Journal of Pharmacy and Pharmacology最新文献

{"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}

{"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}

{"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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-29","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":"Repurposing the familiar: Future treatment options against chronic kidney disease.","authors":"Rohan Bhadange, Anil Bhanudas Gaikwad","doi":"10.1093/jpp/rgaf002","DOIUrl":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-20","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":"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}