Journal of Pharmacy and Pharmacology最新文献

{"title":"PD15, a steroidal saponin, induces apoptosis of HCT116 colorectal cancer cells via suppressing the Akt/GSK3β pathway.","authors":"Minna Yao, Yi Ding, Yang Sun, Kai Gao, Ruili Li, Wei Zhang, Weiwei Li, Yanhua Wang, Yi Qiao, Haifeng Tang, Jingwen Wang","doi":"10.1093/jpp/rgae151","DOIUrl":"10.1093/jpp/rgae151","url":null,"abstract":"<p><strong>Objectives: </strong>PD15, a novel natural steroidal saponin extracted from the rhizomes of Paris delavayi Franchet, has demonstrated a strong cytotoxic effect against HepG2 and U87MG cells. However, its therapeutic effects on colorectal cancer (CRC) and the underlying molecular mechanisms remain unclear.</p><p><strong>Methods: </strong>MTT assay, clonogenic assay, Hoechst 33258 staining, flow cytometry, molecular docking, and western blot were used to investigate the mechanism of PD15 in HCT116 cell lines. Additionally, the anti-CRC effects of PD15 were evaluated in vivo using HCT116 xenograft models.</p><p><strong>Key findings: </strong>PD15 significantly inhibited cell proliferation and induced G0/G1 phase arrest in HCT116 cells. Furthermore, PD15 upregulated cleaved Caspase 3 and 9, cleaved PARP, and Bax expression levels while downregulating Bcl-2, leading to apoptosis. Further experiments revealed that PD15 downregulated the protein expression of p-Akt and p-GSK3β, with LY294002 (a PI3K/Akt inhibitor) enhancing PD15-induced apoptosis and its effects on Akt/GSK3β-associated proteins. In addition, molecular docking demonstrated that PD15 exhibited strong binding affinity with Akt and GSK3β. Critically, PD15 inhibited CRC growth in vivo without causing apparent toxicity in mice.</p><p><strong>Conclusions: </strong>These findings indicate that PD15 could trigger apoptosis by suppressing the Akt/GSK3β signaling pathway in HCT116 cells.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"834-844"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066294","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":"Dihydroisotanshinone I regulates ferroptosis via PI3K/AKT pathway to enhance cisplatin sensitivity in lung adenocarcinoma.","authors":"Feng-Jiao Li, Li-Chen Gao, Hui-Zhi Long, Zi-Wei Zhou, Hong-Yu Luo, Shuo-Guo Xu, Shang-Ming Dai, Jin-Da Hu","doi":"10.1093/jpp/rgae085","DOIUrl":"10.1093/jpp/rgae085","url":null,"abstract":"<p><strong>Objectives: </strong>Dihydroisotanshinone I (DT) is a kind of diterpenoid compound extracted from the dried roots of Salvia miltiorrhiza Bunge, and exhibits multiple biological activities including anti-tumor activity. Cisplatin is one of the first-line drugs for the treatment of lung adenocarcinoma (LAUD), but the drug resistance and toxicity limit its efficacy. DT is known to induce apoptosis and ferroptosis, but it is unclear whether DT can inhibit the cisplatin-resistant LAUD cells and reverse the drug resistance in LAUD. Therefore, our study intends to establish the cisplatin-resistant human LAUD cells (A549/DDP), and figure out the influence and related mechanisms of DT reversing cisplatin resistance in A549/DDP cells, so as to provide a theoretical basis for the DT as a new natural candidate for the treatment of LAUD.</p><p><strong>Methods: </strong>The establishment of A549/DDP was the continuous stimulation by exposing A549 to gradient concentrations of Cisplatin. The cell viability of A549 and A549/DDP was detected by CCK-8 kit, and the IC50 value was calculated. The morphological changes of A549 and A549/DDP cells were observed by an inverted microscope. The contents of malondialdehyde (MDA) and glutathione (GSH) in A549/DDP cells after drug treatment were detected by related kits. The levels of Fe2+, cytosolic reactive oxygen species (ROS), and lipid reactive oxygen species (lipid ROS) were detected by a fluorescence microplate reader or fluorescence cell imager according to the related fluorescent probe kit instructions. Western blot was used to detect the expressions of PI3K, phospho-PI3K, AKT, phospho-AKT, MDM2, p53, GPX4, and SLC7A11 in A549/DDP after different drug treatments.</p><p><strong>Key findings: </strong>Our study demonstrated that the inhibitory effect of DT on A549 and A549/DDP cells was time-dependent and concentration-dependent, and DT and DDP had a synergistic effect on inhibiting the proliferation of A549/DDP cells. Furthermore, DT mainly induced ferroptosis in A549/DDP cells and synergized with cisplatin to promote ferroptosis in A549/DDP cells. The result of KEGG pathway analysis, molecular docking and western blot showed that DT could enhance the cisplatin sensitivity of A549/DDP by inhibiting PI3K/MDM2/P53 signaling pathway.</p><p><strong>Conclusions: </strong>Consequently, we concluded that DT promotes ferroptosis in cisplatin-resistant LAUD A549/DDP cells. Additionally, DT reverses cisplatin resistance by promoting ferroptosis via PI3K/MDM2/P53 pathway in A549/DDP cells.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"752-767"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751973","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 therapeutic potential of curculigoside in poststroke depression: a focus on hippocampal neurogenesis and mitochondrial function.","authors":"Ning-Xi Zeng, Xin Chen, Xiao-Yan Yang, De-Sheng Chen, Mei Shen","doi":"10.1093/jpp/rgae091","DOIUrl":"10.1093/jpp/rgae091","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effects and mechanism of curculigoside against poststroke depression (PSD).</p><p><strong>Methods: </strong>In vivo, a PSD rat model was created by combining bilateral common carotid artery occlusion and chronic unpredictable mild stress stimulations. After 4-week modeling and intragastrically administration of curculigoside, the effects of curculigoside on behavior, hippocampal neurogenesis, and hippocampal mitochondrial oxidative phosphorylation (OxPhos) were investigated. In vitro, PSD-like primary neural stem cells (NSCs) model was established by oxygen-glucose deprivation/recovery (OGD/R) combing high-corticosterone (CORT) concentration, followed by treatment with curculigoside. The investigation subsequently examined the impact of curculigoside on mitochondrial OxPhos, proliferation, and differentiation of NSCs under OGD/R + CORT conditions.</p><p><strong>Key findings: </strong>In vivo, PSD rats showed significantly depressive behaviors, dysfunctional neurogenesis in hippocampus, as well as decreased hippocampus adenosine triphosphate (ATP) levels, reduced electron transport chain complexes activity, and downregulates mitochondrial transcription factor A (TFAM) and PPAR-gamma coactivator 1 alpha (PGC-1α) expression in hippocampus. In vitro, OGD/R +CORT significantly injured the proliferation and differentiation, as well as impaired the mitochondrial OxPhos in NSCs. Curculigoside treatment was effective in improving these abnormal changes.</p><p><strong>Conclusion: </strong>Curculigoside may repair hippocampal neurogenesis in PSD rats by enhancing hippocampal mitochondrial OxPhos, and has shown a great potential for anti-PSD.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"768-782"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620262","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":"Modulation of PPAR-γ/Nrf2 and AGE/RAGE signaling contributes to the chrysin cardioprotection against myocardial damage following ischemia/reperfusion in diabetic rats.","authors":"Neha Rani, Dharamvir Singh Arya","doi":"10.1093/jpp/rgae140","DOIUrl":"10.1093/jpp/rgae140","url":null,"abstract":"<p><strong>Objective: </strong>Advanced glycation end products/receptor for AGEs (AGE/RAGE) signaling has a well-established role in the etiology of diabetic-related cardiovascular disorders. The purpose of the study was to elucidate the role of chrysin, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, against ischemia/reperfusion (IR) injury in diabetic rats and its functional interaction with the AGE/RAGE signaling pathway.</p><p><strong>Methods: </strong>A single intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) was administered to rats for induction of diabetes. Rats having blood glucose levels more than 300 mg/dl following a 72 hr STZ injection were classified as diabetic. PPAR-γ antagonist GW9662 (1 mg/kg, i.p.), chrysin (60 mg/kg, p.o.), or both were administered to diabetic rats for 4 weeks. On the 29th day, rats were given ischemia for 45 min and then reperfusion for 1 hr to induce myocardial infarction (MI).</p><p><strong>Key findings: </strong>Pretreatment with chrysin significantly improved hemodynamic status, ventricular functions, and cardiac injury markers in diabetic myocardium. Increased PPAR-γ/Nrf2 and decreased RAGE protein expressions were linked to this improvement. Chrysin pretreatment resulted in the upregulation of endogenous antioxidants and reduced TBARS levels. Moreover, chrysin significantly decreased inflammation and apoptosis in diabetic myocardium.</p><p><strong>Conclusion: </strong>PPAR-γ/Nrf2 co-activation by chrysin ameliorated IR-induced MI in diabetic rats, possibly via modulating AGE/RAGE signaling.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"794-804"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823497","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 state and trends of cinnamaldehyde research over the past three decades: a bibliometric and visualized analysis.","authors":"Huize Zhang, Longfei Si, Chenhao Liu, Yi Liu","doi":"10.1093/jpp/rgaf019","DOIUrl":"10.1093/jpp/rgaf019","url":null,"abstract":"<p><strong>Objectives: </strong>As an aromatic aldehyde, Cinnamaldehyde (CAL) is the representative bioactive component of cinnamon, possessing extensive applications in the fields of pharmaceuticals, chemicals, food, and feed. The objective of the present study is to elucidate the state and trends of CAL research via bibliometric and visualized analysis.</p><p><strong>Methods: </strong>Research on CAL was obtained from the Web of Science Core Collection, and knowledge graphs were created employing CiteSpace software. Bibliometric analysis was conducted on 6205 articles published from 1994 to 2023.</p><p><strong>Key findings: </strong>The findings indicate a steadily growing trend in the quantity of papers published on CAL. The collaborative network visualization analysis has determined that China, the Chinese Academy of Sciences, and Kumar Venkitanarayanan have the highest number of publications among all countries, institutions, and authors, respectively. According to the keyword and cocited reference analysis, the primary research hotspots and frontiers include pharmacological effect, underlying mechanism, chemical structure modification, encapsulation technology, and delivery system, highlighting the cross-disciplinary characteristic of CAL research.</p><p><strong>Conclusions: </strong>This study delineates the research hotspots and trends of CAL. Future research should focus on exploring the pharmacological effects and mechanisms of CAL in more depth, optimizing chemical derivatization methods, and refining stimuli-responsive smart release systems of CAL.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"729-751"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016315","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":"Rhein induces apoptosis of AGS and MGC803 cells by regulating the Ras/PI3K/AKT and p38/MAPK signaling pathway.","authors":"Meiqi Wan, Anna Gan, Jun Dai, Fei Lin, Ruixuan Wang, Bo Wu, Tingxu Yan, Ying Jia","doi":"10.1093/jpp/rgae115","DOIUrl":"10.1093/jpp/rgae115","url":null,"abstract":"<p><strong>Objectives: </strong>Rhein is one of the main bioactive compounds in the Polygonaceae plant, and has been proven to have anti-cancer activity in some reports. But the mechanism of Rhein in the treatment of gastric cancer (GC) is limited reported. In this research, network pharmacology combined with in vitro experiments was used for systematically studying the mechanism of Rhein.</p><p><strong>Methods: </strong>Network pharmacology confirmed the major effect signaling pathway and key targets of Rhein in the treatment of GC. Cell viability assay, colony formation assay, fluorescence probe assay, apoptosis assay, western blot and qRT-PCR verified the mechanism of Rhein in the treatment of GC cells (AGS and MGC803 cells).</p><p><strong>Key findings: </strong>The results showed that Rhein significantly induced the apoptosis process of AGS and MGC803 cells by regulating the Ras/phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and the p38/mitogen-activated protein kinase signaling pathways. The AKT activator (SC79) and p38 inhibitor (SB202190) inhibited Rhein-induced apoptosis.</p><p><strong>Conclusions: </strong>All results proved that Rhein could be recognized as a potential natural drug for the treatment of GC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"783-793"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406534","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":"Repurposing the familiar: Future treatment options against chronic kidney disease.","authors":"Rohan Bhadange, Anil Bhanudas Gaikwad","doi":"10.1093/jpp/rgaf002","DOIUrl":"10.1093/jpp/rgaf002","url":null,"abstract":"<p><strong>Objectives: </strong>Chronic kidney disease (CKD) is a serious health issue with rising morbidity and mortality rates. Despite advances in understanding its pathophysiology, effective therapeutic options are limited, necessitating innovative treatment approaches. Also, current frontline treatments that are available against CKD are not uniformly effective and often come with significant side effects. Therefore, identifying new therapeutic targets or improving existing treatments for CKD is crucial. Drug repurposing is a promising strategy in the drug discovery process that involves screening existing approved drugs for new therapeutic applications.</p><p><strong>Key findings: </strong>This review discusses the pharmacological mechanisms and clinical evidence that support the efficacy of these repurposed drugs. Various drugs classes such as inodilators, endothelin-1 type A (ET-1A) receptor antagonists, bisphosphonates, mineralocorticoid receptor (MR) antagonists, DNA demethylating agents, nuclear factor erythroid 2-related factor 2 (NRF2) activators, P2X7 inhibitors, autophagy modulators, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI) are discussed that could remarkably contribute against CKD.</p><p><strong>Summary: </strong>The review critically examines the potential for repurposing well-established drugs to slow the progression of CKD and enhance patient outcomes. This review emphasizes the importance of a multidisciplinary approach in advancing the field of drug repurposing, ultimately paving the way for innovative and effective therapies for patients suffering from CKD.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"715-728"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007254","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":"Targeting together cholinesterases and serotonin reuptake against Alzheimer's disease.","authors":"Thomas Guiselin, Cédric Lecoutey, Christophe Rochais, Patrick Dallemagne","doi":"10.1093/jpp/rgaf041","DOIUrl":"https://doi.org/10.1093/jpp/rgaf041","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss, with limited therapeutic options. Traditional treatments primarily focus on acetylcholinesterase inhibitors (AChEIs), which aim to increase acetylcholine levels in the brain, and selective serotonin reuptake inhibitors (SSRIs), which modulate serotonin levels. However, these treatments often provide only modest symptom relief. This review explores the potential benefits of combined targeting of cholinesterases and serotonin reuptake as a novel therapeutic strategy for AD. We discuss the pathophysiological role of acetylcholine and serotonin in AD, highlighting their impact on cognitive function, mood regulation, and neuroplasticity. By targeting both cholinergic and serotonergic systems, this dual approach may offer synergistic effects, improving cognitive function, reducing neuropsychiatric symptoms, and enhancing neuroprotective mechanisms. The review also examines preclinical and clinical studies investigating the efficacy of combination therapies and outlines the challenges and opportunities in their development. Ultimately, this combined targeting approach holds promise for providing more effective and comprehensive treatment options for AD, addressing both cognitive and behavioural symptoms associated with the disease.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248468","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":"Correction to: Isoliquiritigenin attenuates inflammation and modulates Nrf2/caspase-3 signalling in STZ-induced aortic injury.","authors":"","doi":"10.1093/jpp/rgaf046","DOIUrl":"https://doi.org/10.1093/jpp/rgaf046","url":null,"abstract":"","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234429","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":"Thymol suppressed tumor growth in vitro and in vivo through inducing calcium overload in colorectal cancer.","authors":"Hao Lin, Zongjun Chen, Weizhong Yang, Xianwei Wang","doi":"10.1093/jpp/rgaf040","DOIUrl":"https://doi.org/10.1093/jpp/rgaf040","url":null,"abstract":"<p><strong>Background: </strong>Thymol, a bioactive phenolic compound, has proven to possess multiple anti-cancer activities, yet the function and underlying mechanism in colorectal cancer (CRC) remain unclear.</p><p><strong>Objectives: </strong>To shed light on the possible therapeutic effects of thymol in CRC based on calcium homeostasis regulation, and seek to explore the molecular pathways of calcium overload in the thymol-induced anti-CRC activity.</p><p><strong>Methods: </strong>The effects of thymol on cell proliferation, viability, apoptosis, anti-inflammatory effects, and calcium overload phenotype were investigated in HCT116 and CT26 cells. In addition, the in vivo therapeutic efficacies of thymol on CT26 xenograft tumor were also researched. Furthermore, molecular mechanisms of thymol-induced calcium overload were detected by Western blot, RT-qPCR, and immunofluorescence assays.</p><p><strong>Results: </strong>We demonstrated that thymol significantly inhibited the proliferation, viability, and induced apoptosis of HCT116 and CT26 cells. And, thymol suppressed the secretion of inflammatory factors. Furthermore, thymol promoted cell damage mediated by increased mitochondrial membrane potential in both two cells. In addition, thymol triggered the energy metabolism inhibition induced by calcium overload in HCT116 and CT26 cells. Besides, in vivo experiments based on CT26 xenograft tumor model also validated the positive anti-CRC activities.</p><p><strong>Conclusions: </strong>Thymol inhibits CRC partially through inducing calcium overload, which provides an innovative solution for developing anti-CRC drugs.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248469","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}