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Article ; Online: Network pharmacology and experimental validation to investigate the mechanism of Nao-Ling-Su capsule in the treatment of ischemia/reperfusion-induced acute kidney injury.

Lin, Yongqiang / Xu, Lili / Lin, Huibin / Cui, Weiliang / Jiao, Yang / Wang, Bing / Li, Huifen / Wang, Xiaojie / Wu, Jichao

Journal of ethnopharmacology

2024 Volume 326, Page(s) 117958

Abstract: Ethnopharmacological relevance: Nao-Ling-Su Capsule (NLSC) is a traditional prescription, which is ...

Abstract	Ethnopharmacological relevance: Nao-Ling-Su Capsule (NLSC) is a traditional prescription, which is composed of fifteen herbs such as epimedium, Polygala tenuifolia, and Schisandra chinensis. It has the effect of strengthening the brain, calming nerves, and protecting the kidney, which has been used clinically for many years to strengthen the brain and kidney. However, the effect of NLSC in the treatment of acute kidney injury (AKI) is still unclear. Aim of the study: The present study aims to elucidate the pharmacological actions of NLSC in the treatment of AKI. Materials and methods: Molecular targets for NLSC and AKI were obtained from various databases, and then we built networks of interactions between proteins (PPI) by employing string databases. Additionally, we employed the DAVID database to conduct gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was conducted to analyze the interaction between core components and their corresponding core targets. Next, the C57BL male mice model of ischemia/reperfusion damage (IRI) was developed, and the nephridial protective effect of NLSC was evaluated. The accuracy of the expected targets was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR). The renal protective effect of NLSC was assessed using an immortalized human kidney tubular (HK-2) cell culture produced by oxygen-glucose deprivation (OGD). Results: Network pharmacology analysis identified 199 common targets from NLSC and AKI. STAT3, HSP90AA1, TP53, MAPK3, JUN, JAK2, and VEGFA could serve as potential drug targets and were associated with JAK2/STAT3 signaling pathway, PI3K-Akt signaling pathway, etc. The molecular docking analysis confirmed significant docking activity between the main bioactive components and core targets, including STAT3 and KIM-1. Moreover, the AKI mice model was successfully established and NLSC pretreatment could improve renal function and alleviate renal damage. NLSC could alleviate renal inflammation and tubular cell apoptosis, and decrease the expression of STAT3 and KIM-1 in AKI mice. In vitro, both NLSC and drug-containing serum may protect HK-2 cells by inhibiting STAT3 signaling, especially STAT3-mediated apoptosis and KIM-1 expression. Conclusion: NLSC could alleviate renal inflammation and apoptosis, exerting its beneficial effects by targeting the STAT3/KIM-1 pathway. NLSC is a promising candidate for AKI treatment and provides a new idea and method for the treatment of AKI.
MeSH term(s)	Humans ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Kidney ; Acute Kidney Injury/drug therapy ; Reperfusion Injury/drug therapy ; Ischemia ; Reperfusion ; Nephritis ; Inflammation ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Drugs, Chinese Herbal
Language	English
Publishing date	2024-02-22
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2024.117958
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Article: Identification of naturally occurring inhibitors in Xian-Ling-Gu-Bao capsule against the glucuronidation of estrogens.

He, Liangliang / Xu, Chunxia / Wang, Ziying / Duan, Shuyi / Xu, Jinjin / Li, Chuan / Yao, Xinsheng / Gonzalez, Frank J / Qin, Zifei / Yao, Zhihong

Frontiers in pharmacology

2022 Volume 13, Page(s) 935685

Abstract: Xian-Ling-Gu-Bao (XLGB) capsule, a well-known traditional Chinese medicine prescription, is widely ...

Abstract	Xian-Ling-Gu-Bao (XLGB) capsule, a well-known traditional Chinese medicine prescription, is widely used for the treatment of osteoporosis. It could significantly increase the levels of estrogen in ovariectomized rats and mice. However, this working mechanism has not been well elucidated. Considering that UDP-glucuronosyltransferase (UGT) enzymes are the important enzymes that inactivate and regulate estrogen activity
Language	English
Publishing date	2022-08-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.935685
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Article: Qing-Kai-Ling Injection Induces Immediate Hypersensitivity Reaction

Gao, Yuan / Qi, Ruijuan / Zhang, Xiaoyu / Xu, Xudong / Han, Yixin / Fei, Qiaoling / Wang, Xiaojing / Cai, Runlan / Sun, Guibo / Qi, Yun

Frontiers in pharmacology

2020 Volume 10, Page(s) 1524

Abstract: Background and Objective: ...

Abstract	Background and Objective:
Language	English
Publishing date	2020-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2019.01524
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Article ; Online: A new strategy for discovering effective substances and mechanisms of traditional Chinese medicine based on standardized drug containing plasma and the absorbed ingredients composition, a case study of Xian-Ling-Gu-Bao capsules.

Qiu, Zuo-Cheng / Tang, Xi-Yang / Wu, Qing-Chang / Tang, Zi-Ling / Wong, Man-Sau / Chen, Jia-Xu / Yao, Xin-Sheng / Dai, Yi

Journal of ethnopharmacology

2021 Volume 279, Page(s) 114396

Abstract: ... that underlie the functions of the famous TCMF: Xian-Ling-Gu-Bao (XLGB) capsule on bone metabolism in vivo and ...

Abstract	Ethnopharmacological relevance: The overall therapeutic effect of traditional Chinese medicine formulae (TCMF) was achieved by the interactions of multiple components with multiple targets. However, current pharmacology research strategies have struggled to identify effective substance groups and encountered challenges in elucidating the underlying mechanisms of TCMF. Aim: In this study, a comprehensive strategy was proposed and applied to elucidate the interactions of the multiple components that underlie the functions of the famous TCMF: Xian-Ling-Gu-Bao (XLGB) capsule on bone metabolism in vivo and to elucidate the molecular mechanisms underlying the effects of XLGB on bone cells, especially on osteoblasts. Methods: The efficacy of XLGB in the protection against bones loss in ovariectomized (OVX) rats was confirmed by Micro-CT analysis. The anti-osteoporosis mechanism involved in the systemic regulatory actions of XLGB was elucidated by transcriptome sequencing analysis on bone marrow mesenchymal stem cells isolated from OVX rats. Moreover, the components absorbed in XLGB-treated plasma were characterized by mass spectrometry analysis, and subsequently, a standardized preparation process of drug-containing plasma was established. The synergistic osteogenic effect of the multiple components in plasma was investigated by a combination and then knockout of components using pre-osteoblast MC3T3-E1 cells. In order to decipher the underlying mechanism of XLGB, the targets of the absorbed components on bone were predicted by target prediction and network pharmacology analysis, then several interactions were validated by biochemical and cell-based assay. Results: A total of 18 genes, including HDC, CXCL1/2, TNF, IL6 and Il1b, were newly found to be the major target genes regulated by XLGB. Interestingly, we found that a combination of the three absorbed components, i.e. MSP, rather than their single form at the same concentration, stimulated the formation of calcified nodules in MC3T3-E1 cells, suggesting a synergistic effect of these components. Besides, target prediction and experimental validation confirmed the binding affinity of corylin and icaritin for estrogen receptor α and β, the inhibitory activity of isobavachin and isobavachalcone on glycogen synthase kinase-3β, and the inhibitory activity of isobavachalcone on cathepsin K. The cell-based assay further confirmed the result of the biochemical assay. A network that integrated absorbed components of XLGB-targets-perturbation genes-pathways against osteoporosis was established. Conclusion: Our current study provides a new systemic strategy for discovering active ingredient groups of TCM formulae and understanding their underlying mechanisms.
MeSH term(s)	3T3 Cells ; Administration, Oral ; Animals ; Bone Density/drug effects ; Bone Marrow Cells ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Drugs, Chinese Herbal/therapeutic use ; Estradiol/pharmacology ; Female ; Gene Expression Regulation/drug effects ; Gene Regulatory Networks ; Medicine, Chinese Traditional ; Mice ; Osteoblasts/drug effects ; Osteoblasts/physiology ; Osteoporosis/prevention & control ; Ovariectomy ; RANK Ligand/pharmacology ; RAW 264.7 Cells ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Stem Cells
Chemical Substances	Drugs, Chinese Herbal ; RANK Ligand ; Tnfsf11 protein, mouse ; xian ling gu bao ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2021-07-08
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2021.114396
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Article ; Online: Potentiation of flutamide-induced hepatotoxicity in mice by Xian-Ling-Gu-Bao through induction of CYP1A2.

Ding, Yannan / Ma, Honghong / Xu, Yasha / Yang, Feng / Li, Yi / Shi, Fuguo / Lu, Yuanfu

Journal of ethnopharmacology

2021 Volume 278, Page(s) 114299

Abstract: Ethnopharmacological relevance: Xian-Ling-Gu-Bao (XLGB) Fufang is herbal formula widely used ...

Abstract	Ethnopharmacological relevance: Xian-Ling-Gu-Bao (XLGB) Fufang is herbal formula widely used to treat osteoporosis and other bone disorders. Because of its commonality in the clinical use, there is a safety concern over the use of XLGB combined with other androgen deprivation therapy (ADT) drugs such as flutamide (FLU) that is associated with reduced bone density. To date, there have been no evaluations on the side effects of the drug-drug interaction between XLGB and FLU. Aim of the study: The present study was designed to investigate the hepatotoxicity in the context of the combined treatment of XLGB and FLU in a mouse model, and to determine whether the metabolic activation of FLU through induction of CYP1A2 plays a role in the increased hepatoxicity caused by the combination of XLGB and FLU. Materials and methods: C57 mice were administered with either XLGB (6,160 mg/kg), FLU (300 mg/kg), or with the combination of the two drugs. Animals were treated with XLGB for 5 days before the combined administration of XLGB and FLU for another 4 days. The serum of mice from single or the combined administration groups was collected for biochemical analysis. The mouse liver was collected to examine liver morphological changes, evaluate liver coefficient, as well as determine the mRNA expression of P450 isozymes (Cyp1a2, Cyp3a11 and Cyp2c37). For metabolism analysis, mice were treated with XLGB, FLU, or the combination of XLGB and FLU for 24 h. The urine samples were collected for the analysis of FLU-NAC conjugate by UPLC-Q-Orbitrap MS. The liver microsomes were prepared from fresh livers to determine the activity of metabolizing enzyme CYP1A2. Results: The combined treatment of XLGB and FLU caused loss of mice body weight and elicited significant liver toxicity as evidenced by an increased liver coefficient and serum lactate dehydrogenase (LDH) activity as well as pathological changes of fatty lesion of liver tissue. FLU increased hepatic expression of Cyp1a2 mRNA that was further elevated in the liver of mice when administered with both FLU and XLGB. Treatment of FLU resulted in an increase in the expression of Cyp3a11 mRNA that was negated when mice were co-treated with FLU and XLGB. No significant difference in Cyp2c37 mRNA expression was observed among the different treatment groups as compared to the control. Analysis of metabolic activity showed that the combined administration caused a synergic effect in elevating the activity of the CYP1A2 enzyme. Mass spectrometry analysis identified the presence of FLU reactive metabolite derived FLU-NAC conjugate in the urine of mice treated with FLU. Strikingly, about a two-fold increase of the FLU-NAC conjugate was detected when treated with both FLU and XLGB, indicating an elevated amount of toxic metabolite produced from FLU in the present of XLGB. Conclusion: FLU and XLGB co-treatment potentiated FLU-induced hepatoxicity. This increased hepatoxicity was mediated through the induction of CYP1A2 activity which in turn enhanced bioactivation of FLU leading to over production of FLU-NAC conjugate and oxidative stress. These results offer warnings about serious side effects of the FLU-XLGB interaction in the clinical practice.
MeSH term(s)	Androgen Antagonists/administration & dosage ; Androgen Antagonists/toxicity ; Animals ; Chemical and Drug Induced Liver Injury/pathology ; Cytochrome P-450 CYP1A2/genetics ; Cytochrome P-450 CYP1A2/metabolism ; Drug Synergism ; Drug Therapy, Combination ; Drugs, Chinese Herbal/administration & dosage ; Drugs, Chinese Herbal/toxicity ; Flutamide/administration & dosage ; Flutamide/chemistry ; Flutamide/toxicity ; Gene Expression Regulation, Enzymologic/drug effects ; Mice ; Molecular Structure ; Phytotherapy/adverse effects
Chemical Substances	Androgen Antagonists ; Drugs, Chinese Herbal ; xian ling gu bao ; Flutamide (76W6J0943E) ; Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; cytochrome P-450 1A2, mouse (EC 1.14.14.1)
Language	English
Publishing date	2021-06-04
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2021.114299
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Article ; Online: Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine.

Dang, Yanqi / Xu, Jingjuan / Yang, Yang / Li, Chunlin / Zhang, Qiang / Zhou, Wenjun / Zhang, Li / Ji, Guang

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2020 Volume 127, Page(s) 109976

Abstract: Background: The ling-gui-zhu-gan (LGZG) decoction is a classic formula ...

Abstract	Background: The ling-gui-zhu-gan (LGZG) decoction is a classic formula in traditional chinese medicine (TCM) and is widely used in clinical settings. Recently, the LGZG decoction was demonstrated to have an effect in alleviating hepatic steatosis induced by a high-fat diet (HFD). However, the mechanisms underlying this therapeutic effect remain unclear. The present study was designed to evaluate the effect and explore possible mechanisms of action of the LGZG decoction in nonalcoholic fatty liver disease (NAFLD). Methods: Liver tissue and blood samples were harvested. Liver steatosis, triglyceride (TG), liver total cholesterol (TC), liver low-density lipoprotein (LDL), serum almandine aminotransferase (ALT), aspartate aminotransferase (AST), and free fatty acid (FFA) were assayed. N6-methyladenosine (m6A) levels were estimated using an m6A RNA methylation quantification kit and immunohistochemistry. The m6A methylome was detected through methylated RNA immunoprecipitation sequencing (MeRIP-seq), followed by data analysis. The expression levels of differentially methylated genes (DMGs) were determined using real-time polymerase chain reaction and western blotting. Results: The LGZG decoction significantly alleviated hepatic steatosis and reduced m6A levels. MeRIP-seq revealed the coding sequence (CDS) domain to be the most critical modification site for m6A methylation, and the molecular functions of DMGs predominantly included insulin-like growth factor receptor binding and fatty acid metabolism and degradation. Further, LGZG treatment could reduce the m6A methylation levels of suppressor of cytokine signaling 2 (SOCS2), along with the expression of SOCS2 at mRNA and protein levels. Conclusions: The LGZG decoction is an effective formula for treating NAFLD, and the possible mechanisms underlying its action could be related to N6-methyladenosine modification-medicated SOCS2.
MeSH term(s)	Adenosine/analogs & derivatives ; Adenosine/metabolism ; Animals ; Cholesterol/metabolism ; DNA Methylation/drug effects ; Diet, High-Fat/adverse effects ; Fatty Acids, Nonesterified/blood ; Fatty Acids, Nonesterified/metabolism ; Fatty Liver/prevention & control ; Liver/metabolism ; Male ; Methylation/drug effects ; Plant Extracts/pharmacology ; Rats ; Suppressor of Cytokine Signaling Proteins/biosynthesis ; Transaminases/blood ; Transaminases/metabolism
Chemical Substances	Fatty Acids, Nonesterified ; Plant Extracts ; Socs2 protein, rat ; Suppressor of Cytokine Signaling Proteins ; ling-gui-zhu-gan decoction ; Cholesterol (97C5T2UQ7J) ; N-methyladenosine (CLE6G00625) ; Transaminases (EC 2.6.1.-) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2020-05-20
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2020.109976
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Article ; Online: Gan-Jiang-Ling-Zhu decoction alleviates hepatic steatosis in rats by the miR-138-5p/CPT1B axis.

Dang, Yanqi / Xu, Jingjuan / Zhu, Mingzhe / Zhou, Wenjun / Zhang, Li / Ji, Guang

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2020 Volume 127, Page(s) 110127

Abstract: ... liver disease which lacks verified pharmacological interventions. Gan-Jiang-Ling-Zhu decoction (GJLZ) is ...

Abstract	Background: Non-alcoholic fatty liver disease (NAFLD) is a commonly-encountered chronic liver disease which lacks verified pharmacological interventions. Gan-Jiang-Ling-Zhu decoction (GJLZ) is a classic formula utilized in clinical practice. In this study, we aimed to evaluate the therapeutic effect of GJLZ in NAFLD and explore the possible underlying mechanisms. Methods: Twenty-four rats were randomly divided into three groups: normal group, fed with chow diet for 8 weeks; model group, fed with high fat diet for 8 weeks; and GJLZ group, initially fed HFD for 4 weeks, and then administered the GJLZ decoction for 4 weeks by oral gavage while continuously feeding HFD. Rats were sacrificed after the intervention, and liver tissues and blood samples were harvested. Liver steatosis was detected by HE and Oil Red O staining. Body weight and liver index were analyzed. Liver triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), serum almandine aminotransferase (ALT), aspartate aminotransferase (AST), and nonesterified fatty acid (NEFA) were assayed using commercial kits. Differentially expressed genes were identified by RNA-sequencing and verified using real-time PCR (RT-PCR) and western blotting. Whole miRNAs were detected by RNA-sequence analysis, and mRNA-targeted miRNAs were verified by RT-PCR. The miRNA-mRNA regulation pattern was confirmed using the dual-luciferase reporter assay. Results: Treatment with GJLZ significantly improved hepatic steatosis and inflammation, reduced liver index and liver TG content, and also significantly reduced serum ALT and AST levels. Based on the results of RNA-sequence analysis, five differentially expressed genes (DEGs) in the peroxisome proliferator-activated receptor (PPAR) signaling pathway were recognized. RT-PCR confirmed that carnitine palmitoyltransferase 1b (CPT1B) expression was significantly regulated by GJLZ treatment. GJLZ decoction intervention also increased significantly hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA) expression. Next, miRNA profiling and screening were performed based on CPT1B alteration. Rno-miR-138-5p likely responded to GJLZ intervention, and rno-miR-138-5p inhibitor increased CPT1B expression while rno-miR-138-5p mimic reduced CPT1B expression. When CPT1B mutated, miR-138-5p mimic and inhibitor could not regulate the luciferase activity of CPT1B. Conclusions: GJLZ is an effective formula for NAFLD management, and its possible mechanism of action involves the regulation of CPT1B expression via rno-miR-138-5p.
MeSH term(s)	Animals ; Carnitine O-Palmitoyltransferase/genetics ; Carnitine O-Palmitoyltransferase/physiology ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Fatty Acids/metabolism ; Gene Expression Regulation/drug effects ; Liver/metabolism ; Male ; Medicine, Chinese Traditional ; MicroRNAs/physiology ; Non-alcoholic Fatty Liver Disease/drug therapy ; Non-alcoholic Fatty Liver Disease/metabolism ; Peroxisome Proliferator-Activated Receptors/physiology ; Rats ; Rats, Wistar ; Triglycerides/metabolism
Chemical Substances	Drugs, Chinese Herbal ; Fatty Acids ; MIRN138 microRNA, rat ; MicroRNAs ; Peroxisome Proliferator-Activated Receptors ; Triglycerides ; CPT1b protein, rat (EC 2.3.1.21) ; Carnitine O-Palmitoyltransferase (EC 2.3.1.21)
Language	English
Publishing date	2020-04-20
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2020.110127
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Article: A new strategy for discovering effective substances and mechanisms of traditional Chinese medicine based on standardized drug containing plasma and the absorbed ingredients composition, a case study of Xian-Ling-Gu-Bao capsules

Qiu, Zuo-cheng / Tang, Xi-yang / Wu, Qing-chang / Tang, Zi-ling / Wong, Man-sau / Chen, Jia-xu / Yao, Xin-sheng / Dai, Yi

Journal of ethnopharmacology. 2021 Oct. 28, v. 279

2021

Abstract: ... the interactions of the multiple components that underlie the functions of the famous TCMF: Xian-Ling-Gu-Bao (XLGB ...

Abstract	The overall therapeutic effect of traditional Chinese medicine formulae (TCMF) was achieved by the interactions of multiple components with multiple targets. However, current pharmacology research strategies have struggled to identify effective substance groups and encountered challenges in elucidating the underlying mechanisms of TCMF.In this study, a comprehensive strategy was proposed and applied to elucidate the interactions of the multiple components that underlie the functions of the famous TCMF: Xian-Ling-Gu-Bao (XLGB) capsule on bone metabolism in vivo and to elucidate the molecular mechanisms underlying the effects of XLGB on bone cells, especially on osteoblasts.The efficacy of XLGB in the protection against bones loss in ovariectomized (OVX) rats was confirmed by Micro-CT analysis. The anti-osteoporosis mechanism involved in the systemic regulatory actions of XLGB was elucidated by transcriptome sequencing analysis on bone marrow mesenchymal stem cells isolated from OVX rats. Moreover, the components absorbed in XLGB-treated plasma were characterized by mass spectrometry analysis, and subsequently, a standardized preparation process of drug-containing plasma was established. The synergistic osteogenic effect of the multiple components in plasma was investigated by a combination and then knockout of components using pre-osteoblast MC3T3-E1 cells. In order to decipher the underlying mechanism of XLGB, the targets of the absorbed components on bone were predicted by target prediction and network pharmacology analysis, then several interactions were validated by biochemical and cell-based assay.A total of 18 genes, including HDC, CXCL1/2, TNF, IL6 and Il1b, were newly found to be the major target genes regulated by XLGB. Interestingly, we found that a combination of the three absorbed components, i.e. MSP, rather than their single form at the same concentration, stimulated the formation of calcified nodules in MC3T3-E1 cells, suggesting a synergistic effect of these components. Besides, target prediction and experimental validation confirmed the binding affinity of corylin and icaritin for estrogen receptor α and β, the inhibitory activity of isobavachin and isobavachalcone on glycogen synthase kinase-3β, and the inhibitory activity of isobavachalcone on cathepsin K. The cell-based assay further confirmed the result of the biochemical assay. A network that integrated absorbed components of XLGB-targets-perturbation genes-pathways against osteoporosis was established.Our current study provides a new systemic strategy for discovering active ingredient groups of TCM formulae and understanding their underlying mechanisms.
Keywords	Oriental traditional medicine ; active ingredients ; bone formation ; bone marrow ; case studies ; cathepsin K ; drugs ; estrogen receptors ; glycogen (starch) synthase ; interleukin-6 ; mass spectrometry ; micro-computed tomography ; osteoporosis ; ovariectomy ; pharmacology ; prediction ; synergism ; transcriptome
Language	English
Dates of publication	2021-1028
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2021.114396
Database	NAL-Catalogue (AGRICOLA)

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Article: A Network Pharmacology Approach to Uncover the Molecular Mechanisms of Herbal Formula Kang-Bai-Ling for Treatment of Vitiligo.

Xu, Manyuan / Shi, Jianxin / Min, Zhongsheng / Zhu, Hongliu / Sun, Weiguo

Evidence-based complementary and alternative medicine : eCAM

2019 Volume 2019, Page(s) 3053458

Abstract: Background: Kang-bai-ling (KBL), a Chinese patent medicine, has been demonstrated as an effective ...

Abstract	Background: Kang-bai-ling (KBL), a Chinese patent medicine, has been demonstrated as an effective therapy for vitiligo in China. However, the pharmacological mechanisms of KBL have not been completely elucidated. Methods: In this study, the potential multicomponent, multitarget, and multipathway mechanism of KBL against vitiligo was clarified by using network pharmacology-based strategy. In brief, potential targets of KBL were collected based on TCMSP databases, followed by network establishment concerning the interactions of potential targets of KBL with well-known therapeutic targets of vitiligo by using protein-protein interaction (PPI) data. As a result, key nodes with higher level of seven topological parameters, including "degree centrality (DC)," "betweenness centrality (BC)," "closeness centrality (CC)," "eigenvector centrality (EC)," "network centrality (NC)," and "local average connectivity (LAC)" were identified as the main targets in the network, followed by subsequent incorporation into the ClueGO for GO and KEGG signaling pathway enrichment analysis. Results: In accordance with the topological importance, a total of 23 potential targets of KBL on vitiligo were identified as main hubs. Additionally, enrichment analysis suggested that targets of KBL on vitiligo were mainly clustered into multiple biological processes (associated with DNA translation, lymphocyte differentiation and activation, steroid biosynthesis, autoimmune and systemic inflammatory reaction, neuron apoptosis, and vitamin deficiency) and related pathways (TNF, JAK-STAT, ILs, TLRs, prolactin, and NF- Conclusion: In this work, we successfully illuminated the "multicompounds, multitargets" therapeutic action of KBL on vitiligo by using network pharmacology. Moreover, our present outcomes might shed light on the further clinical application of KBL on vitiligo treatment.
Language	English
Publishing date	2019-11-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2019/3053458
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Article ; Online: Systems Pharmacology and Microbiome Dissection of Shen Ling Bai Zhu San Reveal Multiscale Treatment Strategy for IBD.

Lv, Wei-Jie / Liu, Cui / Li, Yue-Fei / Chen, Wen-Qian / Li, Zeng-Quan / Li, Yue / Xiong, Ying / Chao, Li-Min / Xu, Xiao-Long / Guo, Shi-Ning

Oxidative medicine and cellular longevity

2019 Volume 2019, Page(s) 8194804

Abstract: ... gut microbiota. Therefore, IBD therapy should be improved to utilize multiple strategies. Shen Ling ...

Abstract	Generally, inflammatory bowel disease (IBD) can be caused by psychology, genes, environment, and gut microbiota. Therefore, IBD therapy should be improved to utilize multiple strategies. Shen Ling Bai Zhu San (SLBZS) adheres to the aim of combating complex diseases from an integrative and holistic perspective, which is effective for IBD therapy. Herein, a systems pharmacology and microbiota approach was developed for these molecular mechanisms exemplified by SLBZS. First, by systematic absorption-distribution-metabolism-excretion (ADME) analysis, potential active compounds and their corresponding direct targets were retrieved. Then, the network relationships among the active compounds, targets, and disease were built to deduce the pharmacological actions of the drug. Finally, an "IBD pathway" consisting of several regulatory modules was proposed to dissect the therapeutic effects of SLBZS. In addition, the effects of SLBZS on gut microbiota were evaluated through analysis of the V3-V4 region and multivariate statistical methods. SLBZS significantly shifted the gut microbiota structure in a rat model. Taken together, we found that SLBZS has multidimensionality in the regulation of IBD-related physiological processes, which provides new sights into herbal medicine for the treatment of IBD.
MeSH term(s)	Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Microbiota
Chemical Substances	Drugs, Chinese Herbal ; shen ling bai zhu
Language	English
Publishing date	2019-06-23
Publishing country	United States
Document type	Journal Article
ISSN	1942-0994
ISSN (online)	1942-0994
DOI	10.1155/2019/8194804
Database	MEDical Literature Analysis and Retrieval System OnLINE

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