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Article ; Online: Exploring the Effect of Xiao-Chai-Hu Decoction on Treating Psoriasis Based on Network Pharmacology and Experiment Validation.

He, Ke / Wang, Ziyang / Liu, Meng / Du, Wenqian / Yin, Tingyi / Bai, Ruimin / Duan, Qiqi / Wang, Yuqian / Lei, Hao / Zheng, Yan

Current pharmaceutical design

2024 Volume 30, Issue 3, Page(s) 215–229

Abstract: Background: Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu ...

Abstract	Background: Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu Decoction (XCHD) has shown good effects against some inflammatory diseases and cancers. However, the pharmacological effect and mechanisms of XCHD on psoriasis are not yet clear. Objective: To uncover the effect and mechanisms of XCHD on psoriasis by integrating network pharmacology, molecular docking, and in vivo experiments. Methods: The active ingredients and corresponding targets of XCHD were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). Differentially expressed genes (DEGs) of psoriasis were obtained from the gene expression omnibus (GEO) database. The XCHD-psoriasis intersection targets were obtained by intersecting XCHD targets, and DEGs were used to establish the "herb-active ingredient-target" network and Protein-Protein Interaction (PPI) Network. The hub targets were identified based on the PPI network by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed next. Molecular docking was executed via AutoDockTools-1.5.6. Finally, Results: 58 active components and 219 targets of XCHD were screened. 4 top-active components (quercetin, baicalein, wogonin and kaempferol) and 7 hub targets (IL1B, CXCL8, CCND1, FOS, MMP9, STAT1 and CCL2) were identified. GO and KEGG pathway enrichment analyses indicated that the TNF signaling pathway, IL-17 signaling pathway and several pathways were involved. Molecular docking results indicated that hub genes had a good affinity to the corresponding key compounds. In imiquimod (IMQ)-induced psoriasis mouse models, XCHD could significantly improve psoriasis-like skin lesions, downregulate KRT17 and Ki67, and inhibit inflammation cytokines and VEGF. Conclusion: XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.
MeSH term(s)	Animals ; Mice ; Network Pharmacology ; Molecular Docking Simulation ; Psoriasis ; Skin ; Inflammation ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional
Chemical Substances	Drugs, Chinese Herbal
Language	English
Publishing date	2024-03-27
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/0113816128288527240108110844
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Zs.A 4714: Show issues

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Article ; Online: Inhibiting virus replication and excessive inflammatory response: Mechanism of combined prescription of Ma-Xing-Shi-Gan decoction and Xiao-Chai-Hu decoction against influenza virus.

Cheng, Miao / Zhang, Yanan / Yan, Jun / Huang, Yuanming / Wang, Mingzhe / Zhai, Zhiguang / Liu, Guoxing / Liu, Chang / Li, Jintong / Zhang, Yue / Xiao, Yuchun / Wang, Chengxiang / Ban, Chengjun / Ren, Zhihong / Song, Liqiong

Journal of ethnopharmacology

2023 Volume 313, Page(s) 116481

Abstract: ... Gan decoction with Xiao-Chai-Hu decoction), named as San-Yang-He-Zhi (SYHZ) decoction, has been widely ...

Abstract	Ethnopharmacological relevance: The combined prescription of two classical decoctions (Ma-Xing-Shi-Gan decoction with Xiao-Chai-Hu decoction), named as San-Yang-He-Zhi (SYHZ) decoction, has been widely used for the treatment of influenza virus (IFV) infections for decades. Aim of the study: This study aimed to evaluate the anti-influenza effect of SYHZ decoction and explore the underlying mechanism. Materials and methods: The ingredients of SYHZ decoction were analyzed by mass spectrometry. An animal model of IFV infection was established by challenging C57BL/6J mice with PR8 virus. Three groups of mice were infected with lethal or non-lethal doses of IFV, then followed by oral administration of phosphate-buffered saline (PBS), or SYHZ, or oseltamir; blank control mice (without IFV infection) were treated with PBS. Survival rate, Lung index, colon length, body weight loss and IFV viral load were measured 7 days post infection; histology and electron-microscopy examinations of lung tissue were performed; cytokine and chemokine levels in lung and serum were measured; and the intestinal metagenome, the cecum metabolome, and the lung transcriptome were analyzed. Results: SYHZ treatment significantly improved survival rate compared with PBS (40% vs 0%); improved lung index, colon length, and body weight loss; and alleviated lung histological damage and viral load. SYHZ-treated mice had significantly lower levels of IL-1β, TNF-α, IL-6, CCL2, CXCL10 in lung and serum, and increased levels of multiple bioactive components in cecum. Pro-inflammatory cytokines, Toll- and NOD-like receptors, pro-apoptosis molecules, and lung-injury-related proteins were downregulated in SYHZ mice, whereas surfactant protein and mucin were upregulated. The NOD-like receptor pathway, Toll-like receptor pathway, and NF-κB pathway were downregulated by SYHZ treatment. Conclusions: SYHZ decoction alleviated IFV infection in a mouse model. Multiple bioactive ingredients of SYHZ may inhibit replication of IFV and suppress excessive immune response.
MeSH term(s)	Mice ; Animals ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Lung ; Orthomyxoviridae Infections ; Cytokines/metabolism ; Orthomyxoviridae/metabolism ; Virus Replication ; Weight Loss
Chemical Substances	Drugs, Chinese Herbal ; Cytokines
Language	English
Publishing date	2023-04-16
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.2023.116481
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Zs.A 1494: Show issues

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Article ; Online: Amalgamated Pharmacoinformatics Study to Investigate the Mechanism of Xiao Jianzhong Tang against Chronic Atrophic Gastritis.

Lian, Xu / Fan, Kaidi / Qin, Xuemei / Liu, Yuetao

Current computer-aided drug design

2023

Abstract: Background: Traditional Chinese medicine (TCM) Xiaojianzhong Tang (XJZ) has a favorable efficacy in the treatment of chronic atrophic gastritis (CAG). However, its pharmacological mechanism has not been fully explained.: Objective: The purpose of ... ...

Abstract	Background: Traditional Chinese medicine (TCM) Xiaojianzhong Tang (XJZ) has a favorable efficacy in the treatment of chronic atrophic gastritis (CAG). However, its pharmacological mechanism has not been fully explained. Objective: The purpose of this study was to find the potential mechanism of XJZ in the treatment of CAG using pharmacocoinformatics approaches. Methods: Network pharmacology was used to screen out the key compounds and key targets, MODELLER and GNNRefine were used to repair and refine proteins, Autodock vina was employed to perform molecular docking, ΔLin_F9XGB was used to score the docking results, and Gromacs was used to perform molecular dynamics simulations (MD). Results: Kaempferol, licochalcone A, and naringenin, were obtained as key compounds, while AKT1, MAPK1, MAPK14, RELA, STAT1, and STAT3 were acquired as key targets. Among docking results, 12 complexes scored greater than five. They were run for 50ns MD. The free binding energy of AKT1-licochalcone A and MAPK1-licochalcone A was less than -15 kcal/mol and AKT1-naringenin and STAT3-licochalcone A was less than -9 kcal/mol. These complexes were crucial in XJZ treating CAG. Conclusion: Our findings suggest that licochalcone A could act on AKT1, MAPK1, and STAT3, and naringenin could act on AKT1 to play the potential therapeutic effect on CAG. The work also provides a powerful approach to interpreting the complex mechanism of TCM through the amalgamation of network pharmacology, deep learning-based protein refinement, molecular docking, machine learning-based binding affinity estimation, MD simulations, and MM-PBSA-based estimation of binding free energy.
Language	English
Publishing date	2023-07-20
Publishing country	United Arab Emirates
Document type	Journal Article
ISSN	1875-6697
ISSN (online)	1875-6697
DOI	10.2174/1573409919666230720141115
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Article ; Online: Xiao-Xu-Ming decoction extracts promotes mitochondrial biogenesis and improves neurobehavioral deficits in cerebral ischemia/reperfusion rats

Xiao Cheng / Ying-Lin Yang / Wei-Han Li / Man Liu / Shan-Shan Zhang / Dong-Ni Liu / Li-Da Du / Yue-Hua Wang / Guan-Hua Du

Pharmacological Research - Modern Chinese Medicine, Vol 5, Iss , Pp 100192- (2022)

2022

Abstract: ... Traditional Chinese medicine plays an important role in preventing and treatment of stroke. Xiao-Xu-Ming decoction (XXM) is ...

Abstract	Introduction: Stroke is one of the leading causes of death and disability in the worldwide. Traditional Chinese medicine plays an important role in preventing and treatment of stroke. Xiao-Xu-Ming decoction (XXM) is an effective traditional Chinese prescription for the treatment of stroke and its sequelae. Previous studies have reported the extracts of XXM has a good therapeutic effect on experimental animal stroke. However, the mechanism is unclear. Our present study focused on metabolic remodeling in cerebral ischemia-reperfusion to investigate the mechanism of XXM on cerebral ischemia/reperfusion (I/R). Methods: The cerebral I/R rat model was established by 90 min middle cerebral artery occlusion following reperfusion. XXM at doses of 37.5, 75 and 150 mg/kg was administered for the continuous 7 day after cerebral I/R. Behavioral testing, cerebral infarction detected by TTC staining, Nissl staining, NeuN immunohistochemical staining, and MAP2 immunofluorescence staining were conducted to evaluate the effect of XXM treatment on cerebral I/R of rats. TUNEL staining was used to detect DNA damage. The expression of related proteins was detected by qPCR and western blotting. Results: 7 day XXM treatment improved neurological and behavioral deficits, regulated the biogenesis and dynamic process of mitochondria, promoted the recovery of mitochondrial function, and improved the energy metabolism disorder after cerebral I/R. Furthermore, XXM also had an improving effect on mitochondrial-dependent apoptosis after cerebral I/R. Conclusion: we found that XXM regulated metabolic remodeling in cerebral ischemia-reperfusion and improve neurological deficits.
Keywords	Xiao-Xu-Ming decoction ; Cerebral Ischemia ; Metabolic remodeling ; Mitochondrial function ; Apoptosis ; Other systems of medicine ; RZ201-999 ; Therapeutics. Pharmacology ; RM1-950
Subject code	610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Hu-Qi-Zheng-Xiao Decoction Inhibits the Metastasis of Hepatocellular Carcinoma Cells by Suppressing the HIF-1α Signaling Pathway to Inhibit EMT, LCSC, and Angiogenic Process.

Wang, Xuejing / Yin, Ling / Chai, Mengyin / Kou, Buxin / Liu, Xiaoni / Wang, Xiaojun

Integrative cancer therapies

2024 Volume 23, Page(s) 15347354231226126

Abstract: ... of the digestive system. Hu-Qi-Zheng-Xiao (HQZX) decoction has been clinically found to prolong the survival of patients ...

Abstract	Background: Hepatocellular carcinoma (HCC) is a common clinical malignant tumor of the digestive system. Hu-Qi-Zheng-Xiao (HQZX) decoction has been clinically found to prolong the survival of patients with hepatocellular carcinoma and improve the quality of patients' survival, but its antitumor biological mechanism is still unclear. Methods: A nude mouse hollow fiber hepatocellular carcinoma model was constructed to analyze the in vivo efficacy of HQZX decoction against 7 different hepatocellular carcinoma cells. The subcutaneous graft tumor model was again validated. In vitro, the effect of HQZX decoction on the growth and metastasis of the cell line with the highest growth inhibition was evaluated. The cell line with the best efficacy response screened was again used to construct a hollow fiber hepatocellular carcinoma model and hollow fiber conduit cells were extracted to detect the expression of HIF-1α, VEGF, EMT-related molecules, LCSCs-related molecules, and to observe the density of the subcutaneous vascular network of hollow fiber conduits. The liver metastasis model of splenic injection was constructed to observe the effect of HQZX decoction on tumor metastasis. Results: The hollow fiber hepatocellular carcinoma model was evaluated for the efficacy of HQZX decoction, and it was found to have the highest growth inhibition of LM3-luc cells. In vitro, the CCK8 assay revealed that HQZX decoction could inhibit tumor migration and invasion and promote apoptosis. In addition, the mechanism study of extracting cells from hollow fiber tubes found that HQZX decoction could inhibit metastasis-associated HIF-1α, VEGF, EMT-related molecules, and LCSCs-related molecules expression. capillary network around subcutaneous fiber tubes was reduced in the HQZX decoction gavage group of mice. It inhibited tumor metastasis in nude mice. Conclusions: HQZX decoction inhibited the growth of a variety of hepatocellular carcinoma cells. HQZX decoction suppressed the expression of metastasis-associated VEGF, EMT-related molecules, and LCSCs-related molecules and inhibited tumor angiogenesis and growth and metastasis, which may be related to the inhibition of the HIF-1α signaling pathway. It reveals that HQZX decoction may be a promising herbal compound for anti-HCC therapy, and also reveals the accurate feasibility of the hollow fiber hepatocellular carcinoma model for in vivo pharmacodynamic evaluation and mechanism study.
MeSH term(s)	Humans ; Mice ; Animals ; Carcinoma, Hepatocellular/metabolism ; Liver Neoplasms/metabolism ; Mice, Nude ; Vascular Endothelial Growth Factor A/metabolism ; Cell Line, Tumor ; Signal Transduction ; Cell Proliferation
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2182320-0
ISSN	1552-695X ; 1534-7354
ISSN (online)	1552-695X
ISSN	1534-7354
DOI	10.1177/15347354231226126
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Zs.A 6026: Show issues

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Article: Tracheophyte of Xiao Hinggan Ling in China: an updated checklist.

Wang, Hongfeng / Dong, Xueyun / Liu, Yi / Ma, Keping

Biodiversity data journal

2019 Volume 7, Page(s) e32306

Abstract: Background: This paper presents an updated list of tracheophytes of Xiao Hinggan Ling. The list ... Containing subspecific units), 56 genera and 6 families represent first published records for Xiao Hinggan ... in our research over the past ten years.This paper presents an updated list of tracheophytes of Xiao Hinggan Ling ...

Abstract	Background: This paper presents an updated list of tracheophytes of Xiao Hinggan Ling. The list includes 124 families, 503 genera and 1640 species (Containing subspecific units), of which 569 species (Containing subspecific units), 56 genera and 6 families represent first published records for Xiao Hinggan Ling. The aim of the present study is to document an updated checklist by reviewing the existing literature, browsing the website of National Specimen Information Infrastructure and additional data obtained in our research over the past ten years.This paper presents an updated list of tracheophytes of Xiao Hinggan Ling. The list includes 124 families, 503 genera and 1640 species (Containing subspecific units), of which 569 species (Containing subspecific units), 56 genera and 6 families represent first published records for Xiao Hinggan Ling. The aim of the present study is to document an updated checklist by reviewing the existing literature, browsing the website of National Specimen Information Infrastructure and additional data obtained in our research over the past ten years. New information: This is the first complete checklist of tracheophytes of Xiao Hinggan Ling. A total of 1640 species and subspecies are listed, of which 569 species (ontaining subspecific units) represent first published records.
Language	English
Publishing date	2019-03-27
Publishing country	Bulgaria
Document type	Journal Article
ZDB-ID	2736709-5
ISSN	1314-2828
ISSN	1314-2828
DOI	10.3897/BDJ.7.e32306
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Article ; Online: Combination of chemical profiling and network pharmacology analysis to investigate the potential mechanism of Li-Zhong-Xiao-Pi granules in the treatment of gastric precancerous lesions.

Liu, Chenchen / Chen, Huiling / Zhang, Yida / Li, Meng / Jiang, Qiyao / Wang, Zhendong / Yu, Liangwen / Wang, Qi / Pan, Huafeng / Zhuo, Yue

Biomedical chromatography : BMC

2023 Volume 37, Issue 4, Page(s) e5589

Abstract: Li-Zhong-Xiao-Pi granules (LZXP) are effective for treating gastric precancerous lesions (GPL ...

Abstract	Li-Zhong-Xiao-Pi granules (LZXP) are effective for treating gastric precancerous lesions (GPL) in traditional Chinese medicine. However, the active compounds of LZXP and their potential therapeutic mechanism in GPL remained unclarified. The purpose of this study is to investigate the chemical composition and potential targets of LZXP. Based on the accurate masses, ion fragments, and literature data, a total of 128 compounds were identified in the LZXP sample using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) in both positive and negative ion modes, and 28 of these compounds were exactly determined by comparison with authentic reference standards. Meanwhile, 11 typical components were quantified via UPLC during a 24 min period. The linearity, accuracy, stability and recovery of the method were all proven. Through the network pharmacological analysis, six chemicals (quercetin, 4'-hydroxywogonin, sinensetin, 5, 7, 8, 3', 4'-pentamethoxyflavanone, 8-gingerdione and quercetin) were identified as the active ingredients, and five LZXP targets (AKT1, CYP1B1, PTGS2, MMP9 and EGFR) were found to be the crucial molecules in the treatment of GPL. This study provides a systematic and applicable method for the rapid screening and identification of the chemical constituents from LZXP, and an effective understanding the mechanism of LZXP in the treatment of GPL.
MeSH term(s)	Chromatography, High Pressure Liquid/methods ; Drugs, Chinese Herbal/chemistry ; Quercetin ; Network Pharmacology ; Mass Spectrometry/methods
Chemical Substances	Drugs, Chinese Herbal ; Quercetin (9IKM0I5T1E)
Language	English
Publishing date	2023-02-07
Publishing country	England
Document type	Journal Article
ZDB-ID	632848-9
ISSN	1099-0801 ; 0269-3879
ISSN (online)	1099-0801
ISSN	0269-3879
DOI	10.1002/bmc.5589
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Zs.A 2166: Show issues

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Article ; Online: Insight into the mechanism of Xiao-Chai-Hu-Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut β-GUS.

Wang, Caiyan / Teng, Xiaojun / Wang, Chuang / Liu, Binjie / Zhou, Runze / Xu, Xueyu / Qiu, Huawei / Fu, Yu / Sun, Rongjin / Liang, Zuhui / Zhang, Rong / Liu, Zhongqiu / Zhang, Lin / Zhu, Lijun

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 120, Page(s) 155040

Abstract: Background: Irinotecan (CPT-11, Camptosar: Purpose: Herein, Xiao-Chai-Hu-Tang (XCHT ...

Abstract	Background: Irinotecan (CPT-11, Camptosar Purpose: Herein, Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese formula, was applied to mitigate CPT-11-induced toxicity. This study initially explored the mechanism by which XCHT alleviated diarrhea, especially for β-GUS from the gut microbiota. Methods: First, we examined the levels of the proinflammatory cytokines and the anti-inflammatory cytokines in the intestine. Furthermore, we researched the community abundances of the gut microbiota in the CPT-11 and XCHT-treated mice based on 16S rRNA high-throughput sequencing technology. Meanwhile, the level of SN-38 and the concentrations of β-GUS in intestine were examined. We also resolved the 3D structure of β-GUS from gut microbiota by X-ray crystallography technology. Moreover, we used virtual screening, SPR analysis, and enzyme activity assays to confirm whether the main active ingredients from XCHT could selectively inhibit β-GUS. Results: In XCHT-treated mice, the levels of the proinflammatory cytokines decreased, the anti-inflammatory cytokines increased, and the community abundances of beneficial Firmicutes and Bacteroidota improved in the gut microbiota. We also found that the concentrations of β-GUS and the level of SN-38, the major ingredient that induces diarrhea in the gut, significantly decreased after coadministration of XCHT with CPT-11 in the intestine. Additionally, we revealed the structural differences of β-GUS from different gut microbiota. Finally, we found that EcGUS had good affinity with baicalein and meanwhile could be selectively inhibited by baicalein from XCHT. Conclusions: Overall, XCHT could relieve the delayed diarrhea induced by CPT-11 through improving the abundance of beneficial gut microbiota and reduced inflammation. Furthermore, based on the three-dimensional structure, baicalein, especially, could be used as a candidate EcGUS inhibitor to alleviate CPT-11-induced diarrhea.
MeSH term(s)	Animals ; Mice ; Glucuronidase ; Irinotecan ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Cytokines ; Diarrhea/chemically induced ; Diarrhea/drug therapy
Chemical Substances	Glucuronidase (EC 3.2.1.31) ; Irinotecan (7673326042) ; shosaiko-to ; RNA, Ribosomal, 16S ; Cytokines
Language	English
Publishing date	2023-08-19
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.155040
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Zs.A 4115: Show issues

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Article ; Online: Xiao-qing-long-tang ameliorates OVA-induced allergic rhinitis by inhibiting ILC2s through the IL-33/ST2 and JAK/STAT pathways.

Zhang, Jia-Jun / He, Xue-Cheng / Zhou, Min / Liu, Qin-Dong / Xu, Wei-Zhen / Yan, Ya-Jie / Ruan, Yan

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 119, Page(s) 155012

Abstract: ... mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound ...

Abstract	Background: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa that is mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound that is widely used to treat respiratory diseases such as AR. However, the underlying mechanism of the effect of XQLT on AR remains unclear. Purpose: To elucidate the effect of XQLT on ovalbumin (OVA)-induced AR and the mechanisms of action. Methods: The therapeutic efficacy of XQLT was evaluated in a well-established OVA-induced AR mouse model. Nasal symptoms were analyzed, type 2 cytokines and OVA-sIgE levels were measured, nasal mucosa tissues were collected for histological analysis, and the changes of Group 2 innate lymphoid cells (ILC2s) and the IL-33/ST2 and JAK/STAT signaling pathways in the nasal mucosa were observed. Results: XQLT significantly alleviated the nasal symptoms and histological damage to the nasal mucosa in AR mice, and reduced the levels of type 2 cytokines and OVA-sIgE. In addition, after XQLT treatment, the numbers of ILC2s in the nasal mucosa of AR mice were reduced, and the mRNA levels of the transcription factors GATA3 and ROR-α were decreased. Moreover, IL-33/ST2 signaling pathway was inhibited. The costimulatory cytokine associated JAK/STAT signaling pathway was also inhibited in ILC2s. Conclusion: Our study demonstrated that XQLT regulated ILC2s through the IL-33/ST2 and JAK/STAT pathways to ameliorate type 2 inflammation in OVA-induced AR. These findings suggest that XQLT might be used to treat AR.
MeSH term(s)	Animals ; Mice ; Ovalbumin ; Immunity, Innate ; Interleukin-1 Receptor-Like 1 Protein/metabolism ; Janus Kinases/metabolism ; Interleukin-33/metabolism ; Lymphocytes ; Signal Transduction ; STAT Transcription Factors/metabolism ; Rhinitis, Allergic/chemically induced ; Rhinitis, Allergic/drug therapy ; Cytokines/metabolism ; Disease Models, Animal ; Mice, Inbred BALB C
Chemical Substances	Ovalbumin (9006-59-1) ; sho-seiryu-to ; Interleukin-1 Receptor-Like 1 Protein ; Janus Kinases (EC 2.7.10.2) ; Interleukin-33 ; STAT Transcription Factors ; Cytokines
Language	English
Publishing date	2023-08-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.155012
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Zs.A 4115: Show issues

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Article ; Online: Xiao Chai Hu Tang alleviates the pancreatic tumorigenesis via improving the mtDNA N6-Methyladenine modification mediated mitochondrial dysfunction in Syrian hamster model.

Cai, Jun / Shen, Wenyuan / Zhang, Guixian / Li, Xia / Shen, Hongsheng / Li, Wenchang / Tan, Cheng / Zhang, Ting / Shi, Mengrou / Yang, Zibo / Li, Yuan / Liu, Hongbin / Zhao, Xiumei

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 116, Page(s) 154840

Abstract: ... Although Xiao Chai Hu Tang (XCHT) has a good therapeutic effect on pancreatic cancer patients with advanced ...

Abstract	Background: Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which is a highly malignant tumor and lack of effective treatment. Although Xiao Chai Hu Tang (XCHT) has a good therapeutic effect on pancreatic cancer patients with advanced stage, the effect and mechanism of XCHT remains unclear in pancreatic tumorigenesis. Purpose: To assess the therapeutic effects of XCHT on the malignant transformation from PanIN to PDAC and to reveal its mechanisms of pancreatic tumorigenesis. Methods: Syrian golden hamster were induced by N-Nitrosobis (2-oxopropyl) amine (BOP) to establish the pancreatic tumorigenesis model. The morphological changes of pancreatic tissue were observed by H&E and Masson staining; the Gene ontology (GO) analysis the transcriptional profiling changes; the mitochondrial ATP generation, mitochondrial redox status, mitochondrial DNA (mtDNA) N6-methyladenine (6mA) level and relative mtDNA genes expressions were examined. In addition, immunofluorescence detect the cell localization of 6mA in human pancreatic cancer PANC1 cell. Using the TCGA database, the prognostic effect of mtDNA 6mA demethylation ALKBH1 expression on pancreatic cancer patients was analyzed. Results: We confirmed the mtDNA 6mA levels were gradually increased with the mitochondrial dysfunction in PanINs progression. XCHT showed the effect to inhibit the occurrence and development of pancreatic cancer in Syrian hamster pancreatic tumorigenesis model. In addition, the lack of ALKBH1 mediated mtDNA 6mA increase, mtDNA coded genes down-expression and abnormal redox status were rescued by XCHT. Conclusions: ALKBH1/mtDNA 6mA mediated mitochondrial dysfunction to induce the occurrence and progression of pancreatic cancer. XCHT can improve ALKBH1 expression and mtDNA 6mA level, regulate the oxidative stress and expression of mtDNA coded genes. This study investigated a new molecular mechanism of pancreatic tumorigenesis, and revealed the therapeutic efficacy of XCHT in pancreatic tumorigenesis for the first time.
MeSH term(s)	Animals ; Cricetinae ; Humans ; DNA, Mitochondrial/genetics ; Mesocricetus ; Bupleurum ; Carcinogenesis ; Cell Transformation, Neoplastic ; Pancreatic Neoplasms/chemically induced ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Mitochondria ; AlkB Homolog 1, Histone H2a Dioxygenase ; Pancreatic Neoplasms
Chemical Substances	DNA, Mitochondrial ; ALKBH1 protein, human (EC 1.14.11.33) ; AlkB Homolog 1, Histone H2a Dioxygenase (EC 1.14.11.33)
Language	English
Publishing date	2023-04-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2023.154840
Database	MEDical Literature Analysis and Retrieval System OnLINE

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