Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Febuxostat protects from Doxorubicin induced hepatotoxicity in rats via regulation of NF-κB p65/NLRP3 inflammasome and SIRT-1/AMPK pathways.","authors":"Ahmed M El-Dessouki, Eman H Yousef, Nahed A Raslan, Asmaa I Alwakeel, Samar Ibrahim, Amany A Alzokaky","doi":"10.1007/s00210-025-03808-6","DOIUrl":"https://doi.org/10.1007/s00210-025-03808-6","url":null,"abstract":"<p><p>Doxorubicin (DOX) is a highly potent broad-spectrum anticancer drug, but it has severe side effects, including hepatotoxicity. Therefore, we evaluated the efficacy of febuxostat (FBX), a specific inhibitor of xanthine oxidase and antioxidant, in blocking hepatotoxicity associated with DOX in rats. Rats were treated with FBX (10 or 15 mg/kg/day orally for 2 weeks) and given DOX (15 mg/kg as single dose at the 7th day, intraperitoneal) to induce hepatotoxicity. The results indicated that FBX could reduce the pathological alterations of liver tissues induced by DOX and ameliorate the inappropriate changes in liver function biomarkers (AST, ALT, and ALP) in serum, oxidative stress parameters (catalase, superoxide dismutase, NOX1, NQO-1, HO-1, Keap-1, and Nrf2) and inflammatory markers in the liver (NF-κB p65, TNF-α, NLRP3). Additionally, FBX attenuated the p53, BAX, cytochrome C, caspase-9, and caspase-3 levels to restrain cell apoptosis. In addition, FBX therapy was found to increase protein levels of SIRT-1 and AMPK in the liver. These findings demonstrate that FBX can reduce the hepatotoxicity caused by DOX in rats through mechanisms that counteract oxidative stress, inflammation, and apoptosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414600","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":"Research progress of TRPV4 in pain over the past 20 years: a bibliometric analysis.","authors":"Lele Huang, Qiwen Xuan, Ying Li, Jinghui Huang, Fanfu Fang","doi":"10.1007/s00210-025-03846-0","DOIUrl":"https://doi.org/10.1007/s00210-025-03846-0","url":null,"abstract":"<p><p>This study aims to explore the research hotspots and future research trends of transient receptor potential vanilloid 4 (TRPV4) in pain over the past two decades, with the objective of gaining insight into the development direction and focus of this field. A total of 791 articles were included in this study by searching the Web of Science Core Collection (WOSCC) database. To enhance research quality and accuracy, keywords with similar meanings were combined to eliminate ambiguity. Data visualization analysis was conducted using CiteSpace and VOSviewer, encompassing the examination of countries, research institutions, authors, journals, keywords, references, and categories. Over the past 20 years, 791 scientific articles on TRPV4 and pain have been reviewed, originating from 52 countries, involving 885 research units, 4121 authors, and published in 332 journals. The United States, China, and Japan emerged as core contributors in this field. Prominent research institutions include Duke University (United States) and the University of California, San Francisco (United States). The most prolific researchers include Liedtke, Wolfgang (United States), Bunnett, Nigel W. (United States), and Yue, Shou-wei (China). Research on TRPV4 and pain predominantly focuses on the molecular mechanisms, role of pain models, drug development, and clinical applications, aimed at advancing pain treatment. This study provides a comprehensive overview of the literature on TRPV4 and pain over the past two decades, offering researchers and scholars fresh insights into the field's development trends and future directions.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414602","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":"Efforts of the Pharmaceuticals and Medical Devices Agency of Japanese regulatory agency in supporting biosimilar development and disseminate information.","authors":"Ryosuke Kuribayashi, Aya Hariu, Yuka Saino, Kayo Shinohara","doi":"10.1007/s00210-025-03874-w","DOIUrl":"https://doi.org/10.1007/s00210-025-03874-w","url":null,"abstract":"<p><p>Information on biosimilars was rarely disseminated on the Pharmaceuticals and Medical Devices Agency (PMDA) website of the Japanese Regulatory Agency until the fiscal year (FY) 2022. Therefore, the PMDA website for biosimilars was created in FY 2023. This study confirmed the PMDA website for biosimilars and surveyed information about the approval fiscal year, brand name, indications at the initial approval, type of biopharmaceuticals, and disease area at the initial approval based on review reports and the \"List of Approved Products.\" The PMDA website for biosimilars provides information on the definition of biosimilar, approved biosimilar products, related guidelines and notifications, learning videos, presentation material, and publication articles. As of March 2024, 35 biosimilars were approved in Japan based on the following 18 active pharmaceutical ingredients: somatropin, epoetin-alfa, filgrastim, infliximab, insulin glargine, rituximab, etanercept, trastuzumab, agalsidase beta, bevacizumab, teriparatide, darbepoetin-alfa, insulin lispro, adalimumab, insulin aspart, ranibizumab, pegfilgrastim, and ustekinumab. The disease area comprised nine patterns: rheumatology, oncology, hematology, gastroenterology, dermatology, endocrinology, ophthalmology, bone, and inborn errors represented in numbers and percentages for each pattern: 12 (23.1%), 9 (17.3%), 8 (15.4%), 7 (13.5%), 7 (13.5%), 5 (9.6%), 2 (3.8%), 1 (1.9%), and 1 (1.9%), respectively. This website provides various information regarding biosimilars in Japan. It will be more important to effort the understanding and education for the healthcare providers and patients on biosimilar regulations. Moreover, information should be disseminated through the PMDA website of biosimilars to accelerate and ensure transparency regarding regulatory approvals and biosimilar regulations.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414543","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":"How strong the interaction really are? Application of nanoITC in the analysis of the interaction between newly synthesized substances with potential anticancer activity and model carrier proteins.","authors":"Aleksandra Owczarzy, Wojciech Rogóż, Karolina Kulig, Andrzej Zięba, Małgorzata Maciążek-Jurczyk","doi":"10.1007/s00210-025-03884-8","DOIUrl":"https://doi.org/10.1007/s00210-025-03884-8","url":null,"abstract":"<p><p>The aim of this work was to extend the existing knowledge of the interaction between newly synthetized substances with anticancer properties (5-methyl-12(H)-chino[3,4-b]-[1,4]-benzothiazine chloride (Salt1), 9-fluoro-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride (Salt2), and 9-amino-5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazine chloride (Salt3) with model plasma carrier proteins. The thermodynamic profile of ligand-protein complexation and the contribution of bonds responsible for complex formation have been studied using calorimetry technique. The research has theoretical and experimental nature, but from a scientific point of view is novelty due to promising biological properties of Salt1, Salt2, and Salt3 and provide an important basis for further in vitro and in vivo studies. All measurements were conducted using nanoITC calorimeter (TA Instruments, New Castle, USA). The results were analyzed using Launch NanoAnalyze program (TA Instruments, New Castle, USA). Based on the obtained data, it is safe to consider the bonds within Salt1-HSA, Salt3-HSA, Salt1-AGP, Salt3-AGP, and Salt3-HGG complexes to be predominantly hydrophobic (ΔH > 0 and ΔS > 0) with K_a values: (1.95 ± 0.59)·10⁶, (34.6 ± 0.06)·10⁶, (3.34 ± 0.35)·10⁶, (0.45 ± 0.14)·10⁶, and (0.56 ± 0.09)·10⁶ (L·mol^-1), respectively. In contrast, complexes of Salt2 with proteins were stabilized by hydrogen bonds and/or van der Waals interaction (ΔH < 0 and ΔS < 0) and K_a values (25.50 ± 9.20)·10⁶, (1.37 ± 0.37)·10⁶, and (1.17 ± 0.01)·10⁶ (L·mol^-1) for HSA, AGP, and HGG, respectively, have been obtained. In turn, the reaction of Salt1-HGG complex formation was accompanied by ionic bonds (ΔH ≅ 0, ΔS > 0, and K_a = (0.64 ± 0.45)·10⁶ (L·mol^-1)). Regardless of the involvement of bonds and interaction between the ligands and proteins, the reactions occurred spontaneously (ΔG < 0). By comparing the binding parameters obtained using nanocalorimetric measurements and previously obtained spectroscopic data, due to the characteristic of complex formation, Salt2 was selected for further analysis. In addition, it was found that, despite the many advantages of the nanoITC technique, it still requires coupling with other techniques that allow analysis of the complexes formed at the molecular level and complementing spectroscopic analysis. Therefore, the use of these two techniques should be considered simultaneously.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409060","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":"Effect of NADPH oxidase inhibitor apocynin on human lung cancer A549 cells via Bcl-2, Bax, caspase-3, and NF-κB signaling pathway.","authors":"Betul Apaydın Yıldırım, Tuba Dogan, İsmail Bolat, Ali Can Ozcan, Rabia Kocak","doi":"10.1007/s00210-025-03833-5","DOIUrl":"https://doi.org/10.1007/s00210-025-03833-5","url":null,"abstract":"<p><p>Apocynin (AP) is an anti-inflammatory drug with different therapeutic effects. This study aimed to investigate the antiproliferative, apoptotic, and antioxidant effects of AP on human lung adenocarcinoma cells (A549) and to investigate the effects on Bax, Bcl-2, NF-κB, and caspase-3 signaling pathways that may play a role in the pathogenesis of lung cancer. Cell viability was measured by MTT and cell apoptosis, and detection of cell death was measured by ELISA. IMA, AOPP, MDA, and GSH levels, SOD and CAT activities, and Bcl-2, Bax, NF-κB, and caspase-3 expression levels were analyzed from the obtained cell lysates. As a result, according to the findings obtained, IMA and MDA levels decreased in the A549 cancer cell line, while GSH levels and SOD and CAT activity increased. It was determined that the application of apocynin to A549 cells significantly reduced cell viability and directed the cells to apoptosis, increased Bax, NF-κB, and caspase-3 expression, and decreased Bcl-2 expressions. Since all of the data obtained were not found in the literature about the use of apocynin in the A549, the study conducted is pioneering. Our study demonstrates the potential of apocynin for cancer therapy possibly targeting the apoptotic pathway.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409054","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":"Combining network pharmacology and RNA sequencing to reveal the mechanism of emodin for the treatment of human neuroblastoma.","authors":"Hai-Mei Jiang, Shang-Yi Huang, Dan Huang, Yan Zhao, Yi Yuan, Hai-Fu Huang, Ying Tang, Jin-Fang Zhang","doi":"10.1007/s00210-025-03865-x","DOIUrl":"https://doi.org/10.1007/s00210-025-03865-x","url":null,"abstract":"<p><p>Neuroblastoma (NB), as a highly metastatic tumor, represents the most common pediatric extracranial malignancy. Emodin is a natural product extracted from several traditional Chinese medicines, exerting potent anti-cancer properties in various cancer types. However, the detailed mechanism of emodin in the treatment of NB remains unclear. Network pharmacology was employed to explore the mechanism of emodin for the treatment of NB. The cell proliferation markers, cell cycle, cell cycle-related genes, and DNA damage-relevant genes of SH-SY5Y cell were examined by a battery of assays. Animal xenografts were used to evaluate tumor inhibition effect of emodin and perform RNA sequencing. Binding affinity of emodin and essential signaling proteins was investigated using molecular docking and confirmed by western blot analysis. The expression of epithelial-mesenchymal transition markers was also examined by western blot. Network pharmacology uncovered that emodin regulated cell cycle, p53 pathway, and PI3K/AKT pathway in NB. Emodin suppressed the cell proliferation in vitro by inducing the S phase arrest in SH-SY5Y cells, and the animal xenografts confirmed the anti-cancer activity of emodin in vivo. Further RNA-sequencing investigation showed that PI3K/AKT signaling is a potential pathway with emodin treatment. Our results validated that this signaling was indeed suppressed in the emodin-mediated anti-NB process, and molecular docking demonstrated that emodin bound strongly to PI3K and AKT1. And, emodin inhibited the metastasis of SH-SY5Y cells in vitro. Emodin restrained tumor growth by inducing S phase arrest and inhibited metastasis through inhibiting the PI3K/AKT signaling in SH-SY5Y cells.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409053","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":"Inhibitory effects of cornuside on human liver cytochrome P450 enzymes.","authors":"Yanmo Yang, Ke Zhang, Mi Zhou","doi":"10.1007/s00210-025-03856-y","DOIUrl":"https://doi.org/10.1007/s00210-025-03856-y","url":null,"abstract":"<p><p>Cornuside is an iridoid glycoside isolated from the fruits of Cornus officinalis Sieb. et Zucc. with antiallergic and hypoglycemic properties. This study aimed to investigate the interaction of cornuside with cytochrome P450 (CYP) enzymes which may provide a reference for the clinical application of Cornus officinalis. The impact of cornuside on CYP enzyme activity in human liver microsomes (HLMs) was examined in the presence of 0, 2.5, 5, 10, 25, 50, and 100 µM of cornuside. In order to estimate the inhibition properties, Lineweaver-Burk plots were plotted and kinetic parameters were obtained. Furthermore, the time-dependent inhibition of CYP3A4 activity by cornuside was also assessed. The activity of CYP3A4, 2C19, and 2E1 was suppressed by cornuside, with half-maximal inhibitory concentration (IC₅₀) values of 13.80, 19.44, and 24.55 µM, respectively. Furthermore, the inhibitory effect of cornuside was found to be non-competitive (K_i = 7.13 µM) and time-dependent (K_I = 7.19 µM, K_inact = 0.042 min^-1), whereas the inhibitory effect on CYP2C19 and 2E1 was found to be competitive, with K_i values of 9.92 µM and 12.38 µM, respectively. In vitro studies revealed that cornuside inhibited CYP3A4, 2C19, and 2E1. This indicates the possibility of drug-drug interaction between cornuside and drugs that are metabolized by these CYP enzymes when co-administered. These findings may provide a theoretical basis for clinical prescribing, particularly in the context of co-administration.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409018","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":"The neurotoxic effects of lead acetate and the abrogating actions of 6-gingerol-rich extract of ginger via modulation of antioxidant defence system, pro-inflammatory markers, and apoptotic cascade.","authors":"Maryam Tayo Ayinla, Abraham Olufemi Asuku","doi":"10.1007/s00210-025-03873-x","DOIUrl":"https://doi.org/10.1007/s00210-025-03873-x","url":null,"abstract":"<p><p>Lead exposure is a public health concern and it has been linked to cognitive deficit, memory impairment, and neurotoxicity. This study was designed to investigate the effect of 6-gingerol-rich extract of ginger (6-GREG) on oxidative stress, inflammation, and apoptosis in lead acetate (PbAc)-induced neurotoxicity in male Wistar rats. Twenty-five (25) male Wistar rats in total were divided into five groups at random (n = 5). The control group received 0.5 ml of normal saline, the PbAc-treated group received 7.5 mg/kg of PbAc, the vitamin C, 6-GREG (100), and 6-GREG (200) groups received 7.5 mg/kg of PbAc followed by administration of vitamin C (100 mg/kg), 6-GREG (100 mg/kg), and 6-GREG (200 mg/kg) respectively for 2 weeks. Following behavioral tests, the rats were euthanized, and their brain tissues were homogenized for biochemical analysis. When compared to the control group, the administration of PbAc caused behavioral alterations as well as a significant (p < 0.05) decrease in the activities of catalase, glutathione peroxidase, as well as reduced glutathione and Bcl-2 levels in the PbAc-treated group. Furthermore, the PbAc-treated group showed a statistically significant rise (p < 0.05) in brain acetylcholinesterase, malondialdehyde, nitric oxide, interleukin-1-beta, tumor necrosis factor-α, and caspase-9 levels in comparison to the control. Administration of both 100 mg/kg and 200 mg/kg of 6-GREG effectively reversed these behavioral and biochemical changes in 6-GREG (100)- and 6-GREG (200)-treated groups respectively compared to the PbAc-treated group. Consequently, the study reveals the role of 6-GREG in attenuating PbAc-induced neurotoxicity and brain damage via antioxidative, anti-inflammatory, and anti-apoptotic mechanisms.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399511","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":"Bovine serum albumin nanoparticles encapsulating Dasatinib and Celecoxib for oral cancer: Preparation, characterization, and in-vitro evaluation.","authors":"Ghadeer AbouBakr Aly, Sally A Sabra, Medhat Haroun, Maged W Helmy, Nermine Moussa","doi":"10.1007/s00210-025-03829-1","DOIUrl":"https://doi.org/10.1007/s00210-025-03829-1","url":null,"abstract":"<p><p>Oral squamous cell carcinoma is a diverse complex disease. Despite the ever-expanding repertoire of anti-cancer treatments, the outcomes are often inadequate highlighting the urgent need for innovative approaches. In this regard, co-targeting signaling pathways such as Src and COX-2 have attracted growing attention in several cancers, but co-inhibition of these two pathways using dasatinib and celecoxib has not been explored in oral cancer. However, the therapeutic efficacy of these drugs is limited due to their low aqueous solubility. Nanoencapsulation can improve this by utilizing naturally available proteins due to their ease of fabrication and biocompatibility. In this sense, this study aimed at preparing and characterizing dastatinib (DAS)/celecoxib (CXB)-loaded bovine serum albumin (BSA) nanoparticles as well as investigating their potential anticancer effects in vitro on SCC-4 oral cancer cell line. DAS/CXB-loaded BSA nanoparticles (NPs) were fabricated by the desolvation method, then characterized in terms of their hydrodynamic particle size, zeta potential, morphology and in vitro drug release. The IC50 was determined via the MTT assay. Cyclin D1, COX-2, p-Src and FAK protein expression levels were determined using ELISA while active caspase-3 was determined colorimetrically. DAS/CXB-loaded BSA NPs exhibited particle size of 336.6 ± 1.098 nm with low PDI value of 0.211 ± 0.019 and zeta potential of -35.0 ± 4.03 mV. Moreover, the in vitro cytotoxicity study revealed decreased IC50 value in case of the dual drug-loaded NPs compared to all treated groups, with significant decrease in the expression levels of cyclin D1, COX-2, p-Src and FAK proteins, besides, increased caspase-3 level. The findings suggest that DAS/CXB-loaded BSA NPs could serve as a drug delivery platform with increased antitumor effectiveness.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399498","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":"Signaling pathways behind the biological effects of tanshinone IIA for the prevention of cancer and cardiovascular diseases.","authors":"Homa Shahrokhi, Javad Asili, Zahra Tayarani-Najaran, Motahareh Boozari","doi":"10.1007/s00210-025-03857-x","DOIUrl":"https://doi.org/10.1007/s00210-025-03857-x","url":null,"abstract":"<p><p>Tanshinone IIA (Tan IIA) is a well-known fat-soluble diterpenoid found in Salvia miltiorrhiza, recognized for its various biological effects. The molecular signaling pathways of Tan IIA have been investigated in different diseases, including the anti-inflammatory, hepatoprotective, renoprotective, neuroprotective effects, and fibrosis prevention. This article provides a brief overview of the signaling pathways related to anti-cancer and cardioprotective effects of Tan IIA. It shows that Tan IIAs anti-cancer ability has good expectation through multiplicity mechanisms affecting various aspects' tumor biology. The major pathways involved in its anti-cancer effects include inhibition of PI3/Akt, MAPK, and p53/p21 signaling which leads to enhancement of immune responses and increased radiation sensitivity. Some essential pathways responsible for cardioprotective effects induced by Tan IIA are PI3/AKT activation, MAPK, and SIRT1 promoting protection against ischemia/reperfusion injury in myocardial cells as well as inhibiting pathological remodeling processes. Finally, the article underscores the complex and specific signaling pathways influenced by Tan IIA. The PI3/Akt and MAPK pathways play critical roles in the anti-cancer and cardioprotective effects of Tan IIA. Particularly, Tan IIA suppresses the proliferation of malignancies in cancerous cells but stimulates protective mechanisms in normal cardiovascular cells. These findings highlight the importance of investigating molecular signaling pathways in evaluating the therapeutic potential of natural products. Studying about signaling pathways is vital in understanding the therapeutic aspects of Tan IIA and its derivatives as anti-cancer and cardio-protective agents. Further research is necessary to understand these complex mechanisms.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399504","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}