{"title":"Mechanism of traditional drug treatment of cancer-related ascites: through the regulation of IL-6/JAK-STAT3 pathway.","authors":"Yehan Sun, Pengcheng Zhang, Jia Ma, Youmou Chen, Xingxing Huo, Hang Song, Yongfu Zhu","doi":"10.1093/jpp/rgae111","DOIUrl":"10.1093/jpp/rgae111","url":null,"abstract":"<p><strong>Context: </strong>Our clinical observation found that JiJiaoLiHuang Pill (JJLH), a classic traditional Chinese medicine (TCM) formulation, can significantly reduce the abdominal circumference of patients with malignant ascites, increase urine output, and improve the quality of life of patients, with preliminary efficacy. But, the exact mechanism is not yet clear.</p><p><strong>Objective: </strong>Based on the above observations, the potential mechanism of action of the treatment was preliminarily explored.</p><p><strong>Methods: </strong>We identified active ingredients by constructing a \"Chinese medicine ingredient-key target-target\" network, and verified them by molecular docking using AutoDock tools and PyMOL. Finally, we conducted preliminary verification of the validated pathways and targets using a mouse model of liver cancer ascites.</p><p><strong>Results: </strong>Network pharmacology analysis obtained the top five active ingredients were quercetin, EUPATIN, kaempferol, Obtucarbamate B, and isorhamnetin and the top five key genes were SRC, HSP90AA1, MAPK1, STAT3, and PIK3CA. Molecular docking showed that all 5 active compounds were closely bound to key target genes (binding energy <-6). The animal experiment results showed that JJLH can significantly reduce abdominal circumference, increase urine output, and exhibit dose-dependent inhibition of the AQP-3/JAK-STAT-3 signaling pathway and the expression of related inflammatory factors.</p><p><strong>Conclusions: </strong>The JJLH potentially inhibits the recurrence of liver cancer malignant ascites through the AQP-3/JAK-STAT-3 pathway and affects the prognosis of MA patients.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"264-274"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622678","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}
Jianing Li, Jialiang Chen, Dan Qu, Lin Zhu, Shuhong Ye, Ming Li, Wei Li, Yan Ding
{"title":"Systems pharmacology-based drug discovery from Amaryllidaceae alkaloids and investigation of mechanisms of action in treatment of Alzheimer's disease.","authors":"Jianing Li, Jialiang Chen, Dan Qu, Lin Zhu, Shuhong Ye, Ming Li, Wei Li, Yan Ding","doi":"10.1093/jpp/rgae113","DOIUrl":"10.1093/jpp/rgae113","url":null,"abstract":"<p><strong>Objectives: </strong>Given the success of galanthamine in treating Alzheimer's disease, this study aims to establish an effective method to find drugs from Amaryllidaceae alkaloids and to clarify its mechanism in treating Alzheimer's disease.</p><p><strong>Methods: </strong>The pharmacodynamic basis and mechanism of action between Amaryllidaceae alkaloids and Alzheimer's disease were explored by constructing a compound-target-disease network, targets protein-protein interaction, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and molecular docking verification.</p><p><strong>Key findings: </strong>In total, a chemical library of 357 potential alkaloids was constructed. A total of 100 active alkaloid components were identified. Thirty-nine associated targets were yielded based on network construction, and the key targets were defined as HSP90AA1, ESR1, NOS3, PTGS2, and PPARG using protein-protein interaction network. Gene ontology items (490) and 68 Kyoto Encyclopedia of Genes and Genomes pathways were selected through the enrichment of target functions, including neuroactive ligand-receptor interaction, calcium signaling pathway, cAMP signaling pathway, Alzheimer disease, and serotonergic synapse that were related to Alzheimer's disease. Lastly, molecular docking demonstrated good stability in combining selected alkaloids with targets.</p><p><strong>Conclusions: </strong>This study explained the mechanisms of Amaryllidaceae alkaloids in preventing and treating Alzheimer's disease and established a novel strategy to discover new drugs from biological chemical sources.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"222-235"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289725","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":"Development of a pharmacokinetic/pharmacodynamic evaluation model for osteomyelitis and usefulness of tedizolid as an alternative to vancomycin against MRSA osteomyelitis.","authors":"Xiaoxi Liu, Yuki Enoki, Kazuaki Taguchi, Kazuaki Matsumoto","doi":"10.1093/jpp/rgae124","DOIUrl":"10.1093/jpp/rgae124","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to develop a suitable osteomyelitis model for pharmacokinetic/pharmacodynamic (PK/PD) evaluation and to investigate the target PK/PD values of vancomycin and tedizolid against methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis.</p><p><strong>Methods: </strong>An osteomyelitis model was established by implanting an MRSA-exposed sterilized suture in the tibia of normal mice and mice with cyclophosphamide-induced neutropenia. The suitability of the osteomyelitis mouse model for PK/PD evaluation was assessed using vancomycin as an indicator. The target PK/PD values for tedizolid were determined using this model.</p><p><strong>Key findings: </strong>In neutropenic mice, to achieve a static effect and 1 log10 kill against MRSA, the ratios of the area under the free drug concentration-time curve for 24 h to the minimum inhibitory concentration (fAUC24/MIC) of vancomycin were 91.29 and 430.03, respectively, confirming the validity of the osteomyelitis model for PK/PD evaluation. In immunocompetent mice, the target fAUC24/MIC values of tedizolid for achieving a static effect and 1 log10 kill against MRSA were 2.40 and 49.20, respectively. Additionally, only a 0.28 log10 kill was achieved in neutropenic mice with 20 times the human equivalent dose of tedizolid.</p><p><strong>Conclusions: </strong>In patients with restored immunity, tedizolid can potentially be used as an alternative to intravenous vancomycin therapy.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"291-298"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590863","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}
Wei Yu, Yaping Zhao, Iqra Ilyas, Li Wang, Peter J Little, Suowen Xu
{"title":"The natural polyphenol fisetin in atherosclerosis prevention: a mechanistic review.","authors":"Wei Yu, Yaping Zhao, Iqra Ilyas, Li Wang, Peter J Little, Suowen Xu","doi":"10.1093/jpp/rgae053","DOIUrl":"10.1093/jpp/rgae053","url":null,"abstract":"<p><p>The incidence and mortality rate of atherosclerotic cardiovascular disease (ASCVD) is increasing yearly worldwide. Recently, a growing body of evidence has unveiled the anti-atherosclerotic properties of fisetin, a natural polyphenol compound. In this article, we reviewed the pharmacologic actions of fisetin on experimental atherosclerosis and its protective effects on disease-relevant cell types such as endothelial cells, macrophages, vascular smooth muscle cells, and platelets. Based on its profound cardiovascular actions, fisetin holds potential for clinical translation and could be developed as a potential therapeutic option for atherosclerosis and its related complications. Large-scale randomized clinical trials are warranted to ascertain the safety and efficacy of fisetin in patients with or high risk for ASCVD.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"206-221"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908547","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}
Muhammad Asyraf Abduraman, Azimah Amanah, Shahrul Bariyah Sahul Hamid, Mohammad Farris Iman Leong Abdullah, Shaida Fariza Sulaiman, Mei Lan Tan
{"title":"The regulatory effects of mitragynine on P-glycoprotein transporter.","authors":"Muhammad Asyraf Abduraman, Azimah Amanah, Shahrul Bariyah Sahul Hamid, Mohammad Farris Iman Leong Abdullah, Shaida Fariza Sulaiman, Mei Lan Tan","doi":"10.1093/jpp/rgae131","DOIUrl":"10.1093/jpp/rgae131","url":null,"abstract":"<p><strong>Objectives: </strong>Kratom preparation containing Mitragyna speciosa Korth plant is frequently used as a recreational drug. Mitragynine, a major alkaloid isolated from M. speciosa, is often detected concurrently with other drugs during forensic analysis, indicating a safety concern. P-glycoprotein (P-gp) is a multidrug transporter. Modulation of P-gp transport activity by drugs or herbal compounds in the brain may lead to drug-herb interactions, resulting in neurotoxicity. We aim to determine the effects of mitragynine on the P-gp regulation and possible neurotoxicity.</p><p><strong>Methods: </strong>The effects of mitragynine on the P-gp regulation were investigated in human brain capillary endothelial cells (hCMEC/D3) using molecular docking and dynamic simulation and an optimized bidirectional transport assay, respectively. Repeated-dose treatment and neurotoxicity assessment were carried out using a blood-brain barrier model and polimerase chain reaction (PCR) array.</p><p><strong>Key findings: </strong>Mitragynine inhibits the P-gp transport activity via binding onto the nucleotide-binding domain site and forms a stable interaction with the P-gp protein complex. Nontoxic concentrations of mitragynine (<4 μM) and substrate drugs (0.001 μM) in the cells significantly enhanced endothelial cell permeability and elicited signs of neurotoxicity in PC-12 cells.</p><p><strong>Conclusions: </strong>Mitragynine is likely a P-gp inhibitor, hence concurrent administration of kratom products with P-gp substrates may lead to clinically significant interactions and neurotoxicity.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"321-334"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622680","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":"A prediction method for the individual serum concentration and therapeutic effect for optimizing adalimumab therapy in inflammatory bowel disease.","authors":"Koji Kimura, Atsushi Yoshida","doi":"10.1093/jpp/rgae092","DOIUrl":"10.1093/jpp/rgae092","url":null,"abstract":"<p><strong>Objectives: </strong>Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM's effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase.</p><p><strong>Methods: </strong>We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect.</p><p><strong>Results: </strong>Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient's final time point matched the observed effects in 9 of the 11 patients.</p><p><strong>Conclusion: </strong>This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"299-307"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620260","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}
Madiha Kanwal, Sadia Sarwar, Humaira Nadeem, Suad A Alghamdi, Abir Abdullah Alamro, Sumra Malik, Saima Maqsood, Amani A Alghamdi, Muhammad Junaid Tariq, Imran Malik, Arif Ullah Khan, Aleena Muskan
{"title":"Pyrazolone-nicotinic acid derivative (4Z)-4-(2-hydroxybenzylidine)-5-methyl-2-(pyridine-3-ylcarbonyl)-2, 4-dihydro-3H-pyrazole-3-one (IIc) as multitarget inhibitor of neurodegeneration and behavioural impairment in Dementia.","authors":"Madiha Kanwal, Sadia Sarwar, Humaira Nadeem, Suad A Alghamdi, Abir Abdullah Alamro, Sumra Malik, Saima Maqsood, Amani A Alghamdi, Muhammad Junaid Tariq, Imran Malik, Arif Ullah Khan, Aleena Muskan","doi":"10.1093/jpp/rgae075","DOIUrl":"10.1093/jpp/rgae075","url":null,"abstract":"<p><strong>Objective: </strong>The study was aimed at the synthesis and pharmacological investigation of (4Z)-4-(2-hydroxybenzylidine)-5-methyl-2-(pyridine-3-ylcarbonyl)-2, 4-dihydro-3H-pyrazole-3-one (IIc) in mice model of scopolamine-induced neurodegeneration and cognition impairment.</p><p><strong>Methods: </strong>The behavioural studies included Y-Maze Test, Water Morris Test, and Novel Object Recognition Test in Albino mice (20-25 g). Scopalamine was used as an inducing agent. The acetylcholinesterase (AChE) inhibitory assay was used to assess the role of the test compounds in vitro. The Crystal Violet Staining (Nissl staining) was used to assess the neuroprotective and antiapoptotic effect through quantifying the number of neurons and viability. The expression of the anti-inflammatory enzyme cyclooxygenase-2 (COX-2), cytokine tumour necrotic factor (TNF-α), key transcription factor producing pro-inflammatory signals nuclear factor kappa B (P-NFkB), and apoptosis marker p-JNK was validated through enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analysis. The tested compound reverted cognitive and behavioural impairment through inhibiting scopolamine-induced inflammation and oxidative stress.</p><p><strong>Key findings: </strong>We found that the compound IIc improved the short-term memory and learning behaviour of the experimental animals. Further investigation into molecular mechanisms showed that this effect was the manifestation of immunomodulatory, antioxidant, and consequently, of downsizing of inflammatory cytokines. These results were further validated through docking analysis.</p><p><strong>Conclusion: </strong>Finally, we conclude that the pyrazolone-nicotinic acid derivative IIc reversed the scopolamine-induced cognitive and behavioural deficits, attributed to acetylcholinesterase inhibition, neuronal recovery, antioxidant potential, and through downregulating the neuroinflammatory mediators p-NF-kB, cytokine TNF-α, and anti-inflammatory enzyme COX-2.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"275-290"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468357","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}
Ademola C Famurewa, Nupura Manish Prabhune, Sudharshan Prabhu
{"title":"Natural product mitigation of ferroptosis in platinum-based chemotherapy toxicity: targeting the underpinning oxidative signaling pathways.","authors":"Ademola C Famurewa, Nupura Manish Prabhune, Sudharshan Prabhu","doi":"10.1093/jpp/rgae132","DOIUrl":"10.1093/jpp/rgae132","url":null,"abstract":"<p><strong>Objectives: </strong>Platinum-based anticancer chemotherapy (PAC) represents a cornerstone in cancer treatment, retaining its status as the gold standard therapy. However, PAC's efficacy is countered by significant toxicities, such as nephrotoxicity, ototoxicity, and neurotoxicity. Recent studies have linked these toxicities to ferroptosis, characterized by iron accumulation, reactive oxygen species generation, and lipid peroxidation. This review explores the mechanisms underlying PAC-induced toxicities, focusing on the involvement of ferroptosis with three major PAC drugs-cisplatin, carboplatin, and oxaliplatin. Further, we provide a comprehensive analysis of the natural product mitigation of PAC-induced ferroptotic toxicity.</p><p><strong>Key findings: </strong>The mechanistic role of ferroptosis in cisplatin- and oxaliplatin-induced toxicities has been investigated, while studies on carboplatin-induced ferroptotic toxicities are lacking. Natural compounds targeting molecular pathways of ferroptosis have been explored to mitigate PAC-induced ferroptotic toxicity.</p><p><strong>Conclusion: </strong>While ferroptosis in cisplatin- and oxaliplatin-induced toxicities has been investigated, there remains a notable dearth of studies examining its involvement in carboplatin-induced toxicities. Hence, further exploration is warranted to define the role of ferroptosis in carboplatin-induced toxicities, and its further mitigation. Moreover, in-depth mechanistic evaluation is necessary to establish natural products evaluated against PAC-induced ferroptosis, as PAC adjuvants.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1-17"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562549","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":"Anti-liver cancer therapeutic targets and safety of usenamine A in experimental liver cancer.","authors":"Xiaoqiong He, Zhangping Zhou, Jing Wang, Qing Zhao, Shirui Fan, Qian Yao, Wenjing Lian, Yutong You","doi":"10.1093/jpp/rgae096","DOIUrl":"10.1093/jpp/rgae096","url":null,"abstract":"<p><strong>Background: </strong>Liver cancer is highly heterogeneous with poor drug response. Usenamine A has anticancer activity. Usnic acid has hepatocytotoxicity.</p><p><strong>Objectives: </strong>As a derivative of usnic acid, if usenamine A can be safely used in treatment for liver cancer is unknown.</p><p><strong>Methods: </strong>MTT and clone formation assays assessed cell viability and proliferation. Tumor growth was determined using a xenograft model. Flow cytometry was used to detect the cell cycle. mRNA transcriptome sequencing investigated differential gene expression. Safety was evaluated in mice.</p><p><strong>Key findings: </strong>Usenamine A inhibited proliferation and clone formation of HepG2 cells and xenograft tumor growth through cell cycle arrest at G0/G1. Usenamine A altered gene expression in a direction supporting anticancer activity. IL24, JUN, DUSP4, and DUSP5 were upregulated while PRKACA, PRKCB, TP53, WNT6, E2F3, LGR4, GPR78, and MAPK4 were downregulated. Ten of above genes overlapped in the KEGG enriched non-small cell lung cancer/glioma/cytokine-cytokine receptor interaction/Wnt/MAPK pathway network. Usenamine A has a strong binding affinity for PRKACA and PRKCB proteins. Usenamine A showed minimal toxicity in mice.</p><p><strong>Conclusions: </strong>Usenamine A is a safe anticancer agent against hepatocellular carcinoma. Regulation of 12 cancer-associated genes and the correlated pathway network are its therapeutic targets.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"43-55"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365641","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}
Hongxu Guan, Xiaoting Yang, Mingfeng Yang, Haitao Wang
{"title":"Targeting MAPK14 in microglial cells: neuroimmune implications of Panax ginseng in post-stroke inflammation.","authors":"Hongxu Guan, Xiaoting Yang, Mingfeng Yang, Haitao Wang","doi":"10.1093/jpp/rgae067","DOIUrl":"10.1093/jpp/rgae067","url":null,"abstract":"<p><strong>Aim: </strong>This study investigates the molecular mechanisms through which Panax ginseng and Panax notoginseng saponin (PNS) mitigate neuroinflammatory damage and promote neural repair postischemic stroke, utilizing bioinformatics, and experimental approaches.</p><p><strong>Background: </strong>Cerebral infarction significantly contributes to disability worldwide, with chronic neuroinflammation worsening cognitive impairments and leading to neurodegenerative diseases. Addressing neuroimmune interactions is crucial for slowing disease progression and enhancing patient recovery, highlighting the need for advanced research in neuroimmune regulatory mechanisms and therapeutic strategies.</p><p><strong>Objective: </strong>To elucidate the effects of the traditional Chinese medicine components Panax ginseng and PNS on neuroinflammatory damage following ischemic stroke, focusing on the molecular pathways involved in mitigating inflammation and facilitating neural repair.</p><p><strong>Methods: </strong>The study employs single-cell sequencing and transcriptomic analysis to investigate gene expression changes associated with cerebral infarction. Gene set enrichment analysis and weighted gene co-expression network analysis are used to identify key molecular markers and core genes. Furthermore, pharmacological profiling, including functional assays, assesses the impact of Ginsenoside-Rc, a PNS derivative, on microglial cell viability, cytokine production, and reactive oxygen species (ROS) levels.</p><p><strong>Results: </strong>Our analysis revealed that MAPK14 is a critical mediator in the neuroinflammatory response to ischemic stroke. Ginsenoside-Rc potentially targets and modulates MAPK14 activity to suppress inflammation. Experimental validation showed that Ginsenoside-Rc treatment, combined with MAPK14 silencing, significantly alters MAPK14 expression and mitigates neuroinflammatory damage, evidenced by reduced microglial cell death, inflammatory factor secretion, and ROS production.</p><p><strong>Conclusion: </strong>Ginsenoside-Rc's modulation of MAPK14 offers a promising therapeutic strategy for reducing neuroinflammation and potentially improving cognitive recovery post-ischemic stroke. This supports the therapeutic application of the traditional Chinese medicine Sanqi in ischemic stroke care, providing a theoretical and experimental foundation for its use.</p><p><strong>Others: </strong>Future work will focus on extending these findings through clinical trials to evaluate the efficacy and safety of Ginsenoside-Rc in human subjects, aiming to translate these promising preclinical results into practical therapeutic interventions for ischemic stroke recovery.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"170-187"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432205","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}