European journal of pharmacology最新文献

{"title":"N-(4-methoxyphenyl) quinoline-8-sulfonamide reduces the inflammatory response of fibroblast-like synoviocytes by targeting receptor (calcitonin) activity modifying protein 1 in rheumatoid arthritis","authors":"Ying-Li Yang ,&nbsp;Ning Yao ,&nbsp;Shang-Qing Ge ,&nbsp;Biao Song ,&nbsp;Han Xu ,&nbsp;Zeng Li ,&nbsp;Xiao-Feng Li ,&nbsp;Jun Li","doi":"10.1016/j.ejphar.2024.177064","DOIUrl":"10.1016/j.ejphar.2024.177064","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovium of joints. Fibroblast-like synoviocytes (FLS) play an important role in RA pathogenesis. We aimed to investigate the effect of N-(4-methoxyphenyl) quinoline-8-sulfonamide (QS-3g) on the inflammatory response of FLS and explore the potential underlying mechanisms.</div></div><div><h3>Methods</h3><div>We screened and found that QS-3g exhibits the best anti-inflammatory response against FLS using the CCK8 assay. To investigate the therapeutic effects of QS-3g on K/BxN STA mice, we used H&amp;E staining, immunofluorescence, immunohistochemistry, micro-CT, and other techniques. Additional investigations, including RNA-seq, molecular docking, and CETSA, revealed that QS-3g binds to RAMP1.</div></div><div><h3>Results</h3><div>Among a series of 8-quinoline sulfonyl amide derivatives, QS-3g reduced the inflammatory response in TNF-α stimulated FLS, such as the release of interleukin (IL)-1β and IL-6. H&amp;E staining and micro-CT showed that QS-3g inhibited synovial hypertrophy, inflammatory cell infiltration, and bone destruction. RNA-seq and CETSA analyses revealed the targeted inhibition of RAMP1 by QS-3g. Inhibition of RAMP1 expression could reduce IL-6 and IL-1β levels. Compared with RAMP1-si, combined administration of QS-3g and RAMP1-si reduced the TNF-α-induced inflammation in TNF-α stimulated FLS without statistically significant differences. Finally, the results of <em>in vitro</em> experiments showed that QS-3g could restore the balance of Gαi/Gαs by inhibiting Gαi and activating Gαs and up-regulate the expression of cAMP protein, thus inhibiting the RAMP1-mediated inflammatory response in FLS.</div></div><div><h3>Conclusion</h3><div>QS-3g could inhibit RAMP1 activity and mediate the Gαs/Gαi–cAMP pathway to reduce FLS inflammatory response. Therefore, QS-3g may serve as a novel anti-inflammatory compound for treating RA.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177064"},"PeriodicalIF":4.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escin ameliorates CUMS-induced depressive-like behavior via BDNF/TrkB/CREB and TLR4/MyD88/NF-κB signaling pathways in rats","authors":"Fengjiao Liu ,&nbsp;Yaxin Jia ,&nbsp;Liwei Zhao ,&nbsp;Li-na Xiao ,&nbsp;Xizhen Cheng ,&nbsp;Yingying Xiao ,&nbsp;Ying Zhang ,&nbsp;Yuling Zhang ,&nbsp;Huimin Yu ,&nbsp;Qiao-en Deng ,&nbsp;Yuanyuan Zhang ,&nbsp;Yimeng Feng ,&nbsp;junfang Wang ,&nbsp;Yonggang Gao ,&nbsp;Xuan Zhang ,&nbsp;Yunyun Geng","doi":"10.1016/j.ejphar.2024.177063","DOIUrl":"10.1016/j.ejphar.2024.177063","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with brain inflammation and neuronal damage. Derived from the <em>Aesculus chinensis Bunge</em> fruit, escin has shown anti-inflammatory and neuroprotective effects. However, its potential as a treatment for MDD is unclear. This study investigates the antidepressant properties of escin using in vivo experimentation. The chronic unpredictable mild stress (CUMS) model was used to analyze the potential antidepressant effects and underlying mechanisms of escin. Wistar rats were exposed to CUMS for 35 consecutive days to induce MDD. The rats were then given either escin (1, 3, and 10 mg/kg) or fluoxetine (2 mg/kg) on a daily basis. Notably, escin significantly alleviated the depressive behaviors induced by CUMS, as evaluated through a series of behavioral assessments. Moreover, escin administration reduced TNF-α, IL-1β, and IL-6 levels in the hippocampus. It also decreased serum adrenal cortical hormone (ACTH) and corticosterone (CORT) levels while increasing 5-HT and Brain-derived neurotrophic factor (BDNF) levels in the CUMS rats, as measured by the enzyme-linked immunosorbent assay (ELISA). Pathological changes in the hippocampal regions were identified through Nissl staining, and Western blotting was used to quantify the protein levels of BDNF, TrkB, CREB, TLR4, MyD88, and NF-κB. Escin mitigated neuronal injury, elevated TrkB, BDNF, and CREB, and reduced TLR4, MyD88, and NF-κB protein levels in CUMS rats. The data from this study suggest that escin holds the potential for alleviating depression-like symptoms induced by CUMS. This effect may be mediated through the modulation of two signaling pathways, BDNF/TrkB/CREB and TLR4/MyD88/NF-κB.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177063"},"PeriodicalIF":4.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longikaurin A induces ferroptosis and inhibits glioblastoma progression through DNA methylation - Mediated GPX4 suppression","authors":"Xiangrui Meng ,&nbsp;Qingqing Yang ,&nbsp;Yisu Gao ,&nbsp;Yawei Liu ,&nbsp;Fang Chen ,&nbsp;Wangsen Cao ,&nbsp;Guan Sun","doi":"10.1016/j.ejphar.2024.177061","DOIUrl":"10.1016/j.ejphar.2024.177061","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most common primary intracranial tumor highly resistant to conventional clinical chemotherapy. Recently, the induction of ferroptosis is emerging as a putative strategy to treat various tumors. However, the identification of the effective and applicable tumor ferroptosis-inducing agents remains challenging. In this study, we showed that longikaurin A (LK-A), a natural diterpenoid isolated from the medicinal plant Isodon ternifolius with strong anti-GBM capacities, induced remarkable GBM cell ferroptosis along with suppressing the key anti-ferroptosis factor glutathione peroxidase 4 (GPX4). GPX4 promoter contains conserved CpG islands. The LK-A-induced GPX4 suppression coincided with the inhibition of ten-eleven translocation 2 (TET2), a key DNA demethylation enzyme and an increase in the hypermethylation of the GPX4 promoter. Further, LK-A promoted the GBM ferroptotic alterations and inhibited GBM progression in both subcutaneous and orthotopic xenograft mouse models, whereas GPX4 overexpression largely abrogated its anti-GBM effects both in vitro and <em>in vivo</em>, suggesting that LK-A inductions of the DNA methylation-incurred GPX4 suppression and ferroptosis are crucial for its anti-GBM functions. Together, our study has elaborated an important epigenetic pathway of GBM ferroptosis and uncovered a critical pharmacological property of LK-A for treating GBM patients.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177061"},"PeriodicalIF":4.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium nitrite induces tolerance in the mouse aorta: Involvement of the renin-angiotensin system, nitric oxide synthase, and reactive oxygen species","authors":"Natalia Ferreira de Araujo ,&nbsp;Natalia Ribeiro Cabacinha Nobrega ,&nbsp;Daniela Esteves Ferreira dos Reis Costa ,&nbsp;Janaina Aparecida Simplicio ,&nbsp;Naiara de Assis Rabelo Ribeiro ,&nbsp;Carlos Renato Tirapelli ,&nbsp;Daniella Bonaventura","doi":"10.1016/j.ejphar.2024.177056","DOIUrl":"10.1016/j.ejphar.2024.177056","url":null,"abstract":"<div><div>Nitrites have emerged as promising therapeutic agents for cardiovascular diseases, alongside nitrates. While chronic use of organic nitrates is well recognized to lead to vascular tolerance, the tolerance associated with nitrite therapy remains incompletely understood. The aim of the present study was to investigate vascular tolerance to sodium nitrite and the underlying molecular mechanisms. Endothelium-denuded aortic rings isolated from male Balb/C mice were incubated with either the EC₅₀ (10⁻⁴ mol/L) or EC₁₀₀ (10⁻² mol/L) concentration of sodium nitrite for 15 min to induce tolerance. The EC₁₀₀ concentration of sodium nitrite induced vascular tolerance. Pre-incubation with captopril and losartan effectively reversed sodium nitrite-induced tolerance. Similarly, pre-incubation with L-NAME and L-arginine prevented sodium nitrite-induced tolerance. Increased levels of reactive oxidative species (ROS) and reduced bioavailability of nitric oxide (NO) were observed in tolerant aortas. Increased superoxide dismutase (SOD) activity and decreased catalase activity were also verified in tolerant aortas. Both captopril and L-NAME prevented the increased levels of ROS observed in tolerant aortas. Furthermore, pre-incubation with catalase effectively prevented sodium nitrite-induced tolerance. Our findings suggest that sodium nitrite induces vascular tolerance through a signaling pathway involving the renin-angiotensin system, nitric oxide synthase, and ROS. This study contributes to the understanding of the interaction between nitrites and vascular tolerance and highlights potential targets to overcome or prevent this phenomenon.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177056"},"PeriodicalIF":4.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel prospects in targeting neurodegenerative disorders via autophagy","authors":"Shumayila Khan ,&nbsp;Saurabh Upadhyay ,&nbsp;Md. Imtaiyaz Hassan","doi":"10.1016/j.ejphar.2024.177060","DOIUrl":"10.1016/j.ejphar.2024.177060","url":null,"abstract":"<div><div>Protein aggregation occurs as a consequence of dysfunction in the normal cellular proteostasis, which leads to the accumulation of toxic fibrillar aggregates of certain proteins in the cell. Enhancing the activity of proteolytic pathways may serve as a way of clearing these aggregates in a cell, and consequently, autophagy has surfaced as a promising target for the treatment of neurodegenerative disorders. Several strategies involving small molecule compounds that stimulate autophagic pathway of cell have been discovered. However, despite many compounds having demonstrated favorable outcomes in experimental disease models, the translation of these findings into clinical benefits for patient's remains limited. Consequently, alternative strategies are actively being explored to effectively target neurodegeneration via autophagy modulation. Recently, newer approaches such as modulation of expression of autophagic genes have emerged as novel and interesting areas of research in this field, which hold promising potential in neuroprotection. Similarly, as discussed for the first time in this review, the use of autophagy-inducing nanoparticles by utilizing their physicochemical properties to stimulate the autophagic process, rather than relying on their role as drug carriers, offers a completely fresh avenue for targeting neurodegeneration without the risk of drug-associated adverse effects. This review provides fresh perspectives on developing autophagy-targeted therapies for neurodegenerative disorders. Additionally, it discusses the challenges and impediments of implementing these strategies to alleviate the pathogenesis of neurodegenerative disorders in clinical settings and highlights the prospects and directions of future research in this context.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177060"},"PeriodicalIF":4.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polarized macrophage functions are affected differentially after CSF-1R inhibition with PLX5622","authors":"Julia Barilo,&nbsp;Nasry Zane Bouzeineddine,&nbsp;Alecco Philippi,&nbsp;Sam Basta","doi":"10.1016/j.ejphar.2024.177059","DOIUrl":"10.1016/j.ejphar.2024.177059","url":null,"abstract":"<div><div>PLX5622 is a colony stimulating factor 1 receptor (CSF-1R) inhibitor that is known to deplete microglial cells <em>in vivo</em>. Recently its effects on macrophages (Mφ) were also observed <em>in vivo</em>. Therefore, we performed this study to assess its <em>in vitro</em> effects on the differentiation and functions of polarized Mφ derived from different tissues. Our findings show that addition of PLX5622 early on after <em>ex vivo</em> isolation hinders Mφ differentiation and survival. However, its addition post Mφ differentiation did not significantly affect the viability. Furthermore, PLX5622 affects certain functions and degree of polarization of IL-4 (M2a) Mφ but not polarization of M1-like Mφ. Our study provides novel aspects on the application of PLX5622 to study Mφ functions <em>in vitro</em>, where polarization is affected by CSF-1R signalling and provides distinctive evidence to its ability to affect certain populations of Mφ during <em>in vitro</em> differentiation and maturation.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177059"},"PeriodicalIF":4.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose treatment with Epirubicin, a novel histone deacetylase 1 inhibitor, exerts anti-leukemic effects by inducing ferroptosis","authors":"Guancui Yang ,&nbsp;Shijie Yang ,&nbsp;Jiarun Li ,&nbsp;Peijie Jiang ,&nbsp;Xiaolong Tian ,&nbsp;Xiaoqi Wang ,&nbsp;Jin Wei ,&nbsp;Xi Zhang ,&nbsp;Jinyi Liu","doi":"10.1016/j.ejphar.2024.177058","DOIUrl":"10.1016/j.ejphar.2024.177058","url":null,"abstract":"<div><h3>Aims</h3><div>Leukemia is hematopoietic stem cell malignant tumor with poor outcomes. Histone deacetylase 1 (HDAC1) is highly expressed in leukemia and current HDAC1 inhibitors have clinical limitations in leukemia therapy. Therefore, novel HDAC1 inhibitor is imperative to being found and its mechanism needs to be further explored.</div></div><div><h3>Materials and methods</h3><div>Novel HDAC1 inhibitors were discovered through drug virtual screening. CCK-8, EdU and soft agar assay were used to assess the anti-leukemic effect of the candidate HDAC1 inhibitor. ROS, lipid peroxidation, intracellular Fe²⁺ and LIP assay were employed to verify cell ferroptosis. Additionally, a xenograft model was performed to explore the efficacy and safety of the candidate HDAC1 inhibitor in vivo.</div></div><div><h3>Results</h3><div>HDAC1 might be a promising therapeutic target for leukemia and Epirubicin (Epi) could be used as a potential HDAC1 inhibitor. Low-dose Epi exhibited good anti-leukemic effects by inhibiting cell proliferation, DNA synthesis and colony formation. Low-dose Epi could induce ferroptosis by triggering lipid peroxidation, which was better than that treated with current HDAC1 inhibitors Chidamide or Vorinostat, ROS generation and Fe²⁺ overload in leukemia cells. Mechanistically, low-dose Epi induced ferroptosis by targeting amino acid metabolism and iron metabolism. Similar results were found in a xenograft model in NOG mice with a good safety profile.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that Epi might be used as a HDAC1 inhibitor. Low-dose Epi could inhibit tumor progression by inducing cell ferroptosis in vitro and in vivo. Thus, Epi administration with lower concentration may be much more favorable and safer in the treatment with leukemia.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177058"},"PeriodicalIF":4.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Captopril inhibits the overproduction of proopiomelanocortin and adrenocorticotropic hormone in the pituitary gland of male diabetic mice in close relationship with an increase in glucocorticoid receptor expression","authors":"Amanda da Silva Chaves ,&nbsp;Nathalia Santos Magalhães ,&nbsp;Daniella Bianchi Reis Insuela ,&nbsp;Patrícia Machado Rodrigues e Silva ,&nbsp;Marco Aurélio Martins ,&nbsp;Vinicius Frias Carvalho","doi":"10.1016/j.ejphar.2024.177057","DOIUrl":"10.1016/j.ejphar.2024.177057","url":null,"abstract":"<div><div>Prior investigation shows that diabetic patients present hypothalamus-pituitary-adrenal (HPA) axis hyperactivity related to impaired negative feedback. This study investigates the effect of Captopril on the overproduction of adrenocorticotropic hormone (ACTH) and its precursor proopiomelanocortin (POMC) in the pituitary gland of male diabetic mice. Diabetes was induced by intravenous injection of alloxan into fasted Swiss-webster mice, and the animals were treated with Captopril for 14 consecutive days, starting 7 days post-diabetes induction. Plasma corticosterone levels were evaluated by ELISA, while pituitary gland expressions of angiotensin-II type 1 receptor (AT₁), angiotensin-II type 2 receptor (AT₂), ACTH, Bax, Bcl-2, KI-67, POMC, and glucocorticoid receptor (GR) were evaluated using immunohistochemistry or Western blot. Diabetic mice showed pituitary gland overexpression of AT₁, without altering AT₂ levels, which were sensitive to Captopril treatment. Furthermore, diabetic mice presented hypercortisolism, along with an increase in the number of corticotroph cells, POMC and ACTH expression, and number of proliferative cells, and a decrease of GR expression in the pituitary gland. In addition, treatment with Captopril reduced systemic corticosterone levels, corticotroph and proliferative cell numbers, and Bcl-2, POMC, and ACTH expression in the pituitary gland of diabetic mice, besides increasing the expression of Bax and GR. In conclusion, these findings show that Captopril is a promising therapy for treating complications associated with HPA axis hyperactivity in diabetic patients, in a mechanism probably related to the downregulation of POMC production in the pituitary gland and subsequent reduction of systemic corticosterone levels.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177057"},"PeriodicalIF":4.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of neonatal hyperoxia on adult cardiac autonomic function in rats: Role of angiotensin II type 1 receptor activation","authors":"Jéssica Hellen Poletto Bonetto ,&nbsp;Alyson Deprez ,&nbsp;Daniele Wolf ,&nbsp;Rafael Oliveira Fernandes ,&nbsp;Karina Casali ,&nbsp;Aurélie Sonea ,&nbsp;Adrien Flahault ,&nbsp;Marina Siqueira Flores ,&nbsp;Ying He ,&nbsp;Adriane Belló-Klein ,&nbsp;Daniela Ravizzoni Dartora ,&nbsp;Anne Monique Nuyt","doi":"10.1016/j.ejphar.2024.177026","DOIUrl":"10.1016/j.ejphar.2024.177026","url":null,"abstract":"<div><div>Individuals born preterm present altered cardiac autonomic function, a risk factor to heart diseases. Neonatal renin-angiotensin-system activation contributes to adult cardiomyopathy in rats exposed to neonatal hyperoxia, a well-established model of preterm birth-related conditions. Central angiotensin II receptor activation is a key modulator of the autonomic drive to the heart. Whether neonatal hyperoxia leads to alteration of the cardiac autonomic function through activation of the angiotensin II receptor type 1 (AT1) is unknown and was examined in the present study.</div><div>Sprague-Dawley pups were exposed to hyperoxia or room air from postnatal days 3–10. AT1 antagonist losartan or water was given orally postnatal days 8–10. Blood pressure, autonomic function, left ventricular sympathetic innervation, β-adrenergic-receptors expression, and AT1 expression in the solitary-tract-nucleus were examined in adult rats.</div><div>Neonatal hyperoxia led to loss of day-night blood pressure variation, decreased heart rate variability, increased sympathovagal balance, increased AT1 expression in the solitary-tract, decreased left ventricle sympathetic innervation, and increased β1-adrenergic-receptor protein expression. Losartan prevented the autonomic changes and AT1 expression in the solitary-tract but did not impact the loss of circadian blood pressure variation nor the changes in sympathetic innervation and in β1-adrenergic-receptor expression.</div><div>In conclusion, neonatal hyperoxia leads to both central autonomic and cardiac sympathetic changes, partly programmed by neonatal activation of the renin-angiotensin system.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177026"},"PeriodicalIF":4.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-nociceptive effects of non-antibiotic derivatives of demeclocycline and doxycycline against formalin-induced pain stimulation","authors":"Glauce Crivelaro Nascimento ,&nbsp;Airam Nicole Vivanco-Estela ,&nbsp;Laurent Ferrié ,&nbsp;Bruno Figadere ,&nbsp;Rita Raisman-Vozari ,&nbsp;Patrick Pierre Michel ,&nbsp;Elaine Del Bel","doi":"10.1016/j.ejphar.2024.177054","DOIUrl":"10.1016/j.ejphar.2024.177054","url":null,"abstract":"<div><div>In previous studies, some tetracycline (TC) antibiotics showed potential as analgesic. We investigated here the analgesic activity of new non-antibiotic TC derivatives using the formalin-induced nociceptive pain model in adult C57BL/6 mice. Specifically, we tested the effects of i.p. injections of DDMC (5, 10, 20 mg kg⁻¹) and DDOX (10, 20, 40 mg kg⁻¹), which are non-antibiotic derivatives of demeclocycline and doxycycline, respectively. Repeated treatments with DDMC remarkably reduced nociceptive pain in both phases of the test, at 10 mg kg⁻¹ its efficacy was comparable to that of 10 mg kg⁻¹ of morphine. DDOX was also effective in this paradigm but intrinsically less potent than DDMC, exerting analgesic effects between 20 and 40 mg kg⁻¹. Interestingly, a single injection of DDMC (10 mg kg⁻¹) was sufficient to produce a robust anti-nociceptive effect similar to that of morphine. A single injection of DDOX (40 mg kg⁻¹) also produced anti-nociceptive effects but only in the second phase of the test. Noticeably, male mice exhibited a better analgesic response to DDMC (10 mg kg⁻¹) than females. A single injection of DDMC (10 mg kg⁻¹) and morphine but not of DDOX (40 mg kg⁻¹), powerfully inhibited formalin-induced spinal cord c-Fos expression whereas both TC derivatives restrained the activation of Iba-1-immunoreactive cells, indicating a potential indirect effect on inflamed microglial cells. In summary, the non-antibiotic TCs, DDMC and DDOX, demonstrated notable analgesic efficacy against formalin-induced pain, suggesting their potential as alternatives for analgesic treatment.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177054"},"PeriodicalIF":4.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}