Journal of Pharmacy and Pharmacology最新文献

{"title":"The mechanism of action of Botrychium (Thunb.) Sw. for prevention of idiopathic pulmonary fibrosis based on 1H-NMR-based metabolomics.","authors":"Yutao Lou, Xiaozhou Zou, Zongfu Pan, Zhongjie Huang, Shuilian Zheng, Xiaowei Zheng, Xiuli Yang, Meihua Bao, Yuan Zhang, Jinping Gu, Yiwen Zhang","doi":"10.1093/jpp/rgae058","DOIUrl":"10.1093/jpp/rgae058","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to reveal the anti-fibrotic effects of Botrychium ternatum (Thunb.) Sw. (BT) against idiopathic pulmonary fibrosis (IPF) and to preliminarily analyze its potential mechanism on bleomycin-induced IPF rats.</p><p><strong>Methods: </strong>The inhibition of fibrosis progression in vivo was assessed by histopathology combined with biochemical indicators. In addition, the metabolic regulatory mechanism was investigated using 1H-nuclear magnetic resonance-based metabolomics combined with multivariate statistical analysis.</p><p><strong>Key findings: </strong>Firstly, biochemical analysis revealed that BT notably suppressed the expression of hydroxyproline and transforming growth factor-β1 in the pulmonary tissue. Secondly, Masson's trichrome staining and hematoxylin and eosin showed that BT substantially improved the structure of the damaged lung and significantly inhibited the proliferation of collagen fibers and the deposition of extracellular matrix. Finally, serum metabolomic analysis suggested that BT may exert anti-fibrotic effects by synergistically regulating tyrosine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and synthesis and degradation of ketone bodies.</p><p><strong>Conclusions: </strong>Our study not only clarifies the potential anti-fibrotic mechanism of BT against IPF at the metabolic level but also provides a theoretical basis for developing BT as an effective anti-fibrotic agent.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1018-1027"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080766","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":"Wedelolactone suppresses breast cancer growth and metastasis via regulating TGF-β1/Smad signaling pathway.","authors":"Hui Li, Manting Hou, Ping Zhang, Lutong Ren, Yuanyuan Guo, Liang Zou, Junling Cao, Zhaofang Bai","doi":"10.1093/jpp/rgae065","DOIUrl":"10.1093/jpp/rgae065","url":null,"abstract":"<p><strong>Objective: </strong>Breast cancer is a malignant tumor with high invasion and metastasis. TGF-β1-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of breast cancer. Wedelolactone (Wed) is extracted from herbal medicine Ecliptae Herba, which is reported to have antineoplastic activity. Here, we aimed to elucidate the efficacy and mechanism of Wed against breast cancer.</p><p><strong>Methods: </strong>The effects of Wed on migration and invasion of 4T1 were detected. The expression of EMT-related markers was detected by Western blot and qPCR. The 4T1 orthotopic murine breast cancer model was established to evaluate the therapeutic effect of Wed on the growth and metastasis of breast cancer through TGF-β1/Smad pathway.</p><p><strong>Results: </strong>Wed inhibited the proliferation, migration and invasion of 4T1. It exhibited concentration-dependent inhibition of p-Smad2/3. Wed also reversed the expression of EMT-markers induced by TGF-β1. In addition, Wed suppressed the growth and metastasis of breast cancer in mice. It also affected p-Smad3 expression as well as EMT-related genes, suggesting that its anti-breast cancer effect may be related to the TGF-β1/Smad pathway.</p><p><strong>Conclusion: </strong>Wed reverses EMT by regulating TGF-β1/Smad pathway, potentially serving as a therapeutic agent for breast cancer. Wed is expected to be a potential drug to inhibit TGF-β1/Smad pathway-related diseases.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"1038-1050"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288281","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 potential of 4-dimethylamino chalcone against acute and neuropathic pain in mice.","authors":"Isabela Souza Dos Santos Marchon, Evelynn Dalila do Nascimento Melo, Mirella da Costa Botinhão, Greice Nascimento Pires, João Vitor Rocha Reis, Rodrigo Octavio Mendonça Alves de Souza, Ivana Correa Ramos Leal, André Gustavo Calvano Bonavita, Henrique Rocha Mendonça, Michelle Frazão Muzitano, Leandro Louback da Silva, Paula Lima do Carmo, Juliana Montani Raimundo","doi":"10.1093/jpp/rgae057","DOIUrl":"10.1093/jpp/rgae057","url":null,"abstract":"<p><strong>Objectives: </strong>This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice.</p><p><strong>Methods: </strong>The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC. VIPN was induced through the administration of vincristine sulphate (0.1 mg/kg, i.p., 14 days). Then, DMSO, DMAC (10 or 30 mg/kg; i.p.), or pregabalin (10 mg/kg, i.p.) were administered for 14 consecutive days. Thermal hyperalgesia and mechanical allodynia were evaluated before and after VIPN induction and on days 1, 3, 7, and 14 of treatment. Neurodegeneration and neuroinflammation were assessed through immunohistochemistry for NF200, iNOS, and arginase-1 within the sciatic nerve.</p><p><strong>Key findings: </strong>DMAC inhibited myeloperoxidase activity in vitro and presented an acute antinociceptive effect in both formalin and hot plate tests, with the involvement of muscarinic and opioid receptors. Treatment with 30 mg/kg of DMAC significantly attenuated thermal hyperalgesia and mechanical allodynia and prevented macrophage proinflammatory polarisation in VIPN mice.</p><p><strong>Conclusions: </strong>Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"983-994"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908544","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":"Erythrocyte membrane-camouflaged mesoporous silica composite nanoparticles for loading and controlled release of the hepatoprotective agent silibinin: A-synthesis and physicochemical characterization.","authors":"Vahid Tayebi Khorrami, Mohammad Javad Raee, Samira Sadat Abolmaali, Mozhgan Abedanzadeh, Mina Shafiee, Ali Mohammad Tamaddon","doi":"10.1093/jpp/rgae046","DOIUrl":"10.1093/jpp/rgae046","url":null,"abstract":"<p><strong>Objectives: </strong>Milk thistle has long been used in the treatment of liver and biliary disorders. In the present study, to make a long-acting delivery system for silibinin (SBN, a major active constituent of milk thistle seeds with antioxidant and hepatoprotective function), mesoporous silica composite nanoparticles (NC) were synthesized and coated with RBC membrane.</p><p><strong>Methods: </strong>A modified Stöber method was used for NC synthesis, which was then characterized using FE-SEM, DLS, TEM, FTIR, and EDAX techniques. A suitable lysis buffer was used to prepare RBC-ghost, and sonication was used to coat SBN-loaded NC (SBN-NC). The RBC-ghost coated SBN-NC (SBN-NC-RBCG) was evaluated by SDS-PAGE, Bradford, TEM, EDAX, and DLS methods. SBN release was then compared for the SBN-NC and SBN-NC-RBCG samples.</p><p><strong>Key findings: </strong>the RBC membrane proteins were recovered from the coating of SBN-NC-RBCG, and SBN release was sustained over 24 h when compared with the SBN-NC.</p><p><strong>Conclusions: </strong>Overall, through prolonging circulation in the bloodstream and evading the immune system, the developed system can improve SBN bioavailability in liver inflammation and fibrosis conditions that need further research.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"995-1005"},"PeriodicalIF":2.8,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066001","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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-23","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":"Case study: cremophor EL-based liquid formulations as simple substitutes for amorphous solid dispersions in early preclinical in vivo studies.","authors":"Kalle Sigfridsson, Xiang Zhang, Antonio Llinas","doi":"10.1093/jpp/rgae099","DOIUrl":"https://doi.org/10.1093/jpp/rgae099","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of the present case study was to increase the exposure of the poorly soluble crystalline compound A.</p><p><strong>Methods: </strong>Mice received 10 mg/kg of crystalline compound A formulated in eight different cosolvent, oil, and cyclodextrin mixtures.</p><p><strong>Key findings: </strong>In all cases, AUC0-24h and maximum blood/plasma concentration (Cmax) were in the range of 6-16 µM × h and <1.4 µm, respectively, with a bioavailability below 18%. When 6% cremophor (CrEL) was added to three selected vehicles, AUC0-24h and Cmax increased ~5-10 times. The obtained pharmacokinetic profile of the most improved formulation using CrEL was possible to superimpose on the one obtained after administration of a CrEL-free amorphous solid dispersion (ASD, HPMC-AS:drug, 80:20) suspension of compound A.</p><p><strong>Conclusions: </strong>It is crucial to find an optimal screen vehicle as early as possible for a poorly water-soluble lead series and then avoid time and resource-consuming vehicle testing of multiple compounds in vivo. An ASD approach is more suited for clinical development when more time and resources are allocated to the project. In this case study, some preclinical formulations were used to maximize exposure but also as preindicators for ASDs later in the development chain.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751972","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":"Croton grewioides essential oil and anethole reduce oxidative stress and improve growth of bovine primordial follicles during culture of ovarian tissue.","authors":"Felipe F da Silva, Francisco das Chagas Costa, Venância A N Azevedo, Ernando I T de Assis, Geovany A Gomes, Valdevane R Araújo, Selene M de Morais, Tigressa H S Rodrigues, José R V Silva","doi":"10.1093/jpp/rgae093","DOIUrl":"https://doi.org/10.1093/jpp/rgae093","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to evaluate the effects of Croton grewioides essential oil (CGEO) and anethole on follicle survival, growth, and oxidative stress in cultured bovine ovarian tissues.</p><p><strong>Methods: </strong>Ovarian tissues were cultured for 6 days in a medium supplemented with different concentrations (1, 10, 100, or 1000 µg mL-1) of CGEO or anethole and then, follicular survival and growth, collagen content, and stromal cell density in ovarian tissues cultured in vitro were evaluated by histology. The mRNA levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 1 (GPX1), peroxirredoxin 6 (PRDX6), and nuclear factor erythroid 2-related factor 2 (NRF2) were evaluated by real-time PCR. The activity of SOD, CAT, glutathione peroxidase (GPx), and thiol concentrations were investigated.</p><p><strong>Key findings: </strong>Ovarian tissues cultured with 1 µg mL-1 CGEO or anethole had a higher percentage of healthy follicles than those cultured in a control medium (P < .05). The 1 µg mL-1 CGEO also increased the number of stromal cells, collagen fibers, and thiol levels. Anethole (1 µg mL-1) increased CAT activity and reduced that of GPx. The activity of SOD was reduced by CGEO. In contrast, 1 µg mL-1 anethole reduced mRNA for CAT, PRDX1, and NRF2 (P < .05). In addition, 1 µg mL-1 CGEO reduced mRNA for CAT, PRDX6, and GPx1 (P < .05).</p><p><strong>Conclusions: </strong>The presence of 1 µg mL-1 anethole or CGEO in a culture medium promotes follicle survival and regulates oxidative stress and the expression of mRNA and activity of antioxidant enzymes in cultured bovine ovarian tissues.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627029","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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-16","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":"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":"https://doi.org/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":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-15","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":"Protopanaxadiol prevents cisplatin-induced acute kidney injury by regulating ferroptosis.","authors":"Zeyu Song, Zhenyuan Li, Tao Pan, Teng Liu, Baifang Gong, Zhixia Wang, Ke Liu, Huaying Fan","doi":"10.1093/jpp/rgae050","DOIUrl":"10.1093/jpp/rgae050","url":null,"abstract":"<p><strong>Objectives: </strong>Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms.</p><p><strong>Methods: </strong>In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins.</p><p><strong>Results: </strong>PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system.</p><p><strong>Conclusion: </strong>PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"884-896"},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857339","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}