COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
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2024
·Vol. 27
·期 13
·1919-1929
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IF 1.6
Zhang Fei,Chu Mingliang,Liu Jiemin,Zhao Qi,Zhu Yanqiu,Wu Xuefang
Aim: The study aimed to study the potential roles and mechanisms of shikonin in gastric cancer by network pharmacology and biological experiments. Methods: The key genes and targets of shikonin in gastric cancer were predicted by network pharmacology and molecular docking study.
The effect of shikonin on the proliferation, migration, and invasion of gastric cancer cells was detected by the CCK8 method, and wound healing and transwell assays. The expression levels of c-Myc and Yap-1 were detected via western blotting in gastric cancer cells after shikonin intervention.
Results: The results of network pharmacology revealed the key target genes of shikonin on gastric cancer cells to be c-Myc, Yap-1, AKT1, etc. GO and KEGG analysis showed regulation of cell migration, proliferation, adhesion, and other biological processes, including the PI3K-Akt signaling
pathway, HIF-1 signaling pathway, necroptosis, and other cancer pathways. Molecular docking showed shikonin to be most closely combined with protooncogenes c-Myc and Yap-1. In vitro experiments showed that the proliferation rate, migration, and invasion ability of the gastric cancer cell group
decreased significantly after shikonin intervention for 24h. The expression levels of c-Myc and Yap-1 in gastric cancer cells were found to be significantly decreased after shikonin intervention. Conclusion: This study showed protooncogenes c-Myc and Yap-1 to be the core target genes
of shikonin on gastric cancer cells. Shikonin may suppress gastric cancer cells by inhibiting the protooncogenes c-Myc and Yap-1. This suggests that shikonin may be a good candidate for the treatment of gastric cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
RESEARCH IN VETERINARY SCIENCE
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2025
·
IF 1.8
Zhiqin Liu,Yufeng Xu,Wei Liu,Lin Wang,Zhen Dong,Jianguo Zeng
Diarrhoea remains a major public health concern, particularly affecting young children and livestock. Macleaya cordata protopine total alkaloids (MPTA), a standardized extract approved in China for poultry diarrhoea, has demonstrated anti-inflammatory properties in intestinal disorders. The study aims to investigate the antidiarrheal mechanism of MPTA using castor oil- and E. coli -induced diarrhoea models in mice. We first tested MPTA for acute oral toxicity. Subsequently, the effect of MPTA on castor oil- and E. coli -induced diarrhoea in mice based on LD 50 results. Network pharmacology analysis and target competition assays (inhibitors and antagonists) were integrated to identify targets for MPTA's antidiarrheal effects. Molecular docking was used to verify the binding ability of MPTA components to these receptors. The LD 50 of MPTA was determined to be 426.1 mg/kg. The optimal MPTA activity was found at 8 mg/kg in both castor oil and in infectious models. Network pharmacology analysis revealed potential targets and pathways of MPTA against intestinal motility. The impact of MPTA on cholinergic, serotonin, dopaminergic, and adrenergic receptors was assessed using standard inhibitors and agonists to induce intestinal smooth muscle contractions or relaxations. Molecular docking confirmed the binding ability of MPTA components to these receptors. In conclusion, MPTA exhibits significant antidiarrheal effects in both castor oil and E. coli -induced diarrhoea models. Its mechanism may involve modulation of cholinergic, serotonin, dopaminergic, and adrenergic receptors, as well as inhibition of ion channels and anti-inflammatory actions. These findings highlight the potential of MPTA as a novel therapeutic agent for diarrhoea.
研究领域:
药理学
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生物医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
·
IF 6.1
Zhiqi Zhang,Hanchuan Wang,Zhulingzhi Kuang,Hui Liang,Yan Ju,Dali Meng
Abrus mollis Hance is a characteristic medicinal herb which is used in Guangdong and Guangxi provinces of China for making soup, medicinal meals, and herbal tea to treat dampheat jaundice and rib discomfort. Current phytochemical study on A. mollis led to the isolation of four new flavones, mollisone A-D (1–4), and thirty two known compounds (5–36). Their structures were characterized by an extensive analysis of spectroscopic data including IR, UV, HR-ESI-MS, and 1D and 2D NMR, as well as electronic circular dichroism calculation. In addition, in order to initially understand their biological activities for traditional applications, in vitro antioxidant and hepatoprotective tests were carried out, whose results illustrated that 25 compounds had significant free radical scavenging ability, and compounds 13 and 16 exhibited protective activities on D-GalN-induced LO2 cell damage than the positive control. Moreover, network pharmacological analysis revealed that the hepatoprotective activity of A. mollis involved multitargets and multipathways such as PI3K/Akt, MAPK, and JAK-STAT pathways and various biological processes such as positive regulation of phosphorylation and regulation of kinase activity. These results suggested that this species could serve as a potential hepatoprotective agent for functional food or medicinal use.
研究领域:
中药学
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药理学
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植物化学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-11
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IF 3.9
Hu Lili,Wu Na,Wang Jue,Cai Donghui
The anti-inflammatory effect of phellodendrine (PHE), derived from Phellodendri Chinensis Cortex, has been verified in previous studies. Major depressive disorder (MDD) is associated with immune dysregulation and inflammatory processes. This study aimed to explore the therapeutic effects of PHE on MDD through network pharmacology and experimental validation. Multiple databases were used to predict the targets of PHE and MDD. The intersection targets between PHE and MDD were obtained to identify as targets for PHE against MDD, followed by protein–protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Molecular docking was applied to further confirm the anti-MDD effects of PHE. The mitochondrial DNA (mtDNA) copy number, inflammatory cytokines and pathway-related mRNA expressions in PC12 cell were determined via quantitative PCR (qPCR) and enzyme-linked immunosorbent assay to verify our finding. Thirty-eight intersection targets were obtained between PHE and MDD. PHE exerted an anti-MDD effect by regulating SLC6A4, SLC6A3, SLC6A2, MAOA and other targets through serotonergic synapse, salivary secretion, dopaminergic synapse, and cAMP signalling pathway. In vitro, PHE induced an increment in mtDNA copy number compared with the CORT group. PHE affected the levels of IL6 and IL1β with different concentrations. The mRNA levels of CHRM1, HTR1A and key targets of the PI3K/Akt signalling pathway were also influenced. Our research reveals novel mechanisms underlying the anti-MDD effects of PHE through network pharmacology and experiments, which provides a new direction for the development of antidepressants.
研究领域:
药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Biology-Basel
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2025
·Vol. 14
·期 1
·51
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IF 3.5
Ferry Saputra,Tzu-Ming Tseng,Franelyne P. Casuga,Yu-Heng Lai,Chih-Hsin Hung,Chung-Der Hsiao
Simple SummaryMany studies have been developed to calculate the blood flow velocity in adult zebrafish. However, the current method requires high-cost equipment a lot of training before it can be replicated. In this study, we provide a simple, cheap, and non-invasive method to enable the measurement of zebrafish blood flow velocity. By applying the same method as the one previously developed for larvae zebrafish, blood flow velocity can be measured and its sensitivity validated by performing an experiment under several ambient temperature conditions, as well as the presence of a toxicant. The applicability of this method was also checked by applying the same method to other fish. Overall, this method provides an easy, cheap, and robust method that can be used by low- to medium-scale laboratories to contribute to knowledge in the relevant fields.Blood flow is an important physiological endpoint to measure cardiovascular performance in animals. Because of their innate transparent bodies, zebrafish is an excellent animal model for assessing in vivo cardiovascular performance. Previously, various helpful methods for measuring blood flow in zebrafish larvae were discovered and developed. However, an optimized method to measure blood flow in adult zebrafish has not been reported. In this paper, the tail fin region was selected as target for blood flow measurements using the Trackmate method, provided by ImageJ platform. Based on power statistic calculations, the aortic vessel at the tail base was selected, and other parameters, such as ambient temperature, were investigated for method standardization, in order to minimize experimental variation. The method was also validated using fenpropathrin and ponatinib, which showed some cardiac alterations in a previous zebrafish study. We also checked the versatility of this method by following the same setup in black tetra and medaka and found that this method performed well. However, our results show that heavy pigmentation, like that found in tiger barb, and overlapping vessels, like those in parrot fish, make it hard for this method to perform well. Overall, an optimized protocol was used for the first time to measure blood flow velocity in adult wild-type zebrafish without the aid of transgenic lines or fluorescent dye.
研究领域:
生物学
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医学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
Foods
·
2023
·Vol. 12
·期 16
·3000
·
IF 5.2
Jialiang Chen,Zheng Zhou,Ping Li,Shuhong Ye,Wei Li,Ming Li,Lin Zhu,Yan Ding
Type 2 diabetes mellitus (T2DM) has developed into an important health concern worldwide. The discovery of phlorotannins and their efficacy in the treatment of T2DM has become a hotspot for research in various fields. In this study, the potential phlorotannins and mechanism of six brown algae against T2DM were in-depth investigated using biological activity assays, LC-MS, and network pharmacology. First, the ethyl acetate fraction (EA frac.) showed high polyphenolic content and possessed significantly antioxidant and enzyme inhibitory abilities. Further, a total of fifty-nine peaks were obtained from six EA fracs. via UPLC-QE-MS/MS analysis, and fifteen of them were identified as phlorotannins and their isomers or derivatives. In detail, the chemical structures of six phlorotannins were inferred as dibenzodioxine-1,3,6,8-tetraol, bifuhalol, dioxinodehydroeckol, eckol, fucofurodiphlorethol, and fucotriphlorethol; three phlorotannin isomers were deduced to be fucophlorethol, trifucol, triphlorethol A, or triphlorethol B; and the phlorotannin derivative ofm/z263 was determined to be dibenzodioxine-1,2,3,6,8-pentanol or dibenzodioxine-1,2,4,5,7-pentanol. Moreover, 43 T2DM-related targets acted on by these chemicals were identified, and the function of phlorotannin to prevent and treat T2DM was elucidated in a holistic way based on the established compound-target-disease network, and GO function and KEGG pathway enrichment analysis.Keywords:phlorotannins;T2DM;UPLC-QE-MS/MS;network pharmacology
研究领域:
药理学
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生物化学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
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2024
·Vol. 17
·期 12
·1675
·
IF 4.3
Yaping Chen,Qiuqi Wen,Meng Lin,Bing Yang,Liang Feng,Xiaobin Jia
Objectives:Traditional Chinese Medicine (TCM) is recognized for its complex composition and multiple therapeutic targets. However, current pharmacological research often concentrates on extracts or individual components. The former approach faces numerous challenges, whereas the latter oversimplifies and disregards the synergistic effects among TCM components. This study aims to investigate the scientific validity of focusing on the active constituent in TCM efficacy research, usingPueraria lobata(P. lobata) as a case study.Methods:Through spectrum-effect correlation analysis, network pharmacology, and molecular docking, five active ingredients ofP. lobatawere identified: puerarin, formononetin, tuberosin, 4′,7-dihdroxy-3′-methoxyisoflavone, and Daidzein-4,7-diglucoside. These ingredients were combined to form an active constituent, which was subsequently tested in vitro and in vivo.Results:In in vitro, the active constituent exhibited superior effects in enhancing glucose consumption and glycogen synthesis compared to both theP. lobataextract and individual components. In vivo experiments demonstrated that medium and high doses of the active constituent were significantly more effective thanP. lobataextract, with effects comparable to those of metformin in reducing blood sugar levels.Conclusions:The active constituent effectively improves T2DM by lowering blood glucose levels, promoting glycogen synthesis, and modulating glycolipid metabolism. Both in vitro and in vivo studies indicate that it outperformed theP. lobataextract and individual components. This study establishes the scientific validity and feasibility of utilizing the active constituent as the focus for investigating the efficacy of TCM, thereby offering novel insights and a new research paradigm for future TCM investigations.
研究领域:
药理学
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中医药研究
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糖尿病
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植物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Acupuncture and Herbal Medicine
·
2024
·Vol. 4
·期 2
·243
·
IF 0
Wu Jianzhi,Ma Zhi,Zhang Yinhao,Duan Shuni,Sun Rong,Liu Runping,Li Yijie,Li Xiaojiaoyang
Objective: Drug-induced liver injury (DILI) is the leading cause of acute liver failure and poses a significant challenge to human health. Rhubarb ( Rheum officinale Baill . DaHuang) has been clinically used for its heat-clearing and diuresis-promoting effects. However, its toxic effects on different organelles in the liver require further validation. Methods: We analyzed the potential targets affecting hepatotoxicity in rhubarb and the potential damage relationship with five major organelles, including microsomes, mitochondria, endoplasmic reticulum (ER), Golgi apparatus (GA), and lysosomes through Integrated Traditional Chinese Medicine (ITCM)/HERB databases and network pharmacology. We isolated and purified different organelles, incubated them with different fractions and monomers of rhubarb in an adenosine triphosphate (ATP) culture system and examined the structural and functional changes in the organelles using particle size analysis and molecular biological experiments to investigate whether rhubarb affects the damage and rupture of major organelles in the liver. Results: By combining virtual predictions and experimental verification, our research confirmed that emodin isolated from the anthraquinone of rhubarb, catechin in the tannins of rhubarb, and palmitic acid in the organic acids of rhubarb caused the most significant functional and structural damage to the representative organelles. Among all the monomeric compounds, emodin caused the most damage to the microsome, mitochondria, ER, and lysosome; catechin induced microsome and GA damage; and palmitic acid caused the most damage to microsomes and GA in the liver, suggesting that rhubarb components may exert hepatotoxicity through multi-organelle injury. Conclusions: Our findings revealed that rhubarb has varying degrees of damaging effects on different organelles, which in turn affects cellular life activities by impairing organelle morphology and function. This study provides a theoretical basis and technical support for a refined analysis of the toxic components and targets of rhubarb. Export
研究领域:
中药学
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药理学
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细胞生物学
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生物化学
✓ 已验证
DOI
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2021
·Vol. 35
·期 18
·e9157
·
IF 2.419
Feng-Xiang Zhang,Yu-Lin-Lan Yuan,Shuang-Shuang Cui,Min Li,Rui-Man Li
Rationale Characterizing the functional mechanism of quality control marker (Q-marker) was of great importance in revealing the primary pharmacological mechanism of herbs or the other complex system, and drug-related metabolites always contribute to the pharmacological functions. Cortex Phellodendri was used as a core herb in the treatment of diabetes mellitus (DM). As a Q-marker of Cortex Phellodendri, the role of phellodendrine in DM was still unclear. Thus, the characterization of phellodendrine-related metabolites in vivo and the subsequent induced functional mechanism exerted great importance in elucidating the anti-DM mechanism of Cortex Phellodendri. Methods An ultra-high-performance liquid chromatography-coupled time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method was developed to profile metabolites of phellodendrine in rats. The potential pharmacological mechanism against DM was predicted by network pharmacology. Results A total of 19 phellodendrine-related metabolites were screened out in rats for the first time. Among them, M4 , M5 , M9 , and M12 were regarded as the primary metabolites. Meanwhile, phase I metabolic reactions of hydroxylation, demethylation, and isomerization and phase II reactions of glucuronidation and sulfation occurred to phellodendrine; glucuronidation and hydroxylation were the two main metabolic reactions. Moreover, the potential targets of phellodendrine and three main metabolites ( M4 , M5 , and M12 ) were predicted by a network pharmacological method, and they mainly shared 52 targets, including PDE5A, CHRNA3, SIGMAR1, F3, ESR1, DRD1, DRD2, DRD3, and DRD4. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, and cAMP signaling pathway were regarded as the core mechanism of phellodendrine to treat DM. Conclusion The metabolic feature of phellodendrine in vivo was revealed for the first time, and its anti-DM mechanism information for further pharmacological validations was also supplied. It also gave a direction to further elucidation of pharmacological mechanism of Cortex Phellodendri in treating DM.
研究领域:
药理学
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代谢组学
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Aining Yin,Yu Fu,Tingxin Wang,Honglin Li,Xiufang Wang,Xueke Ye,Peipei Dong,Wei Yao
Ethnopharmacological relevance FZLFR was derived from a classic traditional Chinese medicine recipe, the Shiquan-Dabu decoction. FZLFR is commonly used in clinical practice to address muscle loss and associated cancer cachexia. However, the mechanism of by which FZLFR acts in cancer cachexia remains unclear. Aim This study aimed to assess the effects and explore the potential mechanism of action of FZLFR in treating cancer cachexia. Methods Cancer cachexia was induced by inoculating Lewis lung carcinoma cells into the right flank of male C57BL/6 mice. The efficacy of FZLFR was evaluated by comparing changes in body weight, tumor mass, food intake, survival time, weight, and cross-sectional area of the gastrocnemius and anterior tibial muscles. Moreover, inflammatory cytokines, such as TNF-α and IL-6, were detected by ELISA. The chemical components of FZLFR were analyzed using ultra-performance liquid chromatography-coupled with time-of-flight mass spectrometry. Network pharmacology analysis was performed to screen the core targets and potential pathways involved in FZLFR treatment of cancer cachexia. Molecular docking was used to analyze the binding ability of the core targets and key compounds. The expression levels of core targets and targets correlated with skeletal muscle atrophy were also assessed using western blotting. Results FZLFR enhanced the food intake and survival rate of mice with cancer cachexia. It also alleviated tumor-induced body weight loss, tumor growth, and muscle fiber atrophy in these mice. Additionally, it improved the weight and cross-sectional area of the gastrocnemius and anterior tibial muscles. FZLFR down-regulated the serum levels of TNF-α and IL-6. UPLC-ESI-Q-TOF-MS analysis identified 184 compounds in FZLFR. Network pharmacology analysis predicted that TNF signaling pathway, ErbB signaling pathway and VEGF signaling pathway might be essential in FZLFR action. Molecular docking showed that kaempferol, upafolin, apigenin, and luteolin might play key roles in FZLFR treatment. Moreover, FZLFR decreased MAFBx1, MURF1, NF-κB, TWEAK, MAPK8, and EGFR expression levels. FZLFR enhanced the expression of VEGFA and ESR1, as demonstrated by western blotting. Conclusions FZLFR increased food intake and alleviated muscle atrophy in mice with cancer cachexia. The potential pharmacological mechanisms underlying its anticachexia effects include reducing inflammation, enhancing muscle vascular growth, inhibiting tumor angiogenesis, and modulating estrogen receptors.
研究领域:
民族药理学
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肿瘤学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Xiaodan Zhang,Lihong Zhou,Yulong Peng,Shiyu He,Zhen Mao,Jin Cai,Aobo Geng,Hong Yang,Peili Huang
Copper serves as an indispensable cofactor for all living organisms, and its excessive accumulation has been associated with a variety of diseases. Wilson’s disease (WD) serves as an illustrative example of copper toxicity in humans, frequently presenting with liver and/or neuropsychiatric symptoms. The current therapeutic drugs, penicillamine (PA) and zinc gluconate (ZnG), have constraints, and research on their combination efficacy remains insufficient. It has been reported that melatonin (MLT) plays a vital role in binding to transition metals and exhibits strong antioxidant capacity. To investigate the therapeutic efficacy of MLT and combined treatment, rats were randomly divided into the following seven groups: the control (Con) group, copper-laden model rat (Mod) group, PA-treated group, ZnG-treated group, MLT- treated group, PA-ZnG-treated group, and PA-MLT-treated group. Then potential mechanisms and targets were investigated using a combination of metabolomics and network pharmacology and verified by molecular docking and qPCR. The findings revealed that MLT and the combination significantly improved behavior, pathology and copper levels in copper-laden rats. The results of the metabolomics study showed that profoundly altered metabolites were identified, and alanine, aspartate and glutamate metabolism, pyruvate metabolism, citrate cycle (TCA cycle), and glycolysis/gluconeogenesis were explored. In addition, molecular docking showed that MLT had high binding affinity with key targets, and qPCR results revealed that MLT could reverse the mRNA expression of targets GOT2 and PKM2. It was concluded that MLT effectively improves brain injury in copper-laden rats, and this effect was linked with the altered features of the metabolite profiles.
研究领域:
神经科学
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药理学
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代谢组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2025
·
IF 2.8
Aiping Li,Xiaoyu Zhang,Zheng Ju,Tingting Luo,Ting Cui,Xuemei Qin,Guangzhen Liu
To elucidate the molecular mechanisms of the MIX (combined in proportion to the content in Astragali Radix (AR), named the MIX) repairing podocyte damage to ameliorate nephropathy. MTT assay and western blot analysis were used to evaluate the protective effects of MIX on MPC5 cells induced by Adriamycin (ADR). Screening of potential pharmacodynamic markers, relevant drugs and disease targets were conducted by using metabolomics combined with bioinformatics, and the most relevant metabolic pathways were identified by analyzing shared target and KEGG pathways. The key mechanism was subsequently validated by cell adhesion assays, western blot assays, and immunofluorescence staining. The results showed that the MIX has the capacity to repair adriamycin-induced damage in MPC5 cells, as evidenced by enhanced cell viability and synaptopodin expression. Additionally, the MIX shows promise in potentially reinstating the podocyte adhesion through the modulation of the expression of podocyte adhesion-related proteins linked to nucleotide metabolites. The MIX has the potential to beneficially affect podocyte injury by modulating the cell adhesion pathway, contributing to one of the pharmacodynamic mechanisms of AR treatment of nephrotic syndrome. This has implications for the development and utilization of AR resources and achievement the social benefit of empowering rural revitalization.
研究领域:
药理学
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代谢组学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）