Pharmaceutical Biology最新文献

{"title":"Comparative efficacy and safety of Chinese patent medicines as an adjunctive therapy for diabetic peripheral neuropathy: systematic review and network meta-analysis of randomized controlled trials.","authors":"Qun Wang, Hui Xie, Zihong Wang, Runyun Huang, Min Xu, Yongjun Li, Lingling Shan, Hongyan Zhang, Xianghong Liu, Hongxing Zhang, Yunsheng Xu, Shiguang Sun","doi":"10.1080/13880209.2024.2422084","DOIUrl":"10.1080/13880209.2024.2422084","url":null,"abstract":"<p><strong>Context: </strong>Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Chinese patent medicines (CPMs) are widely used in clinical practice to treat DPN.</p><p><strong>Objective: </strong>This study aims to summarize the latest evidence on the harms and benefits of CPMs as adjunctive therapy for DPN.</p><p><strong>Materials and methods: </strong>We conducted searches for randomized controlled trials (RCTs) evaluating CPMs in conjunction with mecobalamin (Mec) or alpha-lipoic acid (αLA) across eight databases up to July 2024. The surface under the cumulative ranking area (SUCRA) was utilized to assess the clinical efficacy rate (CER), the peroneal motor nerve conduction velocity (pMNCV), the peroneal sensory nerve conduction velocity (pSNCV), the median motor nerve conduction velocity (mMNCV), and the median sensory nerve conduction velocity (mSNCV).</p><p><strong>Results: </strong>The search yielded 128 eligible studies with 31 CPMs with Mec and 39 eligible studies with 17 CPMs with αLA. SUCRA rankings indicated that, when combined with Mec, <i>Mailuoning</i> liquid (lMLN) was the most effective regimen for CER, <i>Honghua</i> injection (iHH) for pMNCV, <i>Maixuekang</i> capsule (cMXK) for pSNCV, <i>Dengzhanxixin</i> injection (iDZXX) for mMNCV, and <i>Tongxinluo</i> capsule (cTXL) for mSNCV. Combined with αLA, <i>Danhong</i> injection (iDH) showed the highest efficacy for CER, pSNCV, and mSNCV, while <i>Xueshuantong</i> injection (iXShT) was the most effective for pMNCV and mMNCV.</p><p><strong>Conclusion: </strong>This network meta-analysis confirms the efficacy and safety of 37 CPMs combined with Mec or αLA for treating DPN. However, given the potential risk of bias and the very low certainty of the evidence, these recommendations should be adopted with caution.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"833-852"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the anti-atherosclerosis mechanisms of Tanyu Tongzhi formula based on network pharmacology, Mendelian randomization, and experimental verification.","authors":"Jin Dai, Xinbin Zhou, Xiaoming Xu, Yuangang Qiu, Shenjie Chen, Wei Mao","doi":"10.1080/13880209.2024.2415666","DOIUrl":"10.1080/13880209.2024.2415666","url":null,"abstract":"<p><strong>Context: </strong>Tanyu Tongzhi Formula (TTF) exhibits potential against atherosclerosis; however, its mechanisms remain unclear.</p><p><strong>Objective: </strong>This study explores the pharmacological mechanisms of TTF in treating atherosclerosis.</p><p><strong>Materials and methods: </strong>Network pharmacology, molecular docking, mendelian randomization (MR), and liquid chromatography-mass spectrometry (LC-MS) analyses were utilized to reveal potential targets and compounds of TTF against atherosclerosis. After exploring the appropriate concentration of TTF to treat HCAECs using Cell Counting Kit-8 (CCK-8), the HCAECs were divided into three groups: control, oxidized low-density lipoprotein (ox-LDL, 50 μg/mL), and ox-LDL (50 μg/mL) + TTF (1 mg/mL). After 24-h incubation, the efficacy of TTF was verified by CCK-8, Oil red O staining, and ELISA. The expression of key targets was detected by real-time polymerase chain reaction (qPCR) and western blotting.</p><p><strong>Results: </strong>A total of 137 active compounds and 127 potential TTF targets against atherosclerosis were identified. MR identified ALB, TNF, PPARα, and PPARγ as key targets. Molecular docking indicated that baicalin, naringenin, and curcumin exhibited suitable binding activities to these targets, further confirming by LC-MS analysis. The IC₅₀ of TTF in HCAECs was 18.25 mg/mL. TTF treatment significantly improved atherosclerosis by enhancing cell viability, reducing lipid accumulation, and inhibiting inflammation factors (IL6, IL1B and TNF-α) in ox-LDL-treated HCAECs. Moreover, qPCR or western blotting indicated that TTF could up-regulate PPARα and PPARγ while down-regulate TNF expression.</p><p><strong>Discussion and conclusions: </strong>Our results revealed active compounds, key pathways, and core targets of TTF against atherosclerosis, providing experimental support for its application in treating of atherosclerosis.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"790-802"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic efficacy and pharmacological mechanism of Bailing capsule on chronic obstructive pulmonary disease: a meta-analysis and network pharmacology.","authors":"Guanzhou Ma, Yang Jin","doi":"10.1080/13880209.2024.2415643","DOIUrl":"10.1080/13880209.2024.2415643","url":null,"abstract":"<p><strong>Context: </strong>Bailing capsule, derived from <i>Cordyceps sinensis</i> (Berk.) Sacc. (Clavicipitaceae), has shown potential in the treatment of chronic obstructive pulmonary disease (COPD), a prevalent respiratory disorder.</p><p><strong>Objective: </strong>This study elucidates the efficacy and mechanism of action of the use of Bailing capsules in the treatment of COPD using meta-analysis and network pharmacology.</p><p><strong>Materials and methods: </strong>A meta-analysis of randomized controlled trials (RCTs) was performed. The treatment group received Bailing capsules alongside standard therapy, while the control group received standard therapy or in combination with other traditional Chinese medicines. Efficacy outcomes included lung function, exercise tolerance, acute exacerbation risk, and quality of life. Network pharmacology and molecular docking identified key targets of Bailing capsules.</p><p><strong>Results: </strong>The meta-analysis of 27 RCTs showed significant improvements in the treatment group for forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and the 6-min walk test (6MWT). Additionally, there was a marked reduction in acute COPD attacks and an improvement in quality of life. Meanwhile, network pharmacological analysis identified SRC, HIF1A, NFKB1, HDAC2, and PRKACA, as the potential core targets for Bailing capsules in the treatment of COPD.</p><p><strong>Discussion and conclusion: </strong>Bailing capsules have shown promising results in the treatment of stable COPD. Future studies should focus on large-scale, multicenter RCTs to confirm the long-term benefits and safety of Bailing capsules.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"803-817"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of a sensitive and reliable UPLC-MS/MS method to simultaneously quantify almonertinib and HAS-719 and its application to study the interaction with nicardipine.","authors":"Dongxin Chen, Jie Chen, Yuxin Shen, Xiaohai Chen, Hailun Xia, Ya-Nan Liu, Ren-Ai Xu","doi":"10.1080/13880209.2024.2425648","DOIUrl":"10.1080/13880209.2024.2425648","url":null,"abstract":"<p><strong>Context: </strong>Almonertinib is primarily metabolized by CYP3A4, so it could interact with a variety of drugs metabolized by CYP3A4, leading to the changes of systemic exposure.</p><p><strong>Objective: </strong>For the purpose of this experiment, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay with accuracy and simplicity was optimized and fully validated for the simultaneous quantitative determination of almonertinib and its metabolite HAS-719, and drug-drug interactions (DDI) between almonertinib and nicardipine <i>in vivo</i> and <i>in vitro</i> was researched.</p><p><strong>Materials and methods: </strong>Detection of analytes was achieved by UPLC-MS/MS coupled with multiple reaction monitoring (MRM) in the positive ion mode with ion transitions of <i>m/z</i> 526.01 → 72.04 for almonertinib, <i>m/z</i> 512.18 → 455.08 for HAS-719 and <i>m/z</i> 447.16 → 128.11 for IS, respectively.</p><p><strong>Results: </strong>There was favourable linearity in the 0.5-200 ng/mL calibration range for almonertinib and 0.5-100 ng/mL for HAS-719. The lower limit of quantification (LLOQ) for both analytes was 0.5 ng/mL. The precision, accuracy, stability, matrix effect and extraction recovery required for methodological validation were consistent with the requirements of FDA guideline. Then, the UPLC-MS/MS assay was employed successfully on the interactions of almonertinib and nicardipine <i>in vivo</i> and <i>in vitro</i>. The half-maximal inhibitory concentration (IC₅₀) was 1.19 μM in rat liver microsomes (RLM), where nicardipine inhibited the metabolism of almonertinib with a mixed inhibitory mechanism. In pharmacokinetic experiments of rats, it was observed that nicardipine could significantly alter the pharmacokinetic profiles of almonertinib, including AUC_(0-∞), AUC_(0-t) and C_max, but had no effect on the metabolism of HAS-719.</p><p><strong>Conclusion: </strong>According to the findings, it was indicated that nicardipine could inhibit the metabolism of almonertinib <i>in vitro and in vivo</i>.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"874-881"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms underlying Tao-Hong-Si-Wu decoction treating hyperpigmentation based on network pharmacology, Mendelian randomization analysis, and experimental verification.","authors":"Jun Chen, Wenyi Ye","doi":"10.1080/13880209.2024.2330609","DOIUrl":"10.1080/13880209.2024.2330609","url":null,"abstract":"<p><strong>Context: </strong>Hyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options.</p><p><strong>Objective: </strong>This study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms.</p><p><strong>Materials and methods: </strong>We employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD's hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an <i>in vitro</i> hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting.</p><p><strong>Results: </strong>ALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC₅₀) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells.</p><p><strong>Discussion and conclusion: </strong>THSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"296-313"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detoxification of paraoxon-ethyl by <i>Lysiphyllum strychnifolium</i> extracts in undifferentiated human neuroblastoma SH-SY5Y cells.","authors":"Niramai Ekaratcharoenchai, Thararat Nualsanit, Aungkana Krajarng","doi":"10.1080/13880209.2024.2430262","DOIUrl":"10.1080/13880209.2024.2430262","url":null,"abstract":"<p><strong>Context: </strong><i>Lysiphyllum strychnifolium</i> (Craib) A. Schmitz. (Fabaceae) is a Thai traditional medicine used to remove food and alcohol toxins from the body.</p><p><strong>Objective: </strong>This study investigates the molecular mechanism of <i>L. strychnifolium</i> extracts against paraoxon-ethyl-induced apoptosis in SH-SY5Y cells.</p><p><strong>Materials and methods: </strong>The ethanol and water extracts of leaves and stems of <i>L. strychnifolium</i> were prepared at various concentrations (0-100 μg/mL) and co-treated to the cells with 0.375 mM paraoxon-ethyl for 24 and 48 h. Cell viability was performed using the PrestoBlue assay. ROS and caspase activity were detected using 2',7'-dichlorodihydrofluorecein diacetate and caspase-Glo® 3/7, 8, and 9 assay kits. Apoptotic and ER stress-related gene expression were determined by real-time PCR, and nuclear and mitochondrial morphology were observed using Hoechst 33342 and MitoTracker® Deep Red FM staining.</p><p><strong>Results: </strong>The most effective concentrations of each extract against paraoxon-ethyl-induced cell death were 25 μg/mL of leaf ethanol, 12.5 μg/mL of stem ethanol, 100 μg/mL of leaf water, and 25 μg/mL of stem water extracts. The leaf ethanol extract was the most effective at detoxifying, while stem extracts were highly toxic in high doses. The detoxifying <i>L. strychnifolium</i> extracts against paraoxon-ethyl-induced oxidative stress decreased <i>p53, BiP/GRP78</i>, and <i>CHOP</i> gene expression and minimized caspase 9 and caspase 3, protecting cells from apoptosis. The extracts could also restore mitochondrial membrane potential and reduce the swollen globule mitochondrial shape.</p><p><strong>Discussion and conclusion: </strong>These findings could potentially protect neuron cells from neurodegenerative issues due to oxidative damage, apoptosis, and other potential consequences.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"882-891"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Qing Hua Chang Yin ameliorates chronic colitis in mice by inhibiting PERK-ATF4-CHOP pathway of ER stress and the NF-κB signalling pathway.","authors":"Liya Liu, Youqin Chen, Yuying Han, Xinran Zhang, Yulun Wu, Jing Lin, Liujing Cao, Meizhu Wu, Huifang Zheng, Yi Fang, Lihui Wei, Thomas J Sferra, Anjum Jafri, Xiao Ke, Jun Peng, Aling Shen","doi":"10.1080/13880209.2024.2378012","DOIUrl":"10.1080/13880209.2024.2378012","url":null,"abstract":"<p><strong>Context: </strong>Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted.</p><p><strong>Objective: </strong>To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms.</p><p><strong>Materials and methods: </strong>A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups (<i>n</i> = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining.</p><p><strong>Results: </strong>Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1β and TNF-α. QHCY suppressed the activation of PERK-ATF4-CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues.</p><p><strong>Discussion and conclusions: </strong>The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"607-620"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of total coumarins from <i>Pileostegia tomentella</i> on exosomal miRNA expression and angiogenesis in colorectal cancer cells.","authors":"Ying Liu, Dao-Hai Cheng, Zheng-Ying Su, Ji-Hua Lv, Li Wang, Yu-Yin Deng, Li Li","doi":"10.1080/13880209.2024.2309871","DOIUrl":"10.1080/13880209.2024.2309871","url":null,"abstract":"<p><strong>Context: </strong><i>Pileostegia tomentella</i> Hand. Mazz (Saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. Tumour angiogenesis mediated by exosomes-derived miRNA exhibits the vital regulation of endothelial cell function in metastasis of CRC.</p><p><strong>Objective: </strong>To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.</p><p><strong>Materials and methods: </strong>HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/mL) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. Co-culture experiments for human umbilical vein endothelial cells (HUVECs) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNAs in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNA into HUVECs.</p><p><strong>Results: </strong>HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 and VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in Exo-TCPT. Rescue assays showed that high expression of miR-375-3p in HUVECs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects.</p><p><strong>Discussion and conclusion: </strong>TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of <i>Pileostegia tomentella</i> in CRC.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"153-161"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10866057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and biological evaluation of novel podophyllotoxin derivatives as tubulin-targeting anticancer agents.","authors":"Yujin Guo, Beibei Chen, Jinxiu Guo, Pei Jiang, Jianhua Wang, Wenxue Sun","doi":"10.1080/13880209.2024.2318350","DOIUrl":"10.1080/13880209.2024.2318350","url":null,"abstract":"<p><strong>Context: </strong>Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.</p><p><strong>Objective: </strong>This study synthesizes PPT derivatives to assess their anticancer activities.</p><p><strong>Materials and methods: </strong>Compounds E1-E16 antiproliferative activity was tested against four human cancer cell lines (H446, MCF-7, HeLa, A549) and two normal cell lines (L02, BEAS-2B) using the CCK-8 assay. The effects of compound <b>E5</b> on A549 cell growth were evaluated through molecular docking, <i>in vitro</i> assays (flow cytometry, wound healing, Transwell, colony formation, Western blot), and <i>in vivo</i> tests in female BALB/c nude mice treated with <b>E5</b> (2 and 4 mg/kg). <b>E5</b> (4 mg/kg) significantly reduced xenograft tumor growth compared to the DMSO control group.</p><p><strong>Results: </strong>Among the 16 PPT derivatives tested for cytotoxicity, <b>E5</b> exhibited potent effects against A549 cells (IC₅₀: 0.35 ± 0.13 µM) and exceeded the reference drugs PPT and etoposide to inhibit the growth of xenograft tumours. <b>E5</b>-induced cell cycle arrest in the S and G2/M phases accelerated tubulin depolymerization and triggered apoptosis and mitochondrial depolarization while regulating the expression of apoptosis-related proteins and effectively inhibited cell migration and invasion, suggesting a potential to limit metastasis. Molecular docking showed binding of <b>E5</b> to tubulin at the colchicine site and to Akt, with a consequent down-regulation of PI3K/Akt pathway proteins.</p><p><strong>Discussion and conclusions: </strong>This research lays the groundwork for advancing cancer treatment through developing and using PPT derivatives. The encouraging results associated with <b>E5</b> call for extended research and clinical validation, leading to novel and more effective cancer therapies.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"233-249"},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proanthocyanidin offers protection against diabetic nephropathy: elucidation of its mechanism of action using animal models.","authors":"Dengpiao Xie, Huan Wang, Qing Ji, Jianting Wang","doi":"10.1080/13880209.2024.2409772","DOIUrl":"10.1080/13880209.2024.2409772","url":null,"abstract":"<p><strong>Context: </strong>Diabetic nephropathy (DN) is a major complication of diabetes mellitus and is the leading cause of kidney disease in patients undergoing renal replacement therapy. DN is associated with an increased risk of death in patients with diabetes. Conventional therapy for DN includes intensive control of blood glucose level and blood pressure and renin-angiotensin system blockade. However, this approach has limited treatment effects on DN. Therefore, identifying novel drugs to delay the progression of DN is urgently needed. Proanthocyanidin (PA) has been shown to exert potentially beneficial effects on DN. However, the protective mechanism and efficacy are yet to be elucidated.</p><p><strong>Objective: </strong>This study evaluates the efficacy and potential mechanisms of PA in animal models of DN.</p><p><strong>Methods: </strong>Preclinical studies were searched from Chinese National Knowledge Infrastructure, PubMed, Web of Science, Embase, and Google Scholar databases, with the search deadline of August 2023. Keywords ('diabetic nephropathies', 'nephropathies, diabetic', 'diabetic kidney diseases', 'proanthocyanidin', 'anthocyanidin polymers', 'procyanidins', 'animal*', 'rat', and 'mice') were used to search the databases. RevMan 5.3 was used for statistical analysis.</p><p><strong>Results: </strong>A total of 22 studies involving 538 animals were included in this analysis. The pooled results indicated that PA therapy significantly improved kidney function and reduced proteinuria and blood glucose levels. The protective mechanism of PA was associated with anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic effects; inhibition of endoplasmic reticulum stress; and alleviation of mitochondrial dysfunction and dyslipidemia.</p><p><strong>Conclusion: </strong>These findings suggest that PA alleviates DN by mediating multiple targets and pathways.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"702-712"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}