Combinatorial chemistry & high throughput screening最新文献

{"title":"Uncovering ShuangZi Powder's Anti-Ovarian Cancer Mechanism: A Systems Biology and Experimental Approach.","authors":"Wangang Gong, Yao Hong, Wumin Dai, Yingli Zhang","doi":"10.2174/0113862073394765250828100829","DOIUrl":"https://doi.org/10.2174/0113862073394765250828100829","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the anti-ovarian cancer (OC) effects of Shuangzi Powder (SZP) and its regulatory impact on the tumor microenvironment.</p><p><strong>Method: </strong>This study employed systems biology approaches, integrating molecular docking and experimental validation, to explore the pharmacological mechanisms of SZP in OC treatment. To identify potential bioactive compounds and target genes of SZP, network pharmacology, protein- protein interaction network analysis, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted.</p><p><strong>Results: </strong>Among the 11 bioactive ingredients identified in SZP, 1,767 potential therapeutic targets were predicted, while 2,637 differentially expressed genes were found to be associated with OC. KEGG pathway analysis revealed significant enrichment in pathways related to cancer, apoptosis, the PI3K-Akt signaling pathway, and the PD-L1/PD-1 checkpoint pathway. Treatment of A2780 cells with β,β-Dimethylacrylshikonin (DMAS) inhibited cell viability, migration, and invasion. Moreover, DMAS downregulated the expression of cell cycle- and apoptosis-related genes (CCNB1, CHEK1, CCNE1, and PARP1) and upregulated the immune checkpoint gene PD-L1. These findings indicate that multiple components, targets, and pathways are involved in OC treatment by SZP.</p><p><strong>Conclusion: </strong>DMAS, one of the bioactive ingredients of SZP, was predicted and preliminarily validated to exert inhibitory effects on OC cells, mainly through the regulation of the cell cycle, apoptosis, and immune response, as demonstrated by molecular docking and experimental analyses.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205868","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":"Chemical Diversity of Carotenoids Derived from Aquatic Animals and their Therapeutic, Biomedical, and Natural Colorant Applications.","authors":"Aminur Rahman, Pranab Borah, Saddam Hussain, Arlin Sen, Raju Bharalee, Mayuri Chabukdhara, Hrishikesh Upadhyaya, Akalesh Kumar Verma","doi":"10.2174/0113862073377688250903053348","DOIUrl":"https://doi.org/10.2174/0113862073377688250903053348","url":null,"abstract":"<p><p>Carotenoids, prevalent in a diverse range of aquatic animals, perform critical and multifaceted roles essential for marine and freshwater ecosystems. This review examines the distribution, biological functions, and potential biomedical applications of carotenoids sourced from various aquatic animals. Carotenoids are acquired through food consumption or metabolic pathways, playing vital roles such as photoprotection, antioxidant defense, and nutritional enhancement, particularly provitamin A. Marine sponges and cnidarians display a diverse spectrum of carotenoids, crucial for symbiosis and photoprotection. Molluscs and crustaceans exhibit varied carotenoid profiles corresponding to their trophic strategies, whereas fish and echinoderms utilize carotenoids in reproductive and developmental processes. In biomedical contexts, carotenoids act as potential anti-cancer agents and antioxidants. Lycopene, β-carotene, and astaxanthin demonstrate anti-proliferative and antioxidant effects, pivotal in cancer prevention and therapeutic interventions. Their applications extend to biomedical technologies like Raman spectroscopy and drug delivery systems, underscoring their diagnostic and therapeutic potential. Carotenoids, as powerful antioxidants, neutralize free radicals and diminish oxidative stress, which is linked to chronic diseases like cardiovascular diseases, neurodegenerative disorders, and cancer. Some carotenoids, such as beta-carotene, are precursors to vitamin A, vital for vision, immune response, and cell communication. Furthermore, carotenoids have anti-inflammatory properties that modulate inflammatory pathways and provide therapeutic potential in diseases like inflammatory bowel disease and arthritis, which are marked by chronic inflammation. Furthermore, carotenoids provide photoprotection, safeguarding the skin and other tissues from damage caused by ultraviolet radiation. This paper highlights the integral role of carotenoids in biomedical advancements, emphasizing their significance in human health research.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205844","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":"Shen-Ling-Bai-Zhu-San Mitigates Ulcerative Colitis by Enhancing Intestinal Barrier Integrity via the AhR-CYP1A1-NF-κB Signal Pathway.","authors":"Lan Ming, Jie Chen, Jing Ma, ShiQi Guo, Ke Xu, JiaMin Ji, ZhiRong Zhao, ShuGuang Xu, Qian Huang","doi":"10.2174/0113862073425771250828112001","DOIUrl":"https://doi.org/10.2174/0113862073425771250828112001","url":null,"abstract":"<p><strong>Introduction: </strong>Ulcerative Colitis (UC) represents a persistent inflammatory disorder of the colon, typically characterized by abdominal discomfort, diarrhea, and blood stools. Shen- Ling-Bai-Zhu-San (SLBZS), a traditional Chinese herbal formula, has shown clinical efficacy in alleviating symptoms such as abdominal bloating, frequent loose stools, and diarrhea. Nonetheless, the precise molecular mechanisms underlying its therapeutic effects remain largely unclear.</p><p><strong>Methods: </strong>UPLC-QE-MS combined with network pharmacology was employed to identify bioactive compounds and potential targets of SLBZS. A Dextran Sulfate Sodium (DSS)-induced colitis mouse model was used to evaluate its effects by monitoring changes in body weight, colon length, Disease Activity Index (DAI), inflammatory cytokines, oxidative stress markers, tight junction proteins, immunofluorescence, and histopathology. Molecular docking was used to predict the interaction of active compounds with UC-related targets, and Western blot analysis was performed to validate signaling pathways.</p><p><strong>Results: </strong>SLBZS markedly improved DSS-induced colitis by restoring body weight, colon length, DAI, and histology. It suppressed pro-inflammatory cytokines and oxidative markers while enhancing antioxidant defenses. Expression of Occludin and Claudin-1 was recovered. UPLCMS/ MS identified 458 constituents, and network pharmacology revealed 98 potential targets enriched in NF-κB, TNF, and HIF-1 pathways. Validation experiments demonstrated the upregulation of AhR and CYP1A1 with concomitant downregulation of NLRP3 and IL-6. Molecular docking confirmed high-affinity interactions between key compounds and UC-related targets.</p><p><strong>Discussion: </strong>These results indicate that SLBZS exerts its effects through anti-inflammatory and antioxidant mechanisms while strengthening the intestinal barrier, reflecting its multi-target therapeutic potential.</p><p><strong>Conclusions: </strong>SLBZS alleviates UC by regulating the AhR-CYP1A1-NF-κB axis, suppressing inflammation, and maintaining mucosal barrier function.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198504","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":"Zuojinwan Antagonizes Drug Resistance Transmission of Gastric Cancer Induced by Hypoxia Through Exosomal Mir-30a Mediated Hedgehog/ PD-L1 Signalling.","authors":"Zhenzhen Wei, Zan Li, Bowang Li, Zhen Chen, Yuli Zhang, Hua Sui, Qingfeng Tang","doi":"10.2174/0113862073367894250925093658","DOIUrl":"https://doi.org/10.2174/0113862073367894250925093658","url":null,"abstract":"<p><strong>Introduction: </strong>Our previous studies have demonstrated that the traditional Chinese medicine (TCM) formula, Zuo Jin Wan (ZJW), could significantly enhance the sensitivity of chemoresistance in gastric cancer cells. However, the role and molecular mechanism of ZJW in gastric cancer under hypoxia remain poorly understood. The aim of this study was to investigate the anti-cancer effects of ZJW on GC development and its underlying mechanisms.</p><p><strong>Materials and methods: </strong>Exosomes were isolated by differential centrifugation and characterized by transmission electron microscopy and Western blotting. Quantitative real-time PCR was used to measure miR-30a levels. CCK-8, colony formation assays, and flow cytometry (FCM) analysis were performed to investigate the effects of hypoxia-induced exosomes on cisplatin resistance. We used a specific exo-miR-30a inhibitor to explore the role of this miRNA in the transfer of chemoresistance from hypoxic to normoxic cells. Inhibition rates in tumor in vitro assays were measured, and xenograft models were established to investigate the effect of exosomes derived from ZJW treatment on GC chemotherapy sensitivity.</p><p><strong>Results: </strong>Exosomes derived from hypoxic, cisplatin-resistant gastric cancer cells promote cisplatin resistance in normoxic gastric cancer cells, which is inhibited by ZJW.</p><p><strong>Discussion: </strong>This study reveals a novel mechanism whereby inhibition of miR-30a in hypoxic exosomes reversed the chemoresistance effect by inhibiting the activation of Hedgehog-mediated PD-L1 signaling.</p><p><strong>Conclusion: </strong>These results indicate that hypoxia-induced exosomal miR-30a, derived from GCresistant drug cells, may promote chemoresistance in gastric cancer cells by activating Hedgehog- mediated PD-L1 signaling and can be attenuated by the involvement of ZJW.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198549","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":"YBX1 Enhances the Stability of TM4SF1 in an m5C-Dependent Manner to Promote Bladder Cancer Proliferation and Glycolysis.","authors":"Hong Li, Yu Liang, Jian Tang, Hongmei Luo, Yi Wang","doi":"10.2174/0113862073392269250825105059","DOIUrl":"https://doi.org/10.2174/0113862073392269250825105059","url":null,"abstract":"<p><strong>Introduction: </strong>Y-box binding protein 1 (YBX1), an RNA-binding protein capable of recognizing the 5-methylcytosine (m5C), plays a role in the development and progression of various cancers. In this study, we aim to investigate the functional mechanism of YBX1-mediated m5C modification in Bladder Cancer (BCa).</p><p><strong>Methods: </strong>The impact of YBX1 on glycolysis and biological functions in BCa cells was evaluated through a set of in vitro experiments. The underlying mechanisms involving YBX1, Transmembrane 4 L six family 1 (TM4SF1), and β-catenin/C-myc in BCa and their relationship were investigated using RNA immunoprecipitation (RIP), m5C-RIP, Actinomycin D, and luciferase reporter gene assays.</p><p><strong>Results: </strong>BCa cells exhibited elevated expression levels of YBX1 compared to human transitional bladder epithelial cells. YBX1 knockdown inhibited BCa cell proliferation, migration, and invasion while also attenuating glycolytic activity, as evidenced by reduced glucose uptake, lactic acid production, and ATP synthesis. Mechanically, we found that YBX1-dependent m5C modification promoted the stability of TM4SF1 mRNA, thereby upregulating TM4SF1 expression and subsequently activating the β-catenin/C-myc signaling. Furthermore, we discovered that overexpression of β-catenin could reverse the inhibitory effects of TM4SF1 silencing on proliferation and glycolysis in BCa cells.</p><p><strong>Discussion: </strong>This study has refined the mechanism of BCa progression, but the clinical significance and in vivo functions of the YBX1/TM4SF1 axis still require further verification.</p><p><strong>Conclusion: </strong>YBX1 stabilizes TM4SF1 mRNA via m5C modification in BCa, activating β- catenin/c-Myc signaling to drive tumor growth and glycolysis. This reveals a novel therapeutic target for BCa.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198539","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 the Therapeutic Mechanism of Chai-hu Long-gu Mu-li Decoction for Treating Insomnia and Anxiety Disorders based on Network Pharmacology and Experimental Validation.","authors":"Shaoyi Fan, Guodong Ruan, Chen Sun, Yuxuan Luo, Yiwei Chen, Xuejun Hu, Lei Cai, Fuping Xu","doi":"10.2174/0113862073388549250828182807","DOIUrl":"https://doi.org/10.2174/0113862073388549250828182807","url":null,"abstract":"<p><strong>Introduction: </strong>Chai-hu Longgu Muli decoction (CLMD) is a classic traditional Chinese herbal formula that has achieved good curative effects in treating insomnia and anxiety disorders clinically. However, the dual-targeting mechanism of CLMD on these two distinct diseases remains unclear. This study aims to explore the potential therapeutic effects and underlying mechanism of CLMD on insomnia and anxiety through the integration of network pharmacology, molecular docking, and zebrafish experiments.</p><p><strong>Methods: </strong>By combining network pharmacology and molecular docking, an integrative method was employed to analyze the potential molecular mechanism, and therapeutically effective components of CLMD on both insomnia and anxiety. In the verification experiment, the caffeineinduced insomnia and anxiety model of zebrafish was constructed to further verify the common mechanism underlying the dual-effects of CLMD.</p><p><strong>Results: </strong>A total of 97 dual-effects active compounds and 118 common targets of CLMD were identified. The targets with a higher degree were identified through the PPI network, including IL6, AKT1, TNF, ALB, and TP53. KEGG pathway analysis demonstrated that these targets were correlated to Neuroactive ligand-receptor interaction, TNF signaling pathway, Dopaminergic synapse, and PI3K-Akt signaling pathway. Results of molecular docking indicated good binding affinity of CLMD to IL6, AKT1, and TNF. Animal experiments showed that CLMD markedly altered sleep/wake behavior, decreased thigmotaxis (an indicator of anxiety levels), and also significantly reduced the expression of TNF-α after treatment.</p><p><strong>Discussion: </strong>The findings suggest that the dual therapeutic effects of CLMD on insomnia and anxiety were predominantly related to the regulation of neurotransmission and inflammatory response.</p><p><strong>Conclusion: </strong>This study provides new insight into the molecular mechanisms underlying the homotherapy- for-heteropathy efficacy of CLMD in treating both insomnia and anxiety.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112149","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":"Decoding Barberry Root's Therapeutic Network: A Synergistic Solution for IBS-D.","authors":"Qi Yan, Xufei Wang, Huijiao Jiang, Xuan Zhou, Xiangwei Wu, Xueling Chen","doi":"10.2174/0113862073421977250903053304","DOIUrl":"https://doi.org/10.2174/0113862073421977250903053304","url":null,"abstract":"<p><strong>Introduction: </strong>Barberry Root (Sankezhen, SKZ), a traditional Uyghur herb from Xinjiang, China, has been shown to alleviate diarrhea-predominant irritable bowel syndrome (IBSD); however, its molecular mechanisms remain unclear. This study aimed to systematically predict SKZ's therapeutic targets and pathways for IBS-D using computational and experimental integration.</p><p><strong>Methods: </strong>Active SKZ compounds and targets were sourced from TCM-Suite, BATMAN-TCM, and related databases. IBS-D targets were identified via DisGeNET and GeneCards, etc. Protein- Protein Interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Molecular docking and 100-ns Molecular Dynamics (MD) simulations validated compound-target stability. In vitro (LPS-induced RAW264.7 macrophages) and in vivo (IBS-D model rats, isolated intestinal segments) experiments verified SKZ's effects.</p><p><strong>Results: </strong>Fifteen bioactive compounds and 85 overlapping targets were identified, with four key compounds [(R)-Reticuline, Ferulic acid 4-O-glucoside, Magnoflorine, SW 7] and 15 hub targets (e.g., ESR1, EGF, ALB) prioritized. Enrichment analyses linked targets to inflammation and intestinal motility pathways. Docking showed strong binding affinities (<-8.0 kcal/mol), and MD simulations confirmed stability. SKZ suppressed inflammatory mediators, downregulated CHAT/C-FOS/5-HT3R/5-HT4R mRNA, and antagonized acetylcholine/barium chloride-induced intestinal contractions.</p><p><strong>Discussion: </strong>The findings highlight SKZ's synergistic role in ameliorating IBS-D via multipathway regulation, consistent with existing research on inflammation and neurotransmission, though limitations include the need for further validation of individual compounds.</p><p><strong>Conclusion: </strong>SKZ exerts synergistic therapeutic effects on IBS-D by ameliorating inflammation and regulating neurotransmission and intestinal motility, potentially via NF-κB/MAPK, COX- 2/PGE2, cholinergic/5-HT, and calcium/potassium channel pathways, forming a multidimensional network.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079882","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":"Isolation, Structural Elucidation of Small-molecule Sugars from the Seeds of Licorice.","authors":"Le Li, Jianping Yong, Yunsheng Fu, Canzhong Lu, Danian Tian","doi":"10.2174/0113862073401947250716152228","DOIUrl":"https://doi.org/10.2174/0113862073401947250716152228","url":null,"abstract":"<p><strong>Introduction: </strong>Much work on the chemical components and biological activities of licorice roots has been carried out, and many compounds have been isolated and confirmed from licorice roots already. However, little research on the isolation and confirmation of the chemical components from the seeds of licorice has been carried out till now. This work focuses on discovering new compounds from the seeds of licorice for the development of new drugs or drug candidates.</p><p><strong>Methods: </strong>The extract of the licorice seeds was isolated by column chromatography (CC) together with recrystallization to obtain the pure compounds. Their structures were elucidated by NMR and single crystal X-ray diffraction (SC-XRD).</p><p><strong>Results: </strong>Seven small-molecule sugars (1-7) [Methyl α-D-Galactopyranoside (1), Sucrose (2), α- L-Rhamnose (3), D-Xylose (4), α-D-Glucose (5), D-Galactose (6), D-Lyxose (7)] were isolated from the seeds of licorice for the first time. Their structures were confirmed by NMR and SCXRD.</p><p><strong>Discussion: </strong>In this work, we isolated small-molecule sugars (1-7) from the seeds of licorice for the first time, and methyl α-D-Galactopyranoside (1) is a very scarce compound from the natural plant medicines, which was isolated from the seeds of licorice.</p><p><strong>Conclusion: </strong>The roots of licorice have been used in clinics as a Chinese traditional plant medicine for a long time, and much work on the chemical components and biological activities have been conducted. However, little research on the isolation and confirmation of the chemical components from the seeds of licorice has been carried out. This work provides the scientific basis for in-depth research on licorice seeds.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063395","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":"Scutellaria barbata Flavonoids Promote Nerve Regeneration and Ameliorate the Rats' Impaired Spatial Memory via the Ras-ERK-CREB Signaling Pathway.","authors":"Liu Xinyang, Ma Shuai, Liu Yuling, Huo Jing, Gao Yang, Cheng Jianjun, Shang Yazhen","doi":"10.2174/0113862073381254250806100557","DOIUrl":"https://doi.org/10.2174/0113862073381254250806100557","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to investigate whether Scutellaria barbata flavonoids (SBFs) enhance nerve regeneration and ameliorate spatial memory impairment in an Alzheimer's disease (AD) rat model, as well as the effective mechanism mediated by Ras-ERK-CREB signaling pathway.</p><p><strong>Methods: </strong>An AD model of rats was established by intracerebroventricular injection of Aβ25-35 combined with AlCl3 and RHTGF-β1 (composited Aβ). The successful model rats were screened with the Morris water maze and randomly divided into the model group, 140 mg/kg SBFs group, and 0.5 mg/kg Rolipram group. The spatial memory ability of the rats was tested with the Barnes maze. Nissl bodies in the nerve cells were observed with crystal violet staining. The expression of NeuroD1 was detected by immunohistochemistry. The mRNA and proteins of molecules in Ras-ERK-CREB signaling pathway were measured using real-time quantitative PCR and western blotting methods, respectively. CREB activator Rolipram was used as a positive control.</p><p><strong>Results: </strong>Intracerebroventricular injection of composited Aβ resulted in the rats' spatial memory impairment, both the density of intracellular Nissl bodies and the protein expression of NeuroD1 decreased, as well as the mRNA and protein expression of molecules disorder in Ras-ERKCREB signaling pathway in the brain. However, SBFs can enhance the spatial memory, increase Nissl body density, and NeuroD1 protein expression, and regulate the abnormal mRNA and protein expression levels of molecules in Ras-ERK-CREB signaling pathway induced by composited Aβ. Rolipram showed similar effects to SBFs.</p><p><strong>Conclusion: </strong>SBFs promote nerve regeneration and enhance spatial memory by regulating the Ras-ERK-CREB signaling pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063505","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":"Effects of Limb Remote Ischemic Conditioning and Asafoetida on Biochemical, Histological, and Neurological Parameters and Metabolic Gene Expression in Diabetic Rats.","authors":"Seyyed Majid Bagheri, Elham Hakimizadeh, Mohammad Allahtavakoli","doi":"10.2174/0113862073379526250813000428","DOIUrl":"https://doi.org/10.2174/0113862073379526250813000428","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is a global metabolic disease caused by several factors including an incorrect lifestyle. The presence of antioxidant and anti-inflammatory compounds has made asafoetida a suitable candidate for anti-diabetes studies. On the other hand, Limb Remote Ischemic Conditioning (LRIC) is a new method that has been taken into consideration in recent years due to the activation of anti-apoptotic, anti-inflammatory, and antioxidant pathways.</p><p><strong>Objective: </strong>According to this evidence, we aim to investigate the antidiabetic effects of asafoetida and LRIC on type 2 diabetic rats.</p><p><strong>Materials and methods: </strong>Diabetes was induced using a high-fat diet (60%) and streptozotocin injection (35mg/kg), and the animals were divided into five groups. The treatment groups included asafoetida 50mg/kg, LRIC group and asafoetida 50 mg/kg + LRIC group. Two groups were considered normal and diabetic control groups. At the end of the experiment, glucose, lipid profile and liver enzymes, as well as tissue changes in the liver and pancreas were examined. The expression levels of adiponectin, GLUT4, insulin receptor and AMPK in skeletal muscle as well as damage to peripheral and central nerves were investigated.</p><p><strong>Results: </strong>The results showed that in the asafoetida and asafoetida + LRIC groups, a significant improvement was observed in the measured parameters, and no significant effect was observed in the LRIC group.</p><p><strong>Conclusion: </strong>These results indicate that, contrary to some notions about the effect of LRIC on the improvement of diabetes, this method cannot reduce blood sugar, fat, and other complications caused by diabetes.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063349","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}