scholarly journals Andrographolide Against Lung Cancer-New Pharmacological Insights Based on High-Throughput Metabolomics Analysis Combined with Network Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Luo ◽  
Li Jia ◽  
Jia-Wen Zhang ◽  
Dong-Jie Wang ◽  
Qiu Ren ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Throughput ◽  
Acid Metabolism ◽  
Pharmacological Action ◽  
Arachidonic Acid Metabolism ◽  
Metabolic Effects ◽  
Network Pharmacology ◽  
Control Group ◽  
Protective Effects ◽  
Metabolomics Analysis

Andrographolide (Andro) has known to treat various illnesses such as colds, diarrhea, fever and infectious diseases. However, the effect mechanism of Andro is still unclear. Therefore, we used high-throughput metabolomics analysis to discover biomarkers, metabolic profiles and pathways to reveal the pharmacological action and effective mechanism of Andro against lung cancer. The metabolic effects of Andro on lung cancer animal was explored by ultra-performance liquid chromatography-triple-time of flight/mass spectrometry (UPLC-TOF/MS) analysis. Our results showed that Andro exhibited significant protective effects against lung cancer. Compared with control group, a total of 25 metabolites biomarkers was identified in urine of model animals, which 18 of them were regulated toward the normal direction after Andro treatment, and network pharmacology analysis showed that they were related with 570 proteins. Biological pathways analysis showed that the 11 metabolism pathways were regulated by Andro treatment in lung cancer mouse, and amino acid metabolism and arachidonic acid metabolism have great potential as target pathways for Andro against lung cancer. It revealed that high-throughput metabolomics combined with network pharmacology analysis provides deeply insight into the therapeutic mechanisms of natural product for promoting medicine development and disease treatment.

scholarly journals Study on the Mechanism of Reducing Hepatotoxicity of Water-Grinding Realgar by Metabolomics, Morphology, and Chemical Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ting Han ◽  
Hui Zhang ◽  
Wenjuan Xu ◽  
Chunshuai Li ◽  
Min Wang ◽  
...  
Keyword(s):  
Acid Metabolism ◽  
Histopathological Examination ◽  
Liver Weight ◽  
Arachidonic Acid Metabolism ◽  
Control Group ◽  
High Dose ◽  
Grinding Method ◽  
Significant Toxicity ◽  
Male Wistar Rats ◽  
Metabolomics Analysis

Background. Realgar was usually selected as a substitute for arsenic trioxide to treat acute promyelocytic leukemia due to its higher effect without high cardiotoxicity. In traditional Chinese medicine (TCM), realgar is usually processed by the water-grinding method clinically, but the mechanism of realgar processing detoxification is still unclear. However, it is necessary to take safety and efficacy into account while evaluating a drug. Methods. Sixty male Wistar rats were divided into control group, realgar products-treated groups, and corresponding subgroups. Biochemistry analysis and histopathological examination were performed in the study, and plasma samples were collected from all the rats for metabolomics analysis. Results. No significant toxicity was observed in rats treated with 0.64 g/kg/day grinding realgar (G-r) and water-grinding realgar (WG-r). When the dose increased to 1.92 g/kg/day, the liver weight coefficients of the rats treated with G-r (HG-r: 3.65 ± 0.26%) and WG-r (HWG-r: 3.67 ± 0.14%) increased significantly and severe hepatic injury occurred in comparison to the control group (Group C: 3.00 ± 0.21%). After one week's withdrawal, the liver injury caused by the high dose of WG-r significantly recovered, while the liver damage caused by G-r was more difficult to recover. In metabolomics analysis, 14 metabolites were identified as the potential biomarkers in realgar-treated rats. These metabolites indicated that there were perturbations of the primary bile acid biosynthesis, arachidonic acid metabolism, linoleic acid metabolism, and glycerophospholipid metabolism in the realgar-treated groups. Conclusions. These results illustrate that, as a TCM processing method, water grinding had the effect of reducing toxicity, and the metabolomics method may be a valuable tool for studying the toxicity induced by TCM and the mechanism of TCM processing.

scholarly journals Lomatogonium Rotatum for Treatment of Acute Liver Injury in Mice: A Metabolomics Study

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 227 ◽  
Author(s):  
Renhao Chen ◽  
Qi Wang ◽  
Lanjun Zhao ◽  
Shilin Yang ◽  
Zhifeng Li ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Liver Injury ◽  
Acid Metabolism ◽  
Acute Liver Injury ◽  
Tca Cycle ◽  
Arachidonic Acid Metabolism ◽  
Hepatoprotective Effect ◽  
Metabolomics Study ◽  
Metabolomics Analysis

Lomatogonium rotatum (L.) Fries ex Nym (LR) is used as a traditional Mongolian medicine to treat liver and bile diseases. This study aimed to investigate the hepatoprotective effect of LR on mice with CCl4-induced acute liver injury through conventional assays and metabolomics analysis. This study consisted of male mice (n = 23) in four groups (i.e., control, model, positive control, and LR). The extract of whole plant of LR was used to treat mice in the LR group. Biochemical and histological assays (i.e., serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and histological changes of liver tissue) were used to evaluate LR efficacy, and metabolomics analysis based on GC-MS and LC-MS was conducted to reveal metabolic changes. The conventional analysis and metabolomic profiles both suggested that LR treatment could protect mice against CCl4-induced acute liver injury. The affected metabolic pathways included linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, CoA biosynthesis, glycerophospholipid metabolism, the TCA cycle, and purine metabolism. This study identified eight metabolites, including phosphopantothenic acid, succinic acid, AMP, choline, glycerol 3-phosphate, linoleic acid, arachidonic acid, and DHA, as potential biomarkers for evaluating hepatoprotective effect of LR. This metabolomics study may shed light on possible mechanisms of hepatoprotective effect of LR.

scholarly journals Systemic Elucidate The Potential Bioactive Compounds and Hypoglycemic Mechanism of Polygonum Multiflorum Based on Network Pharmacology

2020 ◽  
Author(s):  
Yunfei Song ◽  
Jianbo Yang ◽  
Wenguang Jing ◽  
Qi Wang ◽  
Yue Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bioactive Compounds ◽  
Acid Metabolism ◽  
Osteoclast Differentiation ◽  
Interaction Network ◽  
Arachidonic Acid Metabolism ◽  
Hypoglycemic Effect ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Polygonum Multiflorum

Abstract Background: Diabetes is a complex metabolic disease characterized by hyperglycemia, plaguing the whole world. However, the action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of diabetes mellitus. According to the previous research, the TCM of polygonum multiflorum (PM) showed noteworthy hypoglycemic effect. Up to now, its hypoglycemic active ingredients and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum (PM).Methods: First, the compounds with good pharmacokinetic properties were screened from the self-established library of PM, and the targets of these compounds were predicted and collected through database. Relevant targets of diabetes were summarized by searching database. The intersection targets of compound-targets and disease-targets were obtained soon. Secondly, the interaction net between the compounds and the filtered targets was established. These key targets were enriched and analyzed by PPI analysis, molecular docking verification. Finally, the key genes were used to find the biologic pathway and explain the therapeutic mechanism by GO and KEGG analysis. Results: In this study, 29 hypoglycemic components and 63 hypoglycemic targets of PM were filtrated based on online network database. Then the component-target interaction network was constructed and five key components resveratrol, apigenin, kaempferol, quercetin and luteolin were further obtained. Sequential studies turned out, AKT1, EGFR, ESR1, PTGS2, MMP9, MAPK14, and KDR were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. There were 38 metabolic pathways, including regulation of lipolysis in adipocytes, prolactin signaling pathway, TNF signaling pathway, VEGF signaling pathway, FoxO signaling pathway, estrogen signaling pathway, linoleic acid metabolism, Rap1 signaling pathway, arachidonic acid metabolism, and osteoclast differentiation closely connected with the hypoglycemic mechanism of PM.Conclusion: In summary, the study used systems pharmacology to elucidate the main hypoglycemic components and mechanism of PM. The work provided a scientific basis for the further hypoglycemic effect research of PM and its monomer components, but also provided a reference for the secondary development of PM.

scholarly journals Metabolic and Network Pharmacological Analyses of the Therapeutic Effect of Grona styracifolia on Calcium Oxalate-Induced Renal Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Chen ◽  
Yachen Si ◽  
Jin Cheng ◽  
Jiarong Ding ◽  
Hongxia Zhao ◽  
...  
Keyword(s):  
Calcium Oxalate ◽  
Therapeutic Effect ◽  
Renal Injury ◽  
High Performance ◽  
Folk Medicine ◽  
Network Pharmacology ◽  
Control Group ◽  
Protective Effects ◽  
Crystal Deposition ◽  
Flight Mass Spectrometry

Grona styracifolia (Osbeck) Merr. (GS), a popular folk medicine, is clinically applied to treat nephrolithiasis. In this study, a urinary metabolic analysis was performed in a mouse model of renal calcium oxalate (CaOx) crystal deposition to identify the differentially altered metabolites in mice with oxalate-induced renal injury and explore the therapeutic mechanisms of GS against nephrolithiasis. Twenty-four mice were randomly divided into the control, oxalate and GS-treated groups. A metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to analyze the metabolic profiles of the urine samples. In addition, network pharmacology analysis was performed with different databases. As a result, the protective effects of GS were verified by measuring biochemical parameters and detecting crystal deposition. Fifteen metabolites were identified as the differentially altered metabolites in mice with crystal-induced renal injury. Most were involved in amino acid and fatty acid metabolism. Thirteen of these metabolites showed a reversal trend following GS treatment. A component-target-metabolite network was further constructed and nine overlapping target proteins of GS and the differentially altered metabolites were discovered. Among these proteins, the expression of estrogen receptor 2 (ESR2) in renal tissues was significantly down-regulated while androgen receptor (AR) expression was obviously increased in the oxalate group compared with the control group. These changes were reversed by the GS treatment. In conclusion, GS exerts its therapeutic effect by regulating multiple metabolic pathways and the expression of ESR and AR in mice with oxalate-induced renal injury.

scholarly journals Systemic elucidation on the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum based on network pharmacology

2020 ◽  
Author(s):  
Yunfei Song ◽  
Jianbo Yang ◽  
Wenguang Jing ◽  
Qi Wang ◽  
Yue Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bioactive Compounds ◽  
Acid Metabolism ◽  
Osteoclast Differentiation ◽  
Interaction Network ◽  
Arachidonic Acid Metabolism ◽  
Hypoglycemic Effect ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Polygonum Multiflorum

Abstract Background: Diabetes is a complex metabolic disease characterized by hyperglycemia, plaguing the whole world. However, the action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of diabetes mellitus. According to the previous research, the TCM of polygonum multiflorum (PM) showed noteworthy hypoglycemic effect. Up to now, its hypoglycemic active ingredients and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum (PM).Methods: First, the compounds with good pharmacokinetic properties were screened from the self-established library of PM, and the targets of these compounds were predicted and collected through database. Relevant targets of diabetes were summarized by searching database. The intersection targets of compound-targets and disease-targets were obtained soon. Secondly, the interaction net between the compounds and the filtered targets was established. These key targets were enriched and analyzed by PPI analysis, molecular docking verification. Thirdly, the key genes were used to find the biologic pathway and explain the therapeutic mechanism by GO and KEGG analysis. Lastly, the part of potential bioactive compounds were under enzyme activity inhibition tests.Results: In this study, 29 hypoglycemic components and 63 hypoglycemic targets of PM were filtrated based on online network database. Then the component-target interaction network was constructed and five key components resveratrol, apigenin, kaempferol, quercetin and luteolin were further obtained. Sequential studies turned out, AKT1, EGFR, ESR1, PTGS2, MMP9, MAPK14, and KDR were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. There were 38 metabolic pathways, including regulation of lipolysis in adipocytes, prolactin signaling pathway, TNF signaling pathway, VEGF signaling pathway, FoxO signaling pathway, estrogen signaling pathway, linoleic acid metabolism, Rap1 signaling pathway, arachidonic acid metabolism, and osteoclast differentiation closely connected with the hypoglycemic mechanism of PM.Conclusion: In summary, the study used systems pharmacology to elucidate the main hypoglycemic components and mechanism of PM. The work provided a scientific basis for the further hypoglycemic effect research of PM and its monomer components, but also provided a reference for the secondary development of PM.

scholarly journals Maresin1 Alleviates Metabolic Dysfunction in Septic Mice: A 1H NMR-Based Metabolomics Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Hao ◽  
Hong Zheng ◽  
Ruo-Han Wang ◽  
Hui Li ◽  
Li-Li Yang ◽  
...  
Keyword(s):  
Acid Metabolism ◽  
Cecal Ligation ◽  
Mitochondrial Damage ◽  
Lipid Mediator ◽  
Protective Effects ◽  
Metabolic Dysfunction ◽  
H Nmr ◽  
Liver Injuries ◽  
The Impact ◽  
Metabolomics Analysis

Maresin1 (MaR1), a new anti-inflammatory and proresolving lipid mediator, has been proven to exert organ-protective effects in septic animal models. However, the potential mechanisms are still not fully elucidated. In this study, we sought to explore the impact of MaR1 on metabolic dysfunction in cecal ligation and puncture- (CLP-) induced septic mice. We found that MaR1 significantly increased the overall survival rate and attenuated lung and liver injuries in septic mice. In addition, MaR1 markedly reduced the levels of proinflammatory cytokines (TNF-α and IL-6) and alleviated mitochondrial damage. Based on a 1H NMR-based metabolomics analysis, CLP-induced septic mice had increased levels of acetate, pyruvate, and lactate in serum and decreased levels of alanine, aspartate, glutamate, and fumarate in lungs. However, these metabolic disorders, mainly involving energy and amino acid metabolism, can be recovered by MaR1 treatment. Therefore, our results suggest that the protective effects of MaR1 on sepsis could be related to the recovery of metabolic dysfunction and the alleviation of inflammation and mitochondrial damage.

scholarly journals Discovery of potential therapeutic targets for non-small cell lung cancer using high-throughput metabolomics analysis based on liquid chromatography coupled with tandem mass spectrometry

RSC Advances ◽  
2019 ◽  
Vol 9 (19) ◽  
pp. 10905-10913 ◽  
Author(s):  
Hong-dan Xu ◽  
Wen Luo ◽  
Yuanlong Lin ◽  
Jiawen Zhang ◽  
Lijuan Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
High Throughput ◽  
Cell Lung Cancer ◽  
Therapeutic Targets ◽  
Small Cell ◽  
Tandem Mass ◽  
Small Cell Lung ◽  
Metabolomics Analysis

High-throughput metabolomics can discover potential therapeutic targets for non-small cell lung cancer.

scholarly journals Region-Specific Biomarkers and Their Mechanisms in the Treatment of Lung Adenocarcinoma: A Study of Panax quinquefolius from Wendeng, China

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6829
Author(s):  
Xuanming Zhang ◽  
Liwen Han ◽  
Peihai Li ◽  
Shanshan Zhang ◽  
Mengqi Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Panax Quinquefolius ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Chemical Characteristics ◽  
Functional Activities ◽  
Ginsenoside Rc ◽  
Cancer Suppression ◽  
Metabolomics Analysis

Panax quinquefolius, a popular medicinal herb, has been cultivated in China for many years. In this work, the region-specific profiles of metabolites in P. quinquefolius from Wendeng was investigated using liquid-chromatography–quadrupole–time-of-flight-(LC–Q–TOF)-based metabolomics analysis. The three most abundant biomarkers, identified as ginsenoside Rb3, notoginsenoside R1, and ginsenoside Rc, were the representative chemical components employed in the network pharmacology analysis. In addition, molecular docking and western blotting analyses revealed that the three compounds were effective binding ligands with Hsp90α, resulting in the inactivation of SRC and PI3K kinase, which eventually led to the inactivation of the Akt and ERK pathways and lung cancer suppression. The outcomes obtained herein demonstrated the intriguing chemical characteristics and potential functional activities of P. quinquefolius from Wendeng.

scholarly journals Systemic elucidate the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum based on network pharmacology

2020 ◽  
Author(s):  
Yunfei Song ◽  
Jianbo Yang ◽  
Wenguang Jing ◽  
Qi Wang ◽  
Yue Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bioactive Compounds ◽  
Acid Metabolism ◽  
Osteoclast Differentiation ◽  
Interaction Network ◽  
Arachidonic Acid Metabolism ◽  
Hypoglycemic Effect ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Polygonum Multiflorum

Abstract Background: Diabetes is a complex metabolic disease characterized by hyperglycemia, plaguing the whole world. However, the action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of diabetes mellitus. According to the previous research, the TCM of polygonum multiflorum (PM) showed noteworthy hypoglycemic effect. Up to now, its hypoglycemic active ingredients and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum (PM).Methods: First, the compounds with good pharmacokinetic properties were screened from the self-established library of PM, and the targets of these compounds were predicted and collected through database. Relevant targets of diabetes were summarized by searching database. The intersection targets of compound-targets and disease-targets were obtained soon. Secondly, the interaction net between the compounds and the filtered targets was established. These key targets were enriched and analyzed by PPI analysis, molecular docking verification. Finally, the key genes were used to find the biologic pathway and explain the therapeutic mechanism by GO and KEGG analysis. Results: In this study, 29 hypoglycemic components and 63 hypoglycemic targets of PM were filtrated based on online network database. Then the component-target interaction network was constructed and five key components resveratrol, apigenin, kaempferol, quercetin and luteolin were further obtained. Sequential studies turned out, AKT1, EGFR, ESR1, PTGS2, MMP9, MAPK14, and KDR were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. There were 38 metabolic pathways, including regulation of lipolysis in adipocytes, prolactin signaling pathway, TNF signaling pathway, VEGF signaling pathway, FoxO signaling pathway, estrogen signaling pathway, linoleic acid metabolism, Rap1 signaling pathway, arachidonic acid metabolism, and osteoclast differentiation closely connected with the hypoglycemic mechanism of PM.Conclusion: In summary, the study used systems pharmacology to elucidate the main hypoglycemic components and mechanism of PM. The work provided a scientific basis for the further hypoglycemic effect research of PM and its monomer components, but also provided a reference for the secondary development of PM.

scholarly journals An Integrative Metabolomic and Network Pharmacology Study Revealing the Regulating Properties of Xihuang Pill That Improves Anlotinib Effects in Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chunyu Li ◽  
Zhihong Wang ◽  
Wei Chen ◽  
Bo Cao ◽  
Mingyu Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Acid Metabolism ◽  
Interaction Network ◽  
Complementary Therapy ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Untargeted Metabolomics ◽  
Network Pharmacology ◽  
Active Components

Lung cancer ranks as a leading cause of death. Although targeted therapies usually trigger profound initial patient responses, these effects are transient due to drug resistance and severe side effects. Xihuang Pill (XHW) is a popular Chinese medicine formula that might benefit cancer patients when used as a complementary therapy. However, its underlying mechanism when combined with anticancer drugs is not clearly understood. Here, we used an integrated strategy to reveal the regulatory properties of XHW in increasing the antitumor activity of anlotinib in lung cancer. We evaluated the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung carcinoma (LLC). We applied untargeted metabolomics to identify the differences metabolism and found that XHW improved the effects of anlotinib on lung cancer. The components and targets related to the effects of XHW treatment on lung cancer were obtained through network pharmacology. Then, by integrating the biologically active components of XHW and anlotinib as well as the treatment-responsive metabolites and their related targets, an interaction network was constructed to evaluate the combination therapy. Finally, important protein candidates for this response were verified by immunohistochemistry of tumor tissues. The results showed that XHW significantly improved the inhibitory effect of anlotinib on tumor growth in LLC-bearing mice. Additionally, 12 differentially-abundant metabolites were identified by untargeted metabolomics in the XHW/anlotinib group compared with the XHW or anlotinib groups, and they were mainly enriched in fatty acid metabolism, lipid metabolism and amino acid metabolism pathways. Anlotinib, 23 components in Shexiang, 2 components in Niuhuang, 30 components in Ruxiang and 60 components in Moyao work together to act on 30 targets to regulate hexadecanoic acid (also named palmitic acid), linoleic acid, lactosylceramide, adrenaline, arachidonic acid and lysoPC(18:1(9Z)). The results of immunohistochemistry showed that XHW combined with anlotinib reduced the expression of PDGFRA in tumors. Overall, the key metabolites of XHW that enhances the efficacy of anlotinib were regulated by a multicomponent and multitarget interaction network. Our results suggested that anlotinib combined with XHW may be a promising strategy for the treatment of lung cancer.

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