Current pharmaceutical biotechnology最新文献

{"title":"TP508 Promotes Bone Regeneration on Distraction Osteogenesis <i>via</i> the Activation of Wnt/β-catenin Signaling Pathway.","authors":"Kehan Li, Linan Liu, Jingyi Zhang, Chenyu Liao, Jian Hu, Jian Song","doi":"10.2174/0113892010289575240306033011","DOIUrl":"10.2174/0113892010289575240306033011","url":null,"abstract":"<p><strong>Introduction: </strong>TP508 is a thrombin peptide that participates in the inflammatory response and wound healing. Its role in the molecular mechanism of distraction osteogenesis remains unclear. This study established a tibia distraction osteogenesis (DO) model in rats and investigated the role and mechanism of TP508 in bone regeneration during DO.</p><p><strong>Method: </strong>Micro-computed tomography (Micro-CT) and hematoxylin-eosin (HE) staining were used to track osteogenesis. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to measure the expression of osteoblast-related factors, Wnt/β- catenin signaling-related proteins and genes. Immunohistochemistry was used to measure the expression of β-catenin in the cytoplasm and nucleus.</p><p><strong>Results: </strong>TP508 accelerated bone regeneration increased the expression of the osteoblast-related factors Alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). After the Wnt signaling was inhibited by LGK974, the expression of osteoblastrelated factors was downregulated, leading to a decrease in bone regeneration ability. More importantly, TP508 upregulated β-catenin and its target CYCLIN-D1 and could reverse the decreased osteogenic ability caused by LGK974.</p><p><strong>Conclusion: </strong>In conclusion, TP508 promotes bone regeneration in DO by activating the Wnt/β- catenin signaling pathway.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"402-410"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101238","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":"Expression of LASS2 Can be Regulated by Dihydroartemisinin to Regulate Cisplatin Chemosensitivity in Bladder Cancer Cells.","authors":"Xuhua Qiao, Rongbo Xue, Shijie Li, Jun Li, Chundong Ji","doi":"10.2174/0113892010305651240514100129","DOIUrl":"10.2174/0113892010305651240514100129","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to investigate the potential of dihydroartemisinin to augment the efficacy of cisplatin chemotherapy through the modulation of LASS2 expression.</p><p><strong>Methods: </strong>TCMSP, CTR-DB, TCGA-BLC, and other databases were used to analyze the possibility of LASS2 as the target gene of dihydroartemisinin. Cell experiments revealed the synergistic effect of DDP and DHA. Animal experiments showed that DHA inhibited the growth of DDP-treated mice. In addition, WB, real-time PCR, and immunohistochemical analysis showed that DHA enhanced LASS2 (CERS2) expression in bladder cancer cells and DDP-treated mice.</p><p><strong>Results: </strong>LASS2 is associated with cisplatin chemosensitivity.LASS2 expression levels are different between BLC tissues and normal tissues. COX analysis showed that patients with high LASS2 expression had a higher cumulative overall survival rate than those with low LASS2 expression. The Sankey plot showed that LASS2 expression is lower in BLC tissues with more advanced stage and distant metastasis. The docking score of DHA and LASS2 reached the maximum value of -5.5259, indicating that DHA had a strong binding affinity with LASS2 targets. CCK8 assay showed that the most effective concentration ratio of DHA to DDP was 2.5 μg/ml + 10μg/ml. <i>In vivo</i> experiments showed that DHA inhibited tumor growth in cisplatin-treated mice. In addition, WB, RT-qPCR, and immunohistochemical analysis showed that DHA was able to enhance LASS2 expression in BLC cells and DDP-treated mice.</p><p><strong>Conclusion: </strong>The upregulation of LASS2 (CERS2) expression in bladder cancer cells by DHA has been found to enhance cisplatin chemosensitivity.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"525-538"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956478","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":"Gossypetin Alleviates DSS-induced Colitis by Regulating COX2 and ROS-JNK Signaling.","authors":"Hyeonjin Kim, Eungyung Kim, Lei Ma, ChaeYeon Kim, Kanghyun Park, Zhibin Liu, Ke Huang, Dong Joon Kim, Zae Young Ryoo, Jun Koo Yi, Yonghun Sung, Soyoung Jang, Myoung Ok Kim","doi":"10.2174/0113892010331882240901095733","DOIUrl":"10.2174/0113892010331882240901095733","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory Bowel Disease (IBD) represents a chronic and recurrent inflammatory condition affecting the gastrointestinal tract, with a rising global incidence. Current treatment approaches include surgery and drugs. However, surgeries are invasive procedures, while drug treatments often present with various side effects. Gossypetin, a flavonoid found abundantly in plants such as hibiscus, exhibits anti-oxidant and anti-cancer properties. However, its potential impact on IBD remains unexplored.</p><p><strong>Objective: </strong>This study aimed to investigate the therapeutic potential of gossypetin on colitis.</p><p><strong>Methods: </strong>We employed the DSS-induced colitis model to evaluate the therapeutic potential of gossypetin on colitis. The efficacy of gossypetin was assessed within this model using the Disease Activity Index (DAI) score and histological analysis. Additionally, we utilized qRT-PCR to measure the levels of inflammatory cytokines and Superoxide Dismutase (SOD). Immunohistochemistry confirmed the expression of tight junction markers, COX-2, and phosphorylated JNK protein, normally associated with disease progression. Furthermore, Western blot analysis was conducted to examine the SOD levels and anti-apoptotic effects of gossypetin.</p><p><strong>Results: </strong>In DSS-induced colitis mice, gossypetin treatment ameliorated weight loss and reduced colon length caused by DSS treatment. Additionally, gossypetin-treated groups exhibited DAI scores and reduced histological damage. Moreover, gossypetin treatment increased tight junction expression, decreased inflammatory responses, reduced ROS levels, attenuated JNK signaling, and decreased apoptosis.</p><p><strong>Conclusion: </strong>Gossypetin shows therapeutic potential for mitigating the symptoms and progression of colitis by targeting ROS-JNK signaling involved in inflammation and tissue damage. This highlights the potential of natural compounds such as gossypetin for targeted therapies with reduced side effects and improved efficacy.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"769-777"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726843","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":"<i>Guettarda viburnoides</i> Cham. & Schltdl.: Neuroprotective Activities in Mice, Molecular Docking and Microchemical and Morphoanatomical Characteristics of Leaves and Stems.","authors":"Pedro Cruz de Oliveira Junior, Eliana Janet Sanjinez-Argandona, Janaine Alberto Marangoni Faoro, Rosilda Mara Mussury Franco Silva, Elisabete Castelon Konkiewitz, Edward Benjamin Ziff, Marcia Regina Pereira Cabral, Maria Helena Sarragiotto, Gisele de Freitas Gauze, Andrew Matheus Frederico Rozada, Luciane Mendes Monteiro, Jane Manfron, Anelise Samara Nazari Formagio","doi":"10.2174/0113892010318163240822063318","DOIUrl":"10.2174/0113892010318163240822063318","url":null,"abstract":"<p><strong>Background: </strong><i>Guettarda viburnoides</i> Cham. & Schltdl., \"veludinho do campo\", is used in the Brazilian Amazon for its effects on the central nervous system (CNS) as a \"brain tonic\"; however, scientific evidence is needed to elucidate its ethnobotanical uses.</p><p><strong>Objectives: </strong>This study evaluated the neurobehavioural effects of an ethanolic extract of <i>G. viburnoides</i> (EEGV). Molecular docking, microchemical and morphoanatomical features of the species were investigated.</p><p><strong>Methods: </strong>EEGV was investigated by UHPLC‒MS/MS and dereplication and molecular network were investigated using platforms available for natural product chemistry. For the <i>in vivo</i> assay, EEGV was administered to mice orally (3, 30 or 100 mg/kg). The effect of EEGV on spatial memory was measured using the Morris water maze test in mice with scopolamine-induced amnesia. The depression- and anxiety-like effects were assessed by forced swimming, tail suspension, marble burying and elevated plus maze tests. The AChE inhibition was evaluated in the brains of treated mice and molecular docking simulations were carried out with the main constituents. The leaves and stems of <i>G. viburnoides</i> were analysed via optical microscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy.</p><p><strong>Results: </strong>Secoxyloganin, grandifloroside, hyperin/or isoquercitrin, uncaric acid and ursolic acid were identified by UHPLC‒MS/MS. Molecular networking by three flavonoids, three triterpenes, two coumarins, two iridoids, and one phenolic acid. EEGV reversed these scopolamineinduced effects. In the forced swim and tail suspension test, EEGV (30 and 100 mg/kg) significantly reduced the immobility time. EEGV significantly reduced the number of buried marbles, while in the elevated plus maze test, no changes were observed compared to the Sco group. AChE activity was altered in the hippocampus. Studies of the molecular coupling of iridoid glycosides (grandifloroside and secoxyloganin) and flavonoid hyperin with AChE revealed significant interactions, corroborating the activity indicated by the inhibition assay.</p><p><strong>Conclusion: </strong>These results might be in accordance with medicinal use for neuroprotetor effects and important microchemical and micromorphological data that support the identification and quality control of <i>G. viburnoides</i>.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"836-853"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139471","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":"DHA and Cancer: The Uncharted Territory of Nutritional Oncology.","authors":"Devank Shekho, Abhishek Chauhan, Ritika Mishra, Ankit Awasthi","doi":"10.2174/0113892010305256240422110943","DOIUrl":"10.2174/0113892010305256240422110943","url":null,"abstract":"","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"313-315"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847211","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":"<i>In vitro</i> Antileishmanial Activity and <i>In silico</i> Molecular Modeling Studies of Novel Analogs of Dermaseptins S4 and B2.","authors":"Houda Haddad, Klinger Antonio da Franca Rodrigues, Houcemeddine Othman, Leiz Maria Costa Veras, Raiza Raianne Luz Rodrigues, Ines Ouahchi, Bouraoui Ouni, Amira Zaϊri","doi":"10.2174/0113892010296038240427050421","DOIUrl":"10.2174/0113892010296038240427050421","url":null,"abstract":"<p><strong>Background: </strong>Leishmaniasis is responsible for approximately 65,000 annual deaths. Various Leishmania species are the predominant cause of visceral, cutaneous, or mucocutaneous leishmaniasis, affecting millions worldwide. The lack of a vaccine, emergence of resistance, and undesirable side effects caused by antileishmanial medications have prompted researchers to look for novel therapeutic approaches to treat this disease. Antimicrobial peptides (AMPs) offer an alternative for promoting the discovery of new drugs.</p><p><strong>Methods: </strong>In this study, we detail the synthesis process and investigate the antileishmanial activity against <i>Leishmania (Viannia) braziliensis</i> for peptides belonging to the dermaseptin (DS) family and their synthetic analogs. The MTT assay was performed to investigate the cytotoxicity of these peptides on the murine macrophage cell line RAW 264.7. Subsequently, we performed molecular modeling analysis to explore the structure-function correlation of the derivatives interacting with the parasitic membrane.</p><p><strong>Results: </strong>All examined derivatives displayed concentration-dependent antileishmanial effect at low concentrations. Their effectiveness varied according to the peptide's proprieties. Notably, peptides with higher levels of charge demonstrated the most pronounced activities. Cytotoxicity assays showed that all the tested peptides were not cytotoxic compared to the tested conventional drug. The structure-function relationships demonstrated that the charged N-terminus could be responsible for the antileishmanial effect observed on promastigotes.</p><p><strong>Conclusion: </strong>Collectively, these results propose that dermaseptins (DS) might offer potential as promising candidates for the development of effective antileishmanial therapies.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"276-288"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281697","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":"Recent Developments in Nanotechnology and Immunotherapy for the Diagnosis and Treatment of Pancreatic Cancer.","authors":"Komal Sindhi, Abhishek Kanugo","doi":"10.2174/0113892010284407240212110745","DOIUrl":"10.2174/0113892010284407240212110745","url":null,"abstract":"<p><p>Pancreatic cancer kills millions of people worldwide each year and is one of the most prevalent causes of mortality that requires prompt therapy. A large number of people suffering from pancreatic cancer are detected at an advanced stage, with incurable and drug-resistant tumor, hence the overall survival rate of pancreatic cancer is less. The advance phase of this cancer is generated because of expression of the cancer-causing gene, inactivation of the tumorsuppressing gene, and deregulation of molecules in different cellular signalling pathways. The prompt diagnosis through the biomarkers significantly evades the progress and accelerates the survival rates. The overexpression of Mesothelin, Urokinase plasminogen activator, IGFR, Epidermal growth factor receptor, Plectin-1, Mucin-1 and Zinc transporter 4 were recognized in the diagnosis of pancreatic cancer. Nanotechnology has led to the development of nanocarriersbased formulations (lipid, polymer, inorganic, carbon based and advanced nanocarriers) which overcome the hurdles of conventional therapy, chemotherapy and radiotherapy which causes toxicity to adjacent healthy tissues. The biocompatibility, toxicity and large-scale manufacturing are the hurdles associated with the nanocarriers-based approaches. Currently, Immunotherapybased techniques emerged as an efficient therapeutic alternative for the prevention of cancer. Immunological checkpoint targeting techniques have demonstrated significant efficacy in human cancers. Recent advancements in checkpoint inhibitors, adoptive T cell therapies, and cancer vaccines have shown potential in overcoming the immune evasion mechanisms of pancreatic cancer cells. Combining these immunotherapeutic approaches with nanocarriers holds great promise in enhancing the antitumor response and improving patient survival.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"143-168"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982543","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":"cRGD-platelet@MnO/MSN@PPARα/LXRα Nanoparticles Improve Atherosclerosis in Rats by Inhibiting Inflammation and Reducing Blood Lipid.","authors":"Zheng Lv, Yupeng Zhang, Mengke Lu, Ziyi Wang, Xiaoyue Nong, Guoliang Wen, Wei Zhang","doi":"10.2174/0113892010314993240819065655","DOIUrl":"10.2174/0113892010314993240819065655","url":null,"abstract":"<p><strong>Objective: </strong>Atherosclerosis (AS) is an inflammatory disease of arterial intima driven by lipids. Liver X receptor alpha (LXRα) and peroxisome proliferator-activated receptor alpha (PPARα) agonists are limited in the treatment of AS due to their off-target effects and serious side effects. Therefore, this study was designed to construct a novel nanoparticle (NP) and evaluate its mechanism of action on inflammation inhibition and lipid reduction in AS.</p><p><strong>Methods: </strong>We synthesized cRGD-platelet@MnO/MSN@PPARα/LXRα NPs (cRGD-platelet- NPs) and confirmed their size, safety, and targeting ability through various tests, including dynamic light scattering and immunofluorescence. In vivo and in vitro experiments assessed cell proliferation, apoptosis, inflammation, and plaque formation. Finally, the NF-κB signaling pathway expression in rat aorta was determined using a western blot.</p><p><strong>Results: </strong>The synthesis of cRGD-platelet-NPs was successful; the particle size was approximately 150 nm, and the PDI was below 0.3. They could be successfully absorbed by cells, exhibiting high safety in vivo and in vitro. The cRGD-platelet-NPs successfully reduced plaque formation, improved lipid profiles by lowering LDL-cholesterol, total cholesterol, and triglycerides, and raised HDL-cholesterol levels. Additionally, they decreased inflammatory markers in the serum and aortic tissue, suggesting reduced inflammation. Immunohistochemistry and western blot analyses indicated that these NPs could not only promote M2 macrophage polarization but also suppress the NF-κB signaling pathway.</p><p><strong>Conclusion: </strong>The newly developed cRGD-platelet-NPs with high safety are a promising approach to AS treatment, which can regulate ABCA1, reduce the formation of AS plaques, and enhance cholesterol efflux. The mechanism may involve the suppression of the NF-κB signaling pathway.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"740-753"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119205","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 Comprehensive Pan-cancer Analysis Identified that TRIB3 was Associated with Immune Cell Infiltration and Poor Prognosis.","authors":"Ke-Xun Yu, Wei-Jie Yuan, Jing-Li, Hui-Zhen Wang, Yong-Xiang Li","doi":"10.2174/0113892010308103240830063504","DOIUrl":"10.2174/0113892010308103240830063504","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have demonstrated that TRIB3 plays a carcinogenic role in tumor progression. However, the exploration of TRIB3 at the pan-cancer level has not been reported.</p><p><strong>Aims: </strong>This study aimed to conduct a comprehensive pan-cancer analysis of TRIB3.</p><p><strong>Objectives: </strong>We explored the expression pattern and functional mechanism of TRIB3 on the basis of multiple databases.</p><p><strong>Methods: </strong>We first explored the expression level of TRIB3 in the TCGA database. Then, the receiver operation characteristic curve (ROC), Kaplan-Meier plotter, and Cox regression were used to estimate the diagnostic and prognostic value of TRIB3, respectively. We also explored the relationship between TRIB3 and the infiltration of tumor immune cells, as well as the expression of immune checkpoint molecules. Gene enrichment and protein interaction network analysis were carried out to identify possible carcinogenic molecular mechanisms and functional pathways. Finally, we compared the non-promoter region methylation of TRIB3 in normal and tumor tissues and explored potential systems with unique functions in TRIB3-mediated tumorigenesis.</p><p><strong>Results: </strong>The expression level of TRIB3 was elevated in multiple tumor types, and the high expression of TRIB3 was associated with poor prognosis. TRIB3 had a higher frequency of genetic changes in several tumors and showed varying trends in TRIB3 methylation levels. Additionally, high expression of TRIB3 was also associated with infiltration of cancer-related fibroblasts and different types of immune cells and was positively correlated with the expression of immune checkpoint molecules. Furthermore, gene enrichment analysis suggested that TRIB3 may play a role in the malignant progression of cancer by participating in protein post-translational modifications and activating transcription initiation factors.</p><p><strong>Conclusion: </strong>Our pan-cancer analysis provided the potential carcinogenic role of TRIB3 in tumors and verified a promising target for clinical immune treatment.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"878-901"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281629","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":"Integrated Serum Pharmacochemistry, Network Pharmacology, and Molecular Docking to Study the Mechanism of Rhubarb against Atherosclerosis.","authors":"Zhi-Yan Cai, Shu-Jiao Li, Yu-Qing Wang","doi":"10.2174/0113892010296117240531071301","DOIUrl":"10.2174/0113892010296117240531071301","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS) is a chronic inflammatory disease characterized by the accumulation of lipids, the formation of lesion plaques, and the narrowing of arterial lumens. Rhubarb has significant effects against AS, but there is a lack of analysis and exploration of the mechanism of action of the transitional components in serum containing rhubarb.</p><p><strong>Objective: </strong>This work aims to combine serum pharmacochemistry, network pharmacology, and molecular docking to explore active ingredients and mechanism of rhubarb against AS.</p><p><strong>Method: </strong>Firstly, the components of rhubarb in blood samples were identified using HPLC-QTOF/ MS. The ingredients-targets-disease interaction network of rhubarb was constructed through network pharmacology. Then, molecular docking between the ingredients and the core targets was carried out using the Autodock Vina software.</p><p><strong>Results: </strong>Eleven active ingredients and five metabolites were preliminarily identified. The network pharmacology results showed that chrysophanol, resveratrol, and emodin might have potential pharmacological effects on AS. The PPI network showed that the key proteins were PTGS2, ESR1, PTGS1, and ELANE. GO analysis revealed that genes were mainly enriched in the inflammatory response and response to exogenous stimuli. Moreover, these genes were related to IL-17 signaling pathways, lipid and atherosclerosis, and other pathways. Molecular docking analyses showed that chrysophanol and emodin have strong binding affinities with the target proteins PTGS2 and PTGS1.</p><p><strong>Conclusion: </strong>A comprehensive strategy combining serum pharmacochemistry with network pharmacology and molecular docking was employed to investigate the active ingredients and the mechanism of rhubarb in treating AS, which provided a basis for studying the pharmacological effects and action mechanisms of rhubarb.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"564-575"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283234","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}