Frontiers in Pharmacology最新文献

{"title":"<i>Lycium barbarum</i> L.: a potential botanical drug for preventing and treating retinal cell apoptosis.","authors":"Meng Xiong, Jun Peng, Shunhua Zhou, Qing Gao, Jing Lu, Chen Ou, Houpan Song, Qinghua Peng","doi":"10.3389/fphar.2025.1571554","DOIUrl":"10.3389/fphar.2025.1571554","url":null,"abstract":"<p><p>Retinal cell apoptosis is the primary pathological process in many retinal diseases, including retinitis pigmentosa and age-related macular degeneration, which can cause severe visual impairment and blindness. <i>Lycium barbarum L.</i>, a traditional Chinese medicinal botanical drug, has a long history and extensive application in ophthalmic disease prevention and treatment. This study systematically reviewed the key active metabolites in <i>L. barbarum L.,</i> including <i>L. barbarum</i> polysaccharides, carotenoids, and flavonoids, that exert retinal protective effects. A comprehensive analysis of the pharmacological effects and underlying molecular mechanisms of <i>L. barbarum L.</i> and its active metabolites in the prevention and treatment of retinal cell apoptosis, including essential aspects such as antioxidant activity, anti-inflammatory properties, autophagy regulation, and mitochondrial function preservation, is essential to establish a comprehensive and solid theoretical basis for further investigation of the medicinal value of <i>L. barbarum L.</i> in ophthalmology and provide a reference for future research directions.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1571554"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide attenuates myocardial ischemia-reperfusion injury by inhibiting ferroptosis of cardiomyocytes via activation of PKC-S100A9 axis.","authors":"Yan Liu, Zixuan Li, Xinhe Xu, Yan Zou, Miaomiao Zhang, Yingyu Chen, Wenwu Zhu, Bing Han","doi":"10.3389/fphar.2025.1529652","DOIUrl":"10.3389/fphar.2025.1529652","url":null,"abstract":"<p><strong>Objective: </strong>The incidence of ischemic cardiomyopathy increases annually worldwide, and it is the leading cause of mortality in China. Although interventional diagnostic and therapeutic techniques can promptly open the culprit vessels, myocardial ischemia-reperfusion injury (MIRI), resulting from restored blood flow, is often inevitable. Semaglutide (Sem), a novel GLP-1 analogue, is primarily utilized in managing Type 2 diabetes mellitus (T2DM). Recent research indicates that semaglutide may reduce the risk of major adverse cardiovascular events. Therefore, the purpose of this study is to explore whether semaglutide can ameliorate MIRI and explore its potential mechanism.</p><p><strong>Methods and results: </strong>: A mouse model of myocardial ischemia-reperfusion (I/R) was created by ligating the left anterior descending coronary artery (LAD) first for 45 min and then reperfusing the heart for 24 h. Assessment of cardiac function and fibrosis were conducted through small animal ultrasound and Masson's staining. It was observed that semaglutide enhanced cardiac function recovery and diminished fibrosis in the I/R model. <i>In vivo</i> experiments, semaglutide proved to mitigate oxidative stress and inhibit ferroptosis in cardiomyocytes. RNA sequencing showed that S100 calcium binding protein A9 (S100A9) was the target gene of semaglutide to protect against MIRI. <i>In vitro</i>, experiments showed that semaglutide decreased the expression of S100A9 by activating the Protein Kinase C(PKC) pathway, thus inhibiting ferroptosis in cardiomyocytes.</p><p><strong>Conclusion: </strong>Semaglutide can reduce I/R-induced myocardial injury by inhibiting the ferroptosis of cardiomyocytes. In the mechanism, semaglutide mainly reduce the expression of S100A9 via the activation of PKC signaling pathway. Therefore, semaglutide is considered as a potential treatment option for MIRI.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1529652"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer.","authors":"Lu Liu, Bing Wang, Xiaoya Ma, Lei Tan, Xudong Wei","doi":"10.3389/fphar.2025.1513948","DOIUrl":"10.3389/fphar.2025.1513948","url":null,"abstract":"<p><strong>Background: </strong>Laryngeal cancer (LC) is characterized by high mortality and remains challenging in prognostic evaluation and treatment benefits. Ubiquitin-related genes (UbRGs) are widely involved in cancer initiation and progression, but their potential value in LC is unknown.</p><p><strong>Methods: </strong>RNA-seq and clinical data of LC were obtained from TCGA and GEO. UbRGs that independently influenced the overall survival (OS) of LC patients were screened with differential expression, COX and LASSO regression analyses. A prognostic signature was then established and assessed for its predictive value, stability and applicability using Kaplan-Meier analysis and receiver operating characteristic curves. The nomogram was further generated in combination with the signature and clinical characteristics. Characterization of immune properties and prediction of drug sensitivity were investigated on the signature-based subgroups using a panel of <i>in silico</i> platforms. Verification of gene expression was conducted with Western blot, qRT-PCR and ELISA, ultimately.</p><p><strong>Results: </strong>PPARG, LCK and LHX1 were identified and employed to construct the UbRGs-based prognostic signature, showing a strong ability to discriminate LC patients with distinct OS in TCGA-LC and GSE65858, and excellent applicability in most clinical conditions. The nomogram showed higher predictive value and net clinical benefit than traditional indicators. As evaluated, the low-risk group had a more activated immune function, higher infiltration of anti-cancer immune cells and stronger expression of immune-promoting cytokines than the high-risk group. Immune properties were also correlated with individual signature genes. PPARG and LHX1 were negatively correlated, whereas LCK positively correlated, with the immuno-promoting microenvironment. Additionally, chemotherapy would be more effective in high-risk patients, while immune checkpoint inhibitors would be more effective in low-risk patients. Finally, dysregulation of the signature genes was confirmed in LC cell lines by Western blot, and PPARG knockdown significantly reduced the expression of the immunosuppressive cytokines IL6, TGFB1, TGFB2 and VEGFC by qRT-PCR and ELISA.</p><p><strong>Conclusion: </strong>We have developed a UbRGs-based signature for LC prognostic evaluation that is valuable in clinical application, indicative of the immune microenvironment and beneficial for individualized treatment guidance.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1513948"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isobavachalcone ameliorates Alzheimer disease pathology by autophagy-mediated clearance of amyloid beta and inhibition of NLRP3 inflammasome in primary astrocytes and 5x-FAD mice.","authors":"Dilpreet Kour, Parul Khajuria, Kuhu Sharma, Alpa Sharma, Ankita Sharma, Syed Mudassir Ali, Priya Wazir, P Ramajayan, Sanghapal D Sawant, Utpal Nandi, Zabeer Ahmed, Ajay Kumar","doi":"10.3389/fphar.2025.1525364","DOIUrl":"10.3389/fphar.2025.1525364","url":null,"abstract":"<p><strong>Background and aim: </strong>Alzheimer's disease (AD) progresses with Aβ plaque deposition and neuroinflammation. Given the complexity of AD pathology, single-target therapies have frequently failed in clinical trials. We hypothesized that a multitarget approach could yield better therapeutic outcomes. To this end, we identified isobavachalcone (IBC), a natural compound with dual pharmacological activity in reducing Aβ plaques and neuroinflammation.</p><p><strong>Experimental procedure: </strong>Primary astrocytes were isolated from 3 to 4 days old C57BL/6J mice pups for <i>in-vitro</i> assays, while <i>in-vivo</i> studies were conducted on 5x-FAD mice. Protein alterations were evaluated using ELISA, western blotting, immunocytochemistry, and immunohistochemistry. Behavioral analyses included the radial arm maze, open field, and rotarod tests. Data from all <i>in vitro</i> and <i>in vivo</i> experiments were analyzed by using one-way ANOVA and <i>post-hoc</i> Bonferroni tests.</p><p><strong>Results: </strong><i>In-vitro</i> analyses in astrocytes demonstrated that IBC at 5 and 10 μM concentrations induce AMPK phosphorylation through CAMKK2, promoting autophagy and inhibiting the NLRP3 inflammasome in primary astrocytes. IBC-treated astrocytes exhibited significant clearance of extracellular amyloid beta. Mechanistic studies highlighted autophagy as a key factor in reducing both NLRP3 inflammasome activity and Aβ levels. Two months of treatment of 5x-FAD mice with IBC at 25 and 50 mg/kg significantly improved cognitive functions, as evidenced by enhanced memory and motor performance in behavioral tests. Subsequent brain tissue analysis revealed that IBC upregulated autophagic proteins to reduce the brain's amyloid beta levels, resulting in decreased expression of neuroinflammation markers.</p><p><strong>Conclusion: </strong>IBC effectively ameliorates AD pathology through autophagy-mediated clearance of Aβ and suppressing neuroinflammation in 5x-FAD mice.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1525364"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical profiles and biological activity of <i>Myrsine africana</i> L.: a comprehensive review.","authors":"Getaneh Worku Moges, Gizachew Mulugeta Manahelohe, Melesse Ababay Assege, Banchamlak Sewachen Tasew, Desilal Kokebie Molla, Aderaw Anteneh Belew","doi":"10.3389/fphar.2025.1565656","DOIUrl":"10.3389/fphar.2025.1565656","url":null,"abstract":"<p><p><i>Myrsine africana</i> L. is a member of the Myrsinaceae family, which encompasses more than 1,000 species and 35 genera predominantly found in tropical and subtropical regions. This plant is abundant in Africa and Asia, and has been traditionally utilized for its aromatic properties in tea, spices, appetizers, carminatives, and flavoring agents. Despite its wide-ranging applications, a comprehensive review of its phytochemical potential and biological effects has not yet been conducted. This study aims to fill that gap by reviewing the phytochemical composition and biological activities of <i>M. africana</i>. Literature was gathered using databases such as Google Scholar, PubMed, Scopus, and Web of Science. The wide range of uses of <i>M. africana</i> can be attributed to its rich phytochemicals, including alkaloids, flavonoids, phenols, terpenoids, and saponins. Among its significant biological activities, <i>M. africana</i> is known for its anti-inflammatory and antioxidant properties. Furthermore, it shows potential in antispasmodic, antityrosinase, antibacterial, anti-aging, and anticancer applications. Additionally, it is used to treat conditions, such as malaria, helminthosis, wounds, tuberculosis, and gastrointestinal complications. Some of the isolated compounds from different parts of <i>M. africana</i> include methylvilangin <b>(11)</b>, methylanhydrovilangin <b>(12)</b>, 2-hydroxychrysophanol <b>(13)</b>, myrsinene <b>(25)</b>, myrsigenin <b>(26)</b>, myrsininone A <b>(27)</b>, myrsininone B <b>(28)</b>, and myrsinoside B <b>(30)</b>, as well as various other flavonoid compounds. This review aims to systematically explore the phytochemical profiles and associated biological activities of <i>M. africana</i>, highlighting key compounds and their pharmacological implications. By bringing together information, it emphasizes the potential of <i>M. africana</i> in drug discovery and future research.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1565656"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-assisted H₂O₂ degradation enhances the bioactivity of Schizophyllan for wound healing and tissue regeneration.","authors":"Hui He, Yu Liu, Qingpeng Li, Fenrou Chen, Lin Zhou","doi":"10.3389/fphar.2025.1562839","DOIUrl":"10.3389/fphar.2025.1562839","url":null,"abstract":"<p><strong>Background: </strong>Schizophyllan (SPG), a bioactive polysaccharide from <i>Schizophyllum commune</i>, possesses significant anti-inflammatory, antioxidant, and immunomodulatory properties. The molecular weight of polysaccharides significantly impacts their structural properties and biological functions. However, the functional characteristics of low molecular weight polysaccharides derived from <i>Schizophyllum commune</i> remain inadequately explored.</p><p><strong>Methods: </strong>This study developed an ultrasound-assisted hydrogen peroxide (H₂O₂) degradation method to produce low-molecular-weight SPG with enhanced bioactivity. The process was optimized using response surface methodology, focusing on ultrasound duration, ultrasonic power, and H₂O₂ concentration. This approach effectively reduced the molecular weight of SPG from 4,409,608 Da to 257,500 Da, yielding three distinct variants: SPG-a (257,500 Da), SPG-b (429,300 Da), and SPG-c (364,800 Da). The bioactivity of these variants was assessed through <i>in vitro</i> cell proliferation and migration assays using BJ and HaCaT cells, as well as an <i>in vivo</i> zebrafish larval caudal fin regeneration model.</p><p><strong>Results: </strong><i>In vitro</i>, SPG-b significantly promoted cell proliferation, increasing BJ and HaCaT cells growth by 53.69% and 14.59%, respectively, at a concentration of 300 μg/mL (<i>p</i> < 0.05), compared to undegraded SPG. Additionally, scratch assays revealed that SPG-a enhanced BJ cells migration by 24.13% (<i>p</i> < 0.05), while SPG-b exhibited most pronounced effect on HaCaT cells migration (17.12%, <i>p</i> < 0.05), compared to the undegraded SPG. <i>In vivo</i>, SPG-c (3.125 mg/mL) significantly improved fin regeneration rates by 6.97% (<i>p</i> < 0.05) in zebrafish larvae, compared to the undegraded SPG.</p><p><strong>Conclusion: </strong>This study demonstrates that ultrasound-assisted H₂O₂ degradation effectively reduces SPG molecular weight while enhancing its functional properties. These findings provide a foundation for the further development of SPG in pharmaceutical and cosmetic applications, highlighting its potential for broader utilization.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1562839"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of atropine in myopia control: insights into choroidal and scleral mechanisms.","authors":"Longxiang Huang, Jingjin Zhang, Youfang Luo","doi":"10.3389/fphar.2025.1509196","DOIUrl":"10.3389/fphar.2025.1509196","url":null,"abstract":"<p><p>In this study, we investigate the inhibitory effects of atropine on the progression of experimental myopia by targeting the functions of the choroid and sclera and exploring its potential therapeutic mechanisms. Form deprivation myopia (FDM) was induced in C57BL/6 mice, with treatment groups receiving atropine. We assessed the effects on ocular morphology, extracellular matrix (ECM) protein expression, choroidal and scleral thickness, and choroidal vascular index (CVI) through histopathology, immunofluorescence, and quantitative quantitative polymerase chain reaction (qPCR). <i>In vitro</i>, mouse scleral fibroblasts (MSFs) were treated with Na₂S₂O₄ to induce hypoxia, followed by atropine treatment. Atropine treatment significantly reduced axial elongation and ECM remodeling in FDM mice, as indicated by a decrease in collagen volume fraction. It restored choroidal and scleral thickness and increased CVI, suggesting improved microcirculation. Atropine also modulated ECM protein expression and reduced the hypoxia marker Hypoxia-Inducible Factor-1α (HIF-1α). <i>In vitro</i>, atropine protected MSFs from hypoxia-induced damage, preserved cytoskeletal integrity, and modulated key signaling pathways, including P53 and β-catenin. These findings suggest that atropine holds promise for controlling myopia progression by improving choroidal microcirculation, reducing scleral hypoxia, and regulating ECM remodeling, supporting its therapeutic application in myopia management.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1509196"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin inhibits pathological retinal neovascularization but promotes retinal fibrosis in experimental neovascular age-related macular degeneration.","authors":"Xin Wang, Xu Liang, Shiya Huang, Mingyan Wei, Yuan Xu, Xiaodong Chen, Yanliang Miao, Rongrong Zong, Xiang Lin, Shiying Li, Zuguo Liu, Qian Chen","doi":"10.3389/fphar.2025.1547492","DOIUrl":"10.3389/fphar.2025.1547492","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the effects and mechanism of action of metformin on retinal neovascularization and fibrosis in a mouse model of neovascular age-related macular degeneration (nAMD).</p><p><strong>Methods: </strong>Very low-density lipoprotein receptor knockout (<i>Vldlr</i> ^-/-) mice, a mouse model of nAMD, were used in this study. <i>Vldlr</i> ^<i>-/-</i> mice were administered metformin on postnatal day (P) 20 for 20 days (early stage of pathological change) or at 5.5 months of age for 45 days (late stage of pathological change). Retinal leakage was examined by fundus fluorescein angiography (FFA). Retinal neovascularization was assessed by lectin staining. Retinal fibrosis was assessed by Western blotting, immunofluorescence staining, and Masson's trichrome staining.</p><p><strong>Results: </strong>Retinal vascular leakage and neovascularization were significantly reduced in <i>Vldlr</i> ^<i>-/-</i> mice treated with metformin compared to those treated with the vehicle at P40. The protein levels of inflammatory factors and phospho(p)-STAT3 were decreased, and P38 and ERK signaling were suppressed in the retinas of metformin-treated <i>Vldlr</i> ^<i>-/-</i> mice relative to those in the control group at P40. Fibrotic markers were upregulated in the retinas of <i>Vldlr</i> ^-/- mice treated with metformin compared to those treated with the vehicle at 7 months. Levels of the inflammatory factors and p-STAT3 were increased, and PI3K/AKT, P38, and ERK signaling were upregulated in the retinas of metformin-treated <i>Vldlr</i> ^<i>-/-</i> mice compared to those in the control group at 7 months.</p><p><strong>Conclusion: </strong>Metformin inhibits pathological retinal neovascularization but promotes fibrosis in experimental nAMD. These results provide evidence and highlight important considerations for the clinical use of metformin in different stages of nAMD.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1547492"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clerodane diterpenoids with anti-inflammatory activity from the tuberous root of <i>Paratinospora sagittata</i> (Oliv.) Wei Wang.","authors":"Hailin Li, Jing Liu, Chuhong Fang, Shanglei Ning","doi":"10.3389/fphar.2025.1561954","DOIUrl":"10.3389/fphar.2025.1561954","url":null,"abstract":"<p><p>Seven novel clerodane diterpenoids, designated tinotanoids I-O (1-7), were isolated from the tuberous roots of <i>Paratinospora sagittata</i> (Oliv.) Wei Wang [syn.: <i>Tinospora sagittata</i> var. yunnanensis (S.Y.Hu) H.S.Lo; Menispermaceae]. The structural elucidation of these new metabolites, including their absolute configurations, was achieved through advanced spectroscopic methods such as mass spectrometry (MS), nuclear magnetic resonance (NMR), electronic circular dichroism (ECD), and X-ray crystallography. Evaluation of their anti-inflammatory activity revealed that metabolites 3 and 4 exhibited potent inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 macrophages, with IC₅₀ values of 12.5 ± 0.5 and 16.4 ± 0.7 <i>μ</i>M, respectively, which are better than those of the positive controls, quercetin and dexamethasone. Additionally, metabolites 3 and 4 effectively inhibited the pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1561954"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Licorice attenuates cisplatin-induced hepatotoxicity by alleviating endoplasmic reticulum stress and apoptosis.","authors":"Jie Li, Xiujuan Yang, Xiaolong Lian, Baojian Li, Quhuan Ma, Lingling Yang, Guangmiao Gao, Yi Deng, Zhijun Yang","doi":"10.3389/fphar.2025.1557125","DOIUrl":"10.3389/fphar.2025.1557125","url":null,"abstract":"<p><p>Cisplatin (CP), a widely used antineoplastic drug, could induce hepatotoxicity and is also one of the most common reasons for drug-induced liver injury (DILI). Licorice (Chinese name GanCao, GC) is a commonly used herbal drug in traditional Chinese medicine (TCM) that has been shown to treat liver diseases and DILI. CP has been documented to induce apoptosis through the promotion of endoplasmic reticulum (ER) stress. However, the exact role of ER stress in the pathogenesis of CP-induced hepatotoxicity remains unclear. A rat DILI model was constructed through intraperitoneal injection of CP, and the anti-DILI effect of GC was detected by liver coefficients, liver function tests, pathological staining, and oxidative stress indices. Additionally, the ER stress and apoptosis indices were investigated by quantitative real-time PCR (qRT-PCR), Western blotting, and immunofluorescence (IF) on CP-induced toxicity in rat liver tissues and LO2 cells. In the model group, liver function indicators significantly elevated, liver lesions more pronounced, and the reactive oxygen species (ROS) level in the liver increased, the expression of ER stress markers, apoptosis factors, and indicators related to the protein kinase RNA-like ER kinase/activating transcription factor 4/C/EBP homologous protein (PERK/ATF4/CHOP) pathway significantly elevated. Treatment of the CP-induced toxicity in the rat model with GC significantly improved liver function, reduced liver lesions, decreased liver ROS. In addition, GC significantly inhibited the expression of ER stress markers, apoptosis factors, and indicators related to PERK/ATF4/CHOP pathway, demonstrating the anti-CP-induced hepatotoxicity effect of GC. In this study, we verified the protective effect of GC in CP-induced hepatotoxicity in rats and clarified its mechanisms related to ER stress and apoptosis.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1557125"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}