dioica (U. dioica) is rich in diverse bioactive plant compounds with varied therapeutic effects and appears to support skin wound repair. However, the molecular mechanisms and signaling pathways through which they influence regenerating tissues and cells remain poorly understood. This study aimed to confirm the signaling cascade and mechanism of topical application of a hydrogel formulation incorporated with tilapia (Oreochromis niloticus L.) skin-derived collagen and U. dioica extract on the skin regeneration process based on histopathological, TEM assessment as well as analyze alterations in the expression of key wound healing-related genes, such as Jak/Stat3, Smad3, fibroblast growth factor 2 (fgf2) genes, Acta2 ( α smooth muscle actin), and matrix metalloproteinases (Mmp2) gene in rat burn model. UPLC-ESI-MS/MS also analyzed the chemical composition of U. dioica. Thirty-five animals were randomly allocated to seven groups (n = 5 per group): negative control (NCtrl; no treatment), positive control (PCtrl), hydrogel base treated group (Hgb G), tilapia collagen hydrogel (ColHgb G), MEBO® cream (MEBO G), U. dioica extract (UD G), and a combination of collagen hydrogel plus U. dioica extract (ColHgb-UD G). Burn wound (2 × 2 cm) were made on the back of each generally anaesthetized rat, and wound surface area was measured on days 0, 3, 6, 9, 12, and 15 post-burn. The animals were then sacrificed, and tissues were collected for histological, TEM, and molecular analysis. Our results showed that the methanolic extract of the aerial parts of Urtica dioica was predominantly composed of flavonoids and fatty acids. Analysis in the negative ionization mode enabled the identification of several flavonoids, including apigenin, isorhamnetin, taxifolin, and eriodictyol, detected in both free and glycosylated forms. Wound closure was faster in the ColHgb-UD group than in the control-positive group. Gene expression patterns showed that U. dioica-treated rats, either alone or mixed with collagen hydrogel, notably inhibited the expression of profibrotic factors Jack/Stat3 and Acta2, while activating angiogenesis Fbgf2, Smad3 as well as Mmp2 compared with the positive control group. The histopathological findings showed significant healing progress in the ColHgb-UD group compared with the positive control untreated group and the other treated groups. Results demonstrate superior wound healing performance for ColHgb-UD compared to the control positive group the synergistic effect of U. dioica and collagen showed less scarring, more blood capillaries, less inflammatory cells therefore remarkably healed faster making the extract","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207419","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}
引用次数: 0
The dual role of the PI3K/AKT/mTOR axis in glial cell survival and neuroinflammation. PI3K/AKT/mTOR轴在胶质细胞存活和神经炎症中的双重作用。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-17 DOI: 10.1007/s00210-026-05986-3
Nourelhouda Neili, Aroua Jlassi, Sarra Hjaij, Ines Elbini
{"title":"The dual role of the PI3K/AKT/mTOR axis in glial cell survival and neuroinflammation.","authors":"Nourelhouda Neili, Aroua Jlassi, Sarra Hjaij, Ines Elbini","doi":"10.1007/s00210-026-05986-3","DOIUrl":"https://doi.org/10.1007/s00210-026-05986-3","url":null,"abstract":"<p><p>Multiple sclerosis is characterized by a triad of inflammation, demyelination, and neurodegeneration, yet current disease-modifying therapies are limited in their ability to halt progressive neurodegeneration or promote remyelination. The PI3K/AKT/mTOR signaling pathway is a master regulator of these divergent cellular processes and therefore represents a biological paradox in multiple sclerosis. In the pathogenic facet of the disease, activation of this axis supports the differentiation and effector functions of pro-inflammatory T- and B-cells and contributes to inflammatory programs in microglia and macrophages. In the regenerative facet, physiological PI3K/AKT/mTOR activity is required for oligodendrocyte precursor-cell survival, differentiation, myelin synthesis, and maintenance of myelin integrity. Astrocytic signaling adds another layer of context-dependence, with pathway activity influencing reactive gliosis and the inflammatory or reparative properties of the lesion environment. Consequently, systemic inhibition of the pathway may suppress neuroinflammation while simultaneously interfering with endogenous repair. This review therefore considers PI3K/AKT/mTOR axis according to these opposing pathogenic and protective functions, highlighting the importance of cell type, disease stage, and treatment timing. Precision strategies capable of selectively suppressing inflammatory signaling while preserving or restoring pro-regenerative activity, potentially through cell-specific molecular targets, may provide a more rational therapeutic approach than generalized pathway inhibition.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207373","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}
引用次数: 0
Delta-9-tetrahydrocannabinol ameliorates oxidative stress, mitochondrial redox state, and neuroinflammation induced by high-fructose diet. δ -9-四氢大麻酚可改善高果糖饮食诱导的氧化应激、线粒体氧化还原状态和神经炎症。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-17 DOI: 10.1007/s00210-026-05991-6
Muhammet Sait Toprak, Zeynep Mine Coskun Yazici, Karolin Yanar, Sema Bolkent
{"title":"Delta-9-tetrahydrocannabinol ameliorates oxidative stress, mitochondrial redox state, and neuroinflammation induced by high-fructose diet.","authors":"Muhammet Sait Toprak, Zeynep Mine Coskun Yazici, Karolin Yanar, Sema Bolkent","doi":"10.1007/s00210-026-05991-6","DOIUrl":"https://doi.org/10.1007/s00210-026-05991-6","url":null,"abstract":"<p><p>This study investigates the effects of a high-fructose diet (HFD) on brain oxidative stress, mitochondrial redox state, and pro-inflammatory cytokine expression, and specifically evaluates whether delta-9-tetrahydrocannabinol (THC) attenuates these HFD-induced changes. Thirty-two Sprague-Dawley rats were divided into four groups: Control, HFD (10% fructose in drinking water for 12 weeks), THC (1.5 mg/kg daily for the last 4 weeks), and HFD + THC (HFD for 12 weeks with THC co-administration during the final 4 weeks). Biochemical biomarkers (AOPP, DT, KYN, MDA, AGE, T-SH, NADH, FAD, serotonin, insulin) and mRNA expression levels of inflammation-related genes (IL-6, IL-1β, TNF-α, NF-κB) were analyzed in brain tissues. The HFD significantly increased levels of protein oxidation (AOPP, DT, KYN, AGE); lipid peroxidation (MDA); and NADH and FAD fluorescence whilst decreasing total thiol (T-SH) content. HFD also increased the mRNA expression of all inflammatory markers examined. In contrast, THC treatment significantly reduced oxidative damage and NADH and FAD fluorescence and reduced the relative mRNA expression of the investigated inflammation-related genes. Strong positive correlations were observed between pro-inflammatory cytokine mRNA expression and oxidative stress markers. HFD causes significant biochemical and molecular damage to the brain. THC administration was associated with a significant attenuation of HFD-induced oxidative stress, mitochondrial redox state, and pro-inflammatory cytokine expression, suggesting that it may mitigate diet-associated neurochemical perturbations.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207336","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}
引用次数: 0
Identification of a novel Microbacterium species and biosynthesis of gold nanoparticles: activation of apoptosis and dysregulation of ABCG transporters in gastric adenocarcinoma cells. 一种新型微细菌的鉴定和金纳米颗粒的生物合成:胃腺癌细胞中凋亡的激活和ABCG转运蛋白的失调。
IF 4 4区 医学
Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2026-10-17 DOI: 10.1007/s00210-026-06011-3
Md Amdadul Huq, Sricharan Dhandapani, Abdus Samad, Shahina Akter, Yeon-Ju Kim
{"title":"Identification of a novel Microbacterium species and biosynthesis of gold nanoparticles: activation of apoptosis and dysregulation of ABCG transporters in gastric adenocarcinoma cells.","authors":"Md Amdadul Huq, Sricharan Dhandapani, Abdus Samad, Shahina Akter, Yeon-Ju Kim","doi":"10.1007/s00210-026-06011-3","DOIUrl":"https://doi.org/10.1007/s00210-026-06011-3","url":null,"abstract":"<p><p>Gastric cancer has high morbidity and mortality rates worldwide, often requiring new therapeutic approaches. Biosynthesis of gold nanoparticles (GNPs) offers a promising treatment due to their unique biological properties and biocompatibility. In this study, we synthesized gold nanoparticles using the cultural supernatant of Microbacterium sp. MAH-37 (MM37-S) and evaluated their anti-gastric cancer activity, focusing on apoptosis induction and regulation of the ABCG transporter pathway. The Microbacterium sp. strain MAH-37 was isolated from pumpkin garden soil, and its morphology was characterized by transmission electron microscopy (TEM). The successful biosynthesis of MM37-S-GNP was confirmed by UV-visible spectroscopy, SAED, DLS, FTIR, XRD, EDX, and FE-TEM analyses. Biological evaluations revealed that MM37-S-GNPs exhibited cytotoxicity of approximately 72% at 200 µg/mL against AGS cells and confirmed by colony formation and Live/Dead assay, whereas normal HFE-145 cells was non-toxic. Furthermore, Hoechst 33,258, propidium iodide, and Mito Tracker revealed nuclear condensation and fragmentation, membrane-compromised cells, and mitochondrial disruption, respectively, indicating cell death via apoptosis. H<sub>2</sub>DCFDA staining demonstrated a significant increase intracellular reactive oxygen species (ROS) generation in AGS cells following MM37-S-GNP. Flow cytometric analysis revealed that treatment induced apoptosis in AGS cells, with 30.4% apoptotic cells observed at 200 µg/mL. Consistently, mRNA and protein expression levels confirmed apoptosis cell death, as evidenced by an increased Bax/Bcl-2 ratio and elevated levels of cleaved caspase-9. Additionally, Western blot analysis revealed that treatment with higher doses of MM37-S-GNPs significantly downregulated the expression of ABCG1 and ABCG2 transporters. MM37-S-GNPs selectivelyeliminated gastric cancer cells through ROS-mediated mitochondrial damage and apoptotic pathways, while effectively regulating ABCG transporter expression, highlighting their potential as a promising nanotherapeutic agent.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207404","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}
引用次数: 0
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