Journal of Pharmacy and Pharmacology最新文献

{"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}

{"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}

{"title":"Exploration of medicinal plants as potential therapeutics against COVID-19: molecular insights and drug development prospects with other significant medicinal information a retrospective exposition.","authors":"Saurabh Dilip Bhandare","doi":"10.1093/jpp/rgae074","DOIUrl":"10.1093/jpp/rgae074","url":null,"abstract":"<p><strong>Objectives: </strong>The study aims to explore the potential of medicinal plants and their phytoconstituents as effective inhibitors of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus. The focus is on investigating specific medicinal plants known for their pharmacological properties, such as: antioxidant, anti-inflammatory, and immunomodulatory effects, to determine their viability in developing COVID-19 treatments.</p><p><strong>Materials and methods: </strong>This study involves a comprehensive study of medicinal plants, including: Withania somnifera (Ashwagandha) and Ocimum sanctum (Holy Basil), known for their beneficial health effects. Molecular docking studies were conducted to assess the interactions between phytoconstituents from these plants and SARS-CoV-2 proteins. The compounds' drug-like characteristics and safety profiles were also evaluated to determine their potential as therapeutic agents.</p><p><strong>Results: </strong>The molecular docking studies revealed that the phytoconstituents from the studied medicinal plants exhibit favourable interactions with SARS-CoV-2 proteins, suggesting their potential as therapeutic targets. These compounds demonstrated promising drug-like characteristics and safety profiles, indicating their suitability for further development as COVID-19-fighting medications.</p><p><strong>Discussion: </strong>The results indicate that medicinal plants and their bioactive substances hold significant potential for developing therapies against COVID-19. The ability of these organic substances to interact with key viral proteins and provide various therapeutic benefits highlights their potential as multi-functional treatment options. However, further research is necessary to confirm these findings and to understand the full scope of their therapeutic efficacy and safety in clinical settings.</p><p><strong>Conclusions: </strong>Medicinal plants and their phyto-constituents represent a promising avenue for developing effective treatments for COVID-19. The favourable interactions with SARS-CoV-2 proteins and the promising drug-like characteristics observed in this study suggest that these natural compounds could be integral in the fight against the COVID-19 pandemic. Further research and clinical trials are essential to fully validating their potential and translating these findings into practical medical applications.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"18-31"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036060","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":"Frondoside A of Cucumaria frondosa (Gennerus, 1767): Chemistry, biosynthesis, medicinal applications, and mechanism of actions.","authors":"Oladapo F Fagbohun, Amanda Rollins, Lindsey Mattern, Kendra Cipollini, Hp Vasantha Rupasinghe","doi":"10.1093/jpp/rgae059","DOIUrl":"10.1093/jpp/rgae059","url":null,"abstract":"<p><p>Cucumaria frondosa (Gennerus, 1767) or orange-footed sea cucumbers are traditional food and are used as natural sources of anti-diabetic, anti-inflammatory, antioxidant, anti-angiogenic, antimicrobial, and anticancer agents. Currently, the introduction of value-added sea cucumber products to the global market has inspired basic research on frondoside A and other saponins in sea cucumbers. These saponins serve as a means of their chemical defence. However, recent studies revealed that exposure to these saponins can lead to irritating symptoms from aerosolization of various holothurins. Moreover, extraction methods are critical to the bioavailability of various bioactive compounds found in sea cucumbers. Therefore, we have critically reviewed recent studies on the chemistry, biosynthesis, and pharmacological properties of frondoside A. Furthermore, the mechanism of actions of frondoside A was postulated and further studies are required for applications in functional foods, nutraceuticals, and pharmaceuticals. Frondoside A was first discovered from Cucumaria frondosa, and it is involved in protein kinase (PI3K/AKT/ERK1/2/p38 MAPK, RAC/CDC42 PAK1, NFκB/MAPK/JNK, and LXR-β) signalling pathways. It is also involved in the suppression of MYC oncogene transcriptional factors implicated and upregulated in over 70% of cancer types. Future research needs to be aimed at optimized green extraction techniques, efficient delivery methods, safety, and efficacy.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"32-42"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283961","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":"Pharmacological investigation of genistein for its therapeutic potential against nitroglycerin-induced migraine headache.","authors":"Qirrat Sajjad, Arif-Ullah Khan, Aslam Khan","doi":"10.1093/jpp/rgae084","DOIUrl":"10.1093/jpp/rgae084","url":null,"abstract":"<p><strong>Objectives: </strong>Migraine, typically occurs on one side of the head, lasts for hours to days. Trigemino-vascular system (TVS) plays a vital role in pain generation, with neurogenic inflammation and oxidative stress playing key roles in its pathophysiology.</p><p><strong>Methods: </strong>This study aimed to investigate genistein's potential as anti-inflammatory and anti-oxidant agent in mitigating migraine pain. Genistein (20 and 50 mg/kg) was administered intraperitoneally (IP) to nitroglycerin (NTG; 10 mg/kg)-induced migraine model in rats. Behavioral analysis, antioxidant assay, immunohistochemistry (IHC), histopathological examination, ELISA, and RT-PCR were conducted to evaluate the antimigraine potential of genistein.</p><p><strong>Key findings: </strong>In-silico analysis showed genestien's ACE values of -4.8 to -9.2 Kcal/mol against selected protein targets. Genistein significantly reversed mechanical and thermal nociception, light phobicity, and head scratching; increased the intensities of GST, GSH, catalase; and down regulated lipid peroxidase (LPO) in cortex and trigeminal nucleus caudalis (TNC). It also reduced Nrf2, NF-kB, and IL6 expression, analyzed through IHC, improved histopathological features, and increased COX-2 and decreased PPAR-γ expressions, while RT-PCR analysis revealed increased PPAR-γ expressions in genistein-treated rats.</p><p><strong>Conclusion: </strong>Genistein exhibited potent antioxidant and anti-inflammatory properties in migraine treatment, acting through multifactorial mechanisms by modulating the expression of numerous proteins in the region cortex and TNC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"76-94"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620261","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":"Psidium guajava leaves extract alters colonic microbiome composition and reduces intestinal sodium absorption in rats exposed to a high-sodium diet.","authors":"Daiane Cristina de Assis Braga, Marcos Adriano Carlos Batista, Renata Guerra-Sá, Thayane Christine Alves da Silva, Marco Antônio Alves Carneiro, Maria Célia da Silva Lanna, Vasco Ariston Azevedo, Rodrigo Dias de Oliveira Carvalho, Gustavo Henrique Bianco de Souza, Vagner Roberto Antunes, Sandra Aparecida Lima de Moura, Carla Speroni Ceron, Leonardo Máximo Cardoso","doi":"10.1093/jpp/rgae137","DOIUrl":"10.1093/jpp/rgae137","url":null,"abstract":"<p><strong>Objectives: </strong>High sodium intake is a major risk factor for hypertension and renal diseases. Previous studies have shown that a suspension of ethanolic extract of Psidium guajava (guava) leaves (PsE) has antihypertensive effects in rats on a high-sodium diet (HSD), but some mechanisms to that remain unexplored. This study explored whether oral PsE treatment affects sodium handling by the intestine and alters the gut microbiome in HSD-fed rats.</p><p><strong>Methods: </strong>Male Wistar rats were divided into two groups: standard salt diet (SSD) and HSD (0.9% Na+), from weaning. After 12 weeks, both groups received PsE (200 mg/kg) or a vehicle for an additional 4 weeks.</p><p><strong>Key findings: </strong>Sodium excretion was measured using flame photometry, and sodium absorption was assessed by intestinal perfusion technique. The gut microbiome was analysed through 16S ribosomal gene sequencing. HSD increased faecal sodium, further elevated by PsE, which inhibited intestinal sodium absorption in HSD rats. HSD altered the abundance of specific bacterial families, which PsE partially reversed. No changes in alpha diversity were noted among groups.</p><p><strong>Conclusions: </strong>These findings suggest that PsE inhibited intestinal sodium handling and that PsE, combined with increased faecal sodium, may reshape the gut microbiome of HSD rats to resemble that of SSD rats.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"111-126"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604603","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":"Serum autotaxin level: a promising diagnostic biomarker in differentiating Graves' disease and thyroiditis.","authors":"Angel George, Anns Mariya, Manu Eappen, Marimuthu Karthikeyan, Ravindranath Sreenath","doi":"10.1093/jpp/rgae073","DOIUrl":"10.1093/jpp/rgae073","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have suggested that serum autotaxin (ATX) may be a promising diagnostic biomarker in differentiating between Graves' disease (GD) and thyroiditis, as well as serving as a monitoring biomarker for GD. This study will evaluate the use of serum ATX as a diagnostic biomarker in these conditions.</p><p><strong>Methods: </strong>In this prospective interventional study, blood samples were collected from the patients who met both inclusion and exclusion criteria, and serum ATX levels were measured by using the MyBioSource human Autotaxin ELISA kit.</p><p><strong>Results: </strong>A total of 32 patients were enrolled, of which 18.8% were newly diagnosed with GD, 21.9% were thyroiditis, and 59.3% were on treatment for GD. Serum autotaxin antigen was significantly higher in GD patients than in thyroiditis (603.3217 ± 444.24 v/s 214.74 ± 55.91, P = <.005). Serum ATX measurement successfully discriminated GD patients from thyroiditis (AUC = 0.952, 95%CI: 0.00-1.00) with an optimal cutoff value of ≥257.20 ng/L (sensitivity = 100 and specificity = 81.71). Monitoring the efficacy of serum ATX was analyzed and showed a significant difference.</p><p><strong>Conclusion: </strong>The serum ATX was higher in subjects with GD as compared to thyroiditis, and ATX levels were found to be decreased during the treatment period. In conclusion, serum ATX can be used as a diagnostic and monitoring biomarker in GD.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"56-63"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723805","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":"Super-enhancer-driven ameboidal-type cell migration-related MMP14 expression in tongue squamous cell carcinoma switched by BATF and ATF3.","authors":"Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang","doi":"10.1093/jpp/rgae063","DOIUrl":"10.1093/jpp/rgae063","url":null,"abstract":"<p><strong>Background: </strong>Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.</p><p><strong>Methods: </strong>Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.</p><p><strong>Results: </strong>Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.</p><p><strong>Conclusion: </strong>SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"64-75"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248278","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":"Deciphering farnesol's anti-arthritic and immunomodulatory potential by targeting multiple pathways: a combination of network pharmacology guided exploration and experimental verification.","authors":"Shaimaa R Ahmed, Ambreen Malik Uttra, Muhammad Usman, Sumera Qasim, Shah Jahan, Muhammad Roman, Hanan Khojah, Omnia Hendawy, Eman K Rashwan","doi":"10.1093/jpp/rgae126","DOIUrl":"10.1093/jpp/rgae126","url":null,"abstract":"<p><strong>Objective: </strong>Farnesol (FAR), a sesquiterpene alcohol, has documented FAR's anti-inflammatory and antioxidant activities. Current study was undertaken to assess the efficacy and mechanism of FAR in arthritis by employing network pharmacology and experimental models.</p><p><strong>Methods: </strong>Two experimental models comprising formaldehyde- and complete Freund's adjuvant (CFA)-induced arthritis evaluated the efficacy of FAR in treating arthritis. Various parameters were assessed. Then, a network pharmacology approach was applied to gain further insight into the potential mechanism and signaling pathways.</p><p><strong>Key findings: </strong>FAR significantly reduced paw volume and the arthritic score and improved the hematological and biochemical changes. Radiographic and histological examination showed the anti-arthritic efficacy of FAR, which was associated with down-regulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Network pharmacology analysis revealed that FAR may exert its anti-arthritic effects by targeting specific genes associated with arthritis. Pathway analysis revealed the involvement of three key signaling pathways (IL-17 signaling, TNF signaling, and toll-like receptor signaling) in the development and progression of arthritis.</p><p><strong>Conclusions: </strong>The results pointed out the protective attributes of farnesol against formaldehyde and CFA-induced arthritis via modulation of multiple targets. This study provides a valuable reference for the development of a new treatment or complementary therapy for arthritis.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"127-141"},"PeriodicalIF":2.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391387","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}