Combinatorial chemistry & high throughput screening最新文献

{"title":"Antiproliferative Activity of Cephalotaxus Esters: Overcoming Chemoresistance.","authors":"Vladimir Yong-Gonzalez, Constantin Radu, Paul A Calder, David Shum, David Y Gin, Mark G Frattini, Hakim Djaballah","doi":"10.2174/0113862073322175240823104921","DOIUrl":"https://doi.org/10.2174/0113862073322175240823104921","url":null,"abstract":"<p><strong>Introduction: </strong>Omacetaxine, a semisynthetic form of Homoharringtonine (HHT), was approved for the treatment of Chronic Myeloid Leukemia (CML). Previously, we have published the synthesis of this natural alkaloid and three of its derivatives: Deoxyharringtonine (DHT), Deoxyhomoharringtonine (DHHT), and Bis(demethyl)-deoxyharringtonine (BDHT), and reported its refractory activity against the HL-60/RV+ cells over-expressing P-glycoprotein 1 (MDR1).</p><p><strong>Methods: </strong>In this study, we have explored the extent of this resistance by first expanding the panel of established cell lines and using a panel of 21 leukemia patient-derived primary cells.</p><p><strong>Results: </strong>Herein, we have reported consistent resistance to HTT of K562-derived cells and to mitoxantrone of MES-SA/MX2-derived cells; all of them have been found to overexpress MDR1, while we have found U87MG-ABCG2 and H69AR cells to be very sensitive to HTT. In contrast, DHT, DHHT, and BDHT seemingly overcame this resistance due to the changes made to the acyl chain of HTT, rendering the derivatives less susceptible to efflux. Surprisingly, the leukemia primary cells were very sensitive to HHT and its derivatives with low nanomolar potencies, followed by a new class of CDC7 kinase inhibitors, the anthracycline class of topoisomerase inhibitors, the DNA intercalator actinomycin-D, and the vinca alkaloid class of microtubule inhibitors. The mechanism of cell death induced by HTT and DHHT was found to be mediated via caspase 3 cleavage, leading to apoptosis.</p><p><strong>Conclusion: </strong>Taken together, our results confirm that HHT is a substrate for MDR1. It opens the door to a new opportunity to clinically evaluate HHT and its derivatives for the treatment of AML and other cancers.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496438","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":"Exploring You-gui Pill for the Treatment of Diabetic Erectile Dysfunction: Data Mining Analysis, Network Pharmacology and Experiments In Vitro.","authors":"Jiaqi Chen, Yanan Gao, Yanqiu Zhang, Yue Sun, Yue Jiang, Yong Yang, Mingxing Wang","doi":"10.2174/0113862073329189241014102457","DOIUrl":"https://doi.org/10.2174/0113862073329189241014102457","url":null,"abstract":"<p><strong>Introduction: </strong>The You-gui pill (YGP) is a classical compound used for treating antidiabetic erectile dysfunction (DMED). However, the specific active ingredients responsible for its effects on DMED and their mechanisms remain unclear.</p><p><strong>Methods: </strong>In this paper, we used data mining techniques to analyze high-frequency herbs and herb combinations used in Chinese medicine for the treatment of DMED based on existing literature. Using network pharmacology to study the active components and mechanism of action of YGP against DMED, molecular docking was used to analyze the interactions of the active components with major structural proteins, nonstructural proteins, and mutants. Also, the therapeutic effect of YGP on hyperglycemic modelling and its underlying mechanisms were experimentally validated in CCEC cells by analyzing the expression of its relevant target mRNAs.</p><p><strong>Results: </strong>Network pharmacological analysis identified the three core components of YGP as quercetin, kaempferol, and β-sitosterol, and constructed a PPI network map of common targets of YGP and DMED, which included HIF-1α, ALB, Bcl-2, INS, IL-1β, IL-6, TNF-α, CASP3, and TP53. Combined with molecular docking results, these targets had a strong binding affinity between them and the active ingredient compounds, with the highest affinity for HIF-1α and TNF-α. During the in vitro cellular assay validation, the HIF-1α, ALB, Bcl-2, TNF-α, and IL-6 mRNA in CCECs cells showed positive regulation after YGP intervention.</p><p><strong>Conclusion: </strong>The combination of \"data mining - network pharmacology - molecular docking - experimental validation\" provides a powerful methodological basis for the study of the main active components and mechanism of action of YGP against DMED, as well as the development and application of the drug.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496439","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":"To Reveal the Potential Mechanism of Quercetin against NSCLC Based on Network Pharmacology and Experimental Validation.","authors":"Baibai Ye, Ping Chen, Cheng Lin, Xinyu Liu, Jia Chen, Chenning Zhang, Linfu Li","doi":"10.2174/0113862073332751241008072644","DOIUrl":"https://doi.org/10.2174/0113862073332751241008072644","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to initially clarify the potential mechanism of quercetin in the treatment of non-small cell lung cancer (NSCLC) based on network pharmacology, molecular docking and in vitro experiments.</p><p><strong>Method: </strong>TCMSP, SwissTargetPrediction, TCMIP, STITCH, and ETCM databases were applied to obtain the targets of quercetin. NSCLC-related targets were retrieved from GeneCards, OMIM, PharmGKB, TTD, and NCBI databases. Their intersection targets were imported into the STRING database to construct a protein-protein interaction (PPI) network and core targets were identified through the Cytoscape 3.10.0 soft and the CytoHubba tool. Furthermore, Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersection targets. A compound-targetspathways network was subsequently constructed to screen for key targets and pathways. Molecular docking was performed with Discovery Studio software to verify the interactions between quercetin and core targets. In vitro validations were conducted employing CCK-8 assays, flow cytometry, and Western blotting (WB).</p><p><strong>Results: </strong>193 potential targets of quercetin for treating NSCLC were obtained. The top ten core targets identified within the PPI network included TP53, HSP90AA1, AKT1, JUN, SRC, EGFR, ACTB, TNF, MAPK1, and VEGFA. GO analysis yielded 2319 items, and KEGG analysis resulted in 211 enriched pathways. Molecular docking results demonstrated a high affinity of quercetin towards the core targets. Based on the compound-targets-pathways network and molecular docking, the PI3K/AKT/P53 pathway and its key-related proteins (PIK3R1, AKT1, and TP53) were selected for further validation. Quercetin(20 and 40 μg/mL) significantly decreased the viability of A549 NSCLC cells but not BEAS-2B normal cells via CCK-8 assays. Flow cytometry and WB analyses further corroborated that quercetin could promote apoptosis of A549 cells by downregulating and upregulating the expression of Bcl-2 and Bax (P<0.05), respectively. Notably, quercetin did not significantly alter the total protein levels of PI3K, AKT, and P53 but downregulated the phosphorylation levels of PI3K and AKT (P<0.05) and upregulated the phosphorylation level of P53 (P<0.05).</p><p><strong>Conclusion: </strong>Quercetin exhibits therapeutic potential in NSCLC by regulating the PI3K/AKT/P53 pathway to promote cell apoptosis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496440","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":"Steiner 3-Wiener Index of Zigzag Polyhex Nanotubes.","authors":"Medha Itagi Huilgol, P HShobha HShobha, H Jayakrishna Udupa, Ismail Naci Cangul","doi":"10.2174/0113862073329237240929214731","DOIUrl":"https://doi.org/10.2174/0113862073329237240929214731","url":null,"abstract":"<p><strong>Background: </strong>Let G be a connected graph and S be a k element subset of the vertex set V(G) of G. Steiner distance is a natural generalization of the usual graph distance. The Steiner-k distance dG(S) between the vertices of S is the minimum size among all connected subgraphs whose vertex set contains S. The generalized indices based on Steiner distances have several applications in the real world. It is a well-known fact that \"Steiner Problem\" is NP-complete and hence any parameter based on Steiner distance is also an NP problem.</p><p><strong>Objective: </strong>The objective of this work is to determine the Steiner 3-Wiener index for an important chemical structure called the zigzag polyhex nanotube.</p><p><strong>Methods: </strong>In this paper, we present an algorithm for computing the Steiner 3-Wiener index (SW3) for zigzag polyhex nanotubes. The developed algorithm addresses the complexities associated with exponential increments in the number of vertices as the nanotube's circumference or length expands. The obtained SW3 values for zigzag polyhex nanotubes can be used for Quantitative Structure-Activity Relationship (QSAR) and Quantitative Structure-Property Relationship (QSPR) analyses.</p><p><strong>Results: </strong>We have presented an algorithm and listed the numerical values of SW3 for various parameters of circumference and length of a zigzag polyhex nanotube to facilitate their utilization in QSAR/ QSPR analyses. We have obtained the time complexity for the algorithm, which shows that the SW3 values are computationally intensive. To explain this complex nature, we have used multiple linear regression to fit log SW3 values corresponding to log p and log q, the radius and length of a nanotube.</p><p><strong>Conclusion: </strong>The algorithm addresses the complexities associated with the exponential increase in vertices as the nanotube's circumference or length expands. Furthermore, we provide SW3 values for various parameter combinations up to circumference or length 17, and a general relation to determine the value of SW3, facilitating its utilization in real-world applications. These values serve as crucial descriptors for understanding the structural nuances of zigzag polyhex nanotubes, that find applications in material science, drug design, drug discovery, etc.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459770","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":"Wuzi-Yanzong-Wan Prevents the Defect of Cell-Cell Junctions between Sertoli-Germ Cells by Up-Regulating the Expression of TAp73.","authors":"Li Li, Min Pan, Ziao Liu, Hongsu Zhao, Fengqing Xu, Xiaohui Tong, Yajuan Wang, Bin Chen, Lihua Yu, Tongsheng Wang","doi":"10.2174/0113862073328011241004110538","DOIUrl":"https://doi.org/10.2174/0113862073328011241004110538","url":null,"abstract":"<p><strong>Background: </strong>The TAp73 gene is an anti-cancer gene that also affects the junction between Sertoli and germ cells. Inhibition of this gene causes infertility in male mice. Our previous research proved that Wuzi-Yanzong-Wan (WZYZW) can protect spermatogenesis and maturation by preventing TAp73 inhibition.</p><p><strong>Objective: </strong>This study aimed to investigate the effect of drug-containing serum of WZYZW on the defect of cell-cell junctions in the Sertoli-germ cells co-culture system in vitro.</p><p><strong>Methods: </strong>LC-HRMS was used to analyze the content of active ingredients in WZYZWmedicated serum. Then, primary extraction and co-culture of germ cells and Sertoli cells were carried out. Co-cultured cells were added with PFT-α to induce the TAp73 inhibition model, with WZYZW-medicated serum at 2.5%, 5%, and 10% treated in parallel. Sloughing of germ cells from Sertoli cells was calculated. Transmission electron microscopy (TEM), Immunofluorescence, qRT-PCR, and western blot methods were employed.</p><p><strong>Results: </strong>The drug-containing serum of WZYZW contained schisandrin, hyperoside, geniposidic acid, ellagic acid, and quercetin. Using TEM assay, we observed restoration of the desmosomelike (Des), tight junctions (TJ), and basal ectoplasmic specialization (ES) structure following WZYZW treatment. WZYZW caused inhibition of peptidase and protease inhibitors (tissue inhibitor of metalloproteinase-1 (TIMP1), Serpina3n) by immunofluorescence analysis. Western blot and qRT-PCR analysis revealed that WZYZW was able to ameliorate the expressions of peptidase and protease inhibitors and cell adhesion factors, such as TAp73, TIMP1, Serpina3n, Desmocollin-3, N-cadherin, and Nectin-2.</p><p><strong>Conclusion: </strong>WZYZW-medicated serum could prevent the defect of cell-cell junctions between Sertoli-germ cells co-culture system in vitro by up-regulating the expression of TAp73.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459783","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":"Regulation of Curcumin on Follicle Initiation Rate in Diminished Ovarian Reserve.","authors":"Wanjing Li, Jinbang Xu, Jingyi Wang, Junxin Zhang, Disi Deng","doi":"10.2174/0113862073327087240926065629","DOIUrl":"https://doi.org/10.2174/0113862073327087240926065629","url":null,"abstract":"<p><strong>Aim: </strong>To study the mechanism by which curcumin regulates ovarian primordial follicle initiation in rats with triptolide-induced diminished ovarian reserve (DOR).</p><p><strong>Methods: </strong>An in vitro gelatin sponge culture was performed on 3-day-old rat ovaries. After the establishment of the DOR model with triptolide, curcumin was administered for 3 days. Histological analysis and follicle counts were performed using H&E staining. ELISA detection of ovarian hormones in the culture medium (E2, FSH and LH), western blotting and Q-PCR for protein and mRNA expression (LTCONS-00011173, TGF-β1, Smad1, AMH, PTEN and GDF-9).</p><p><strong>Results: </strong>Ovarian primordial and growing follicles increased significantly after curcumin intervention (p < 0.05), FSH/LH and E2 levels were increased significantly (p < 0.05). Curcumin also significantly decreased the expression of LTCONS-00011173. Meanwhile, curcumin increased the expression of TGF-β, AMH, and GDF-9 (p < 0.05). In addition, curcumin increased Smad1 gene expression and protein phosphorylation in the ovary on the one hand (p < 0.05), but inhibited Smad1 and p-Smad1 protein expression on the other hand (p < 0.05). Moreover, curcumin decreased PTEN protein and mRNA expression (p < 0.05).</p><p><strong>Conclusion: </strong>Curcumin activates primordial follicles in DOR model rats through TGF-β1 and downstream AMH signaling pathways and may limit follicle exhaustion through LncRNA.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459769","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":"Effective Components and Molecular Mechanism of Biejiaruangan Capsule Against Liver Fibrosis: High-resolution Mass Spectrometry, Network Pharmacological Analysis and Experimental Verification.","authors":"Kefeng Cao, Hui Jiang, Lili Zhang, Chang Fan, Zhigang Feng, Biao Li, Laicheng Song, Qun Zhang","doi":"10.2174/0113862073338867240930031800","DOIUrl":"https://doi.org/10.2174/0113862073338867240930031800","url":null,"abstract":"<p><strong>Background: </strong>Biejiaruangan capsule (BJRGC) is a commonly used traditional Chinese medicine preparation for treating oftreating liver fibrosis (LF), but its specific molecular mechanism is unclear. This study used mass spectrometry, network pharmacology and experimental verification to explore the mechanism of BJRGC against LF.</p><p><strong>Methods: </strong>Ultrahigh-performance liquid chromatography-quadrupole-exactive-orbitrap-mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS) and network pharmacology were employed to identify and screen the potential components, targets, and signaling pathways of BJRGC against LF. The interaction between the active ingredients and targets was validated using molecular docking. Finally, 5-ethynyl-2'-deoxyuridine (EDU) staining, western blotting (WB), and flow cytometry (FCM) were utilized to further verify the mechanism of BJRGC against LF.</p><p><strong>Results: </strong>A total of 9 prototype components of BJRGC were identified in serum, most derived from iridoid glycosides and triterpenes in Gardenia jasminoides Ellis and Artemisia scoparia Waldst.et Kit. Network pharmacology predicts that medicine prototype components in serum mostly influence targets such as CDK2, CDK6, and PIK3CG, with the key route being the PI3K/AKT signaling pathway. Molecular docking showed that the major components have good binding properties with key target proteins. The experimental results showed that BJRGC could inhibit the proliferation of HSCs, induce cell cycle arrest and reduce the protein expression of CDK2, CDK6 and PIK3CG.</p><p><strong>Conclusions: </strong>BJRGC can inhibit the proliferation of HSCs by targeting the protein expression of CDK2, CDK6, and PIK3CG in the PI3K/AKT signaling pathway through its prototype components, such as hyperoside, tumulosic acid, and hederagenin, thereby alleviating LF disease.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459767","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":"KLF15 Transcription Activated Tachykinin Precursor 1 to Induce Perineural Invasion in Head and Neck Squamous Cell Carcinoma.","authors":"Yupeng Shen, Yong Shi, Xin Liu, Ming Zhang, Liang Zhou, Chengzhi Xu","doi":"10.2174/0113862073331908241002044719","DOIUrl":"https://doi.org/10.2174/0113862073331908241002044719","url":null,"abstract":"<p><strong>Objective: </strong>In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC).</p><p><strong>Methods: </strong>The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRTPCR.</p><p><strong>Results: </strong>A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC.</p><p><strong>Conclusion: </strong>This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459768","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":"Discovering the Untouched Perspective of Endangered North American Herb Actaea racemosa.","authors":"Genevive Kharumnuid, Rashmi Saxena Pal, Yogendra Pal, Motamarri Naga Lalitha Chaitanya, Preeti Srivastava","doi":"10.2174/0113862073309185240923053809","DOIUrl":"https://doi.org/10.2174/0113862073309185240923053809","url":null,"abstract":"<p><p>Actaea racemosa (AR), sometimes also known as black cohosh, is a perennial herb that grows in the Ranunculaceae family that effloresces in the middle of summer. This herb is currently present throughout south and west North America despite being endangered in the eastern section of the continent. Certain information about the photochemistry and biological potential of this herb is available. In accordance with the scant available ethno-medical reports, this herb possesses antioxidant, antidiabetic, anti-inflammatory, antiosteoporosis, and anticancer properties. As per the available literature, caffeic acid, isoferulic acid, actein, 23-epi-26 deoxycatein, cimicifugoside, and ferukinolic acid are the key components found in different parts of AR. To date, no thorough research or systematic review has been done to highlight the traditional, biological, and phytochemical benefits of this herb. Consequently, further research is needed to gain a deeper understanding of this therapeutic herb, particularly about its separation and pharmacological screening of its insulating portion for a range of biological functions. The goal of this review was to compile the most recent data on the phytochemical presence of AR. in relation to its ethnomedical applications, methods of extraction, pharmacological applications, and future potential.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459766","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":"Astaxanthin Alleviates Chronic Prostatitis via the ERK1/2 Signaling Pathway: Evidence from Network Pharmacology and Experimental Validation.","authors":"Yifu Liu, Liang Huang, Zhicheng Zhang, Qiqi Zhu, Ping Xi, Ting Sun, Binbin Gong","doi":"10.2174/0113862073331381240923080152","DOIUrl":"https://doi.org/10.2174/0113862073331381240923080152","url":null,"abstract":"<p><strong>Background: </strong>Astaxanthin (AST) has been widely recognized for its therapeutic potential in chronic inflammatory ailments. This study investigates the therapeutic efficacy and underlying mechanisms of AST in the management of chronic prostatitis (CP).</p><p><strong>Methods: </strong>Male Sprague-Dawley (SD) rats were randomly divided into control, complete Freund's adjuvant (CFA), and CFA + AST groups. CFA was used to induce the CP model, and saline was used for the control group. Inflammation of the prostate was detected 28 days after oral administration of AST. qRT-PCR and ELISA were used to detect pro-inflammatory factors in RWPE-1 and WPMY-1 cells. Potential targets of AST for CP were explored by network pharmacology, and related proteins were detected by Western blotting.</p><p><strong>Results: </strong>Oral administration of AST alleviated the increase in prostate stroma and reduced inflammatory cell infiltration in CP rats. The IC50 of AST-treated RWPE-1 and WPMY-1 cells for 48 h were 171 and 212.1 μM, respectively. AST pretreatment reduced IL-6 and IL-8 expression in these cells. PPI network, GO, and KEGG enrichment analyses suggested that the antiinflammatory effect of AST was associated with the ERK1/2 pathway. Western blotting showed that AST inhibited ERK1/2 phosphorylation. In addition, AST and ERK1/2 pathway inhibitors (U0126) synergistically inhibited LPS-induced inflammation in prostate cells.</p><p><strong>Conclusion: </strong>Our study identified the potential of AST in the treatment of CP. However, subsequent randomized controlled trials are needed to validate its clinical efficacy.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459765","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}