AQUACULTURE
·
2025
·
IF 3.9
Shenye Qu,Yihang Liu,Kaiyuan Lu,Yunlong Qin,Jiacheng Qin,Jietao Liu,Xiaohu Wu,Gaoxue Wang,Fei Ling
Ichthyophthirius multifiliis infections constitute a critical challenge demanding urgent resolution in global aquaculture systems. Although over 20 chemicals and natural products have demonstrated efficacy against I. multifiliis in the past two decades, the translation of these findings into clinically viable antiparasitic agents has progressed slowly, with the development of novel potent therapeutics remaining a major challenge. In this study, six novel magnolol-derived compounds were rationally designed through structural optimization of the magnolol scaffold. All synthesized compounds exhibited potent antiparasitic activity against both theront and tomont stages of I. multifiliis . Compound C1 showed superior efficacy to magnolol, with 18-fold and 26-fold lower EC 50 values against theronts (0.035 mg/L) and tomonts (0.024 mg/L) in vitro, respectively. Notably, these activity surpassed the potency of malachite green. Moreover, compound C1 showed lower toxicity than malachite green. ADMET and Density functional theory (DFT) calculations revealed that compound C1 had a favorable electrostatic potential (ESP) distribution and a lower energy gap between Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), indicating good druggability. Integrated in silico strategy identified Mapk3 (mitogen-activated protein kinase 3) as the primary therapeutic target mediating C1's antiparasitic effects. Protein-Protein Interaction (PPI) network analysis, along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, suggested that compound C1 might disrupt lipid metabolism and lipoxygenases pathways by modulating Mapk3 expression, thereby exerting potent antiparasitic effects. These findings establish compound C1 as the most potent anti- I. multifiliis agent reported to date. Its potential application in aquaculture may provide valuable insights for addressing this critical bottleneck issue.
研究领域:
药理学
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水产养殖学
·
计算化学
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DOI
高影响因子
Biomed Research International
·
2022
·
IF 3.246
Shisheng Jiang,Chaoming Huang,Shulin Wang,Biyun Huang,Dan Wu,Guodong Zheng,Yi Cai
Objective. Through a network pharmacology method, we screened the main active compounds of Citri Reticulatae Pericarpium (CRP), constructed a drug-ingredient-disease-target network, explored the molecular mechanism of its treatment of myocardial hypertrophy, and validated it by using molecular biology approach. Methods. Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards were utilised to collect the effective component in CRP and the targets of CRP and myocardial hypertrophy. The STRING database constructed the protein interaction network. The drug-ingredient-disease-target network was outlined by the Cytoscape 3.9.0 software. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Real-time PCR (RT-PCR) and Western blotting were utilised to determine the mRNA and protein level of the critical targets of CRP therapy for myocardial hypertrophy. Results. We found that five practical components of CRP exerted therapeutic effects on myocardial hypertrophy by modulating 41 targets. Further analysis revealed that naringenin was the essential active compound in CRP that regulated myocardial hypertrophy. In addition, we showed that the active compounds of CRP might exert antihypertrophy effects via regulating essential target proteins such as AKT1-, MAPK3-, PPARA-, PPARG-, and ESR1-mediated signaling pathways such as cell proliferation, nuclear receptor activation, and oxidative stress. The molecular biology experiments demonstrated that naringenin inhibited the mRNA level of NPPA and NPPB induced by Ang II and regulated related targets such as AKT1, MAPK3, PPARA, PPARG, and ESR1. Conclusion. CRP could inhibit myocardial hypertrophy through multitarget and multiapproach.
研究领域:
药理学
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分子生物学
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中医药学
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心脏病学
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产品关联
DOI
PubMed
高影响因子
Computational and Mathematical Methods in Medicine
·
2022
·
IF 2.809
Zhulin Wu,Jianyuan Kang,Wanjun Tan,Chunshan Wei,Li He,Xiaoyan Jiang,Lisheng Peng
Objective. Traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese materia medica formulas with the effect of “Yiqi Jianpi” (replenishing qi and strengthening spleen) or “Jiedu” (removing toxicity) have been proved to be effective in treating HCC. However, mechanisms of these formulas in treating HCC remain unclear. In this paper, our goal is to explore the antitumor activity and its molecular mechanisms of Yiqi Jianpi Jiedu (YQJPJD) formula against HCC. Methods. The bioactive ingredients and targets of YQJPJD formula and HCC targets were screened by five Chinese materia medicas and two disease databases, respectively. The network pharmacology was utilized to construct the relationship network between YQJPJD formula and HCC, and the mechanisms were predicted by the protein-protein interaction (PPI) network, pathway enrichment analysis, bioinformatics, and molecular docking. Numerous in vitro assays were performed to verify the effect of YQJPJD formula on HCC cells, cancer-associated targets, and PI3K/Akt pathway. Results. The network relationship between YQJPJD formula and HCC suggested that YQJPJD formula mainly regulated the potential therapeutic targets of HCC by several key bioactive ingredients (e.g., quercetin, luteolin, baicalein, and wogonin). PPI network, bioinformatics, and molecular docking analyses displayed that YQJPJD formula may play an anti-HCC effect through key targets such as MAPK3, RAC1, and RHOA. Additionally, pathway analysis demonstrated that YQJPJD formula could play an anti-HCC effect via multiple pathways (e.g., PI3K-Akt and hepatitis B). Experimental results showed that YQJPJD formula could effectively inhibit the proliferation, migration, and invasion of HCC cells and promote HCC cell apoptosis in a concentration-dependent manner. Moreover, YQJPJD formula could decrease the mRNA expression of β-catenin, MAPK3, and RHOA and the protein expression of phosphorylated PI3K and Akt. Conclusion. YQJPJD formula mainly exerts its anti-HCC effect through multiple bioactive ingredients represented by quercetin, as well as multiple pathways and targets represented by PI3K/Akt pathway, β-catenin, MAPK3, and RHOA.
研究领域:
药理学
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肿瘤学
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中医药
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Metabolites
·
2024
·Vol. 14
·期 4
·224
·
IF 3.4
Jianing Ren,Jing Dai,Yue Chen,Zhenzhen Wang,Ruyi Sha,Jianwei Mao,Yangchen Mao
Rice (Oryza sativaL.) is one of the primary sources of energy and nutrients needed by the body, and rice resistant starch (RRS) has been found to have hypoglycemic effects. However, its biological activity and specific mechanisms still need to be further elucidated. In the present study, 52 RRS differential metabolites were obtained from mouse liver, rat serum, canine feces, and human urine, and 246 potential targets were identified through a literature review and database analysis. A total of 151 common targets were identified by intersecting them with the targets of type 2 diabetes mellitus (T2DM). After network pharmacology analysis, 11 core metabolites were identified, including linolenic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, lithocholic acid, lithocholylglycine, glycoursodeoxycholic acid, phenylalanine, norepinephrine, cholic acid, and L-glutamic acid, and 16 core targets were identified, including MAPK3, MAPK1, EGFR, ESR1, PRKCA, FYN, LCK, DLG4, ITGB1, IL6, PTPN11, RARA, NR3C1, PTPN6, PPARA, and ITGAV. The core pathways included the neuroactive ligand–receptor interaction, cancer, and arachidonic acid metabolism pathways. The molecular docking results showed that bile acids such as glycoursodeoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, lithocholic acid, deoxycholic acid, and cholic acid exhibited strong docking effects with EGFR, ITGAV, ITGB1, MAPK3, NR3C1, α-glucosidase, and α-amylase. In vitro hypoglycemic experiments further suggested that bile acids showed significant inhibitory effects on α-glucosidase and α-amylase, with CDCA and UDCA having the most prominent inhibitory effect. In summary, this study reveals a possible hypoglycemic pathway of RRS metabolites and provides new research perspectives to further explore the therapeutic mechanism of bile acids in T2DM.
研究领域:
药理学
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生物化学
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分子生物学
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糖尿病研究
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营养学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Ting-Ting He,Xin Li,Jie-Zhi Ma,Yuan Yang,Shiye Zhu,Jianhua Zeng,Lin Luo,Yu-Long Yin,Lin-Ying Cao
Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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