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Article ; Online: Ling-Gui-Zhu-Gan decoction protects against doxorubicin-induced myocardial injury by downregulating ferroptosis.

Yang, Ya-Li / Zhao, Chuan-Zhi / Zhao, Chun-Chun / Wen, Zhong-Yu / Ma, Yao-Yao / Zhao, Xiao-Ni / Wang, Liang / Huang, Jin-Ling / Zhou, Peng

The Journal of pharmacy and pharmacology

2024 Volume 76, Issue 4, Page(s) 405–415

Abstract: Objective: To investigate the mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) protects against ...

Abstract	Objective: To investigate the mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) protects against doxorubicin (DOX)-induced myocardial injury. Methods: In vivo experiment, rats were divided into six groups: normal group, model group (15 mg/kg, DOX), Dex group(150 mg/kg, Dex), LGZGD-L group (2.1 g/kg), LGZGD-M group (4.2 g/kg), and LGZGD-H group (8.4 g/kg). We used HE and Masson staining to observe the histopathological changes, echocardiography to assess the cardiac function, and western blot and RT-qPCR to detect the expressions of Nrf2, GPX4, Fpn1, and Ptgs2. In vitro experiment, we used immunofluorescence to detect ROS production, and RT-qPCR to detect gene expression of GPX4, Fpn1, and Ptgs2. Key findings: In vivo, LGZGD improved cardiac systolic function. LGZGD significantly reduced MDA, LDH, and CK levels, increased SOD activity, enhanced the protein expression of Nrf2, GPX4, and Fpn1, and decreased Ptgs2 levels. In vitro, LGZGD-containing serum significantly reduced ROS, increased the gene expression of GPX4 and Fpn1, and decreased the gene expression of Ptgs2. Furthermore, compared with the LGZGD (si-NC) group, the LGZGD (si-Nrf2) group had decreased gene expression of Nrf2, GPX4, and Fpn1 and increased gene expression of Ptgs2. Conclusions: LGZGD can ameliorate DOX-cardiotoxicity by activating the Nrf2 signaling pathway and inhibiting ferroptosis in cardiomyocytes.
MeSH term(s)	Rats ; Animals ; Ferroptosis ; Cyclooxygenase 2 ; NF-E2-Related Factor 2 ; Reactive Oxygen Species ; Doxorubicin/toxicity ; Plant Extracts
Chemical Substances	ling-gui-zhu-gan decoction ; Cyclooxygenase 2 (EC 1.14.99.1) ; NF-E2-Related Factor 2 ; Reactive Oxygen Species ; Doxorubicin (80168379AG) ; Plant Extracts
Language	English
Publishing date	2024-01-19
Publishing country	England
Document type	Journal Article
ZDB-ID	3107-0
ISSN	2042-7158 ; 0022-3573 ; 0373-1022
ISSN (online)	2042-7158
ISSN	0022-3573 ; 0373-1022
DOI	10.1093/jpp/rgae005
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Article: Exploring the Mechanism of Ling-Gui-Zhu-Gan Decoction in Ventricular Remodeling after Acute Myocardial Infarction Based on UPLC and

Zhou, Peng / Zhang, Meng / Zhao, Xiao-Ni / Tang, Tong-Juan / Wang, Xiang / Huang, Lu-Lu / Kong, Qi / Wang, Liang / Huang, Jin-Ling

Evidence-based complementary and alternative medicine : eCAM

2022 Volume 2022, Page(s) 8593176

Abstract: ... pathophysiological basis for the development of chronic heart failure (CHF). At present, Ling-Gui-Zhu-Gan decoction ...

Abstract	Ventricular remodeling (VR) after acute myocardial infarction (AMI) is an important pathophysiological basis for the development of chronic heart failure (CHF). At present, Ling-Gui-Zhu-Gan decoction (LGZGD) has been widely reported in the clinical treatment and basic research of cardiovascular diseases (CVDs), such as myocardial infarction, heart failure, and angina pectoris. However, the mechanism of LGZGD against VR after AMI remains unclear. Ultra-performance liquid chromatography (UPLC) was applied to investigate the major constituents of LGZGD, and molecular docking was used to predict the targets on the NLRP3/Caspase-1/GSDMD signaling pathway.
Language	English
Publishing date	2022-05-16
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	10.1155/2022/8593176
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Article: Prediction of material foundation of Ling-Gui-Zhu-Gan decoction for chronic heart failure based on molecular docking.

Zhou, Peng / Huang, Jin-Ling

Pakistan journal of pharmaceutical sciences

2021 Volume 33, Issue 4, Page(s) 1459–1464

Abstract: Ling-Gui-Zhu-Gan decoction (LGZGD) is a classic Chinese herbal formula, which has been used ...

Abstract	Ling-Gui-Zhu-Gan decoction (LGZGD) is a classic Chinese herbal formula, which has been used to prevent and treat chronic heart failure (HF). Reliable therapeutics of LGZGD has also been confirmed in clinical practice. In this study, molecular docking has explored the mechanism of LGZGD as an effective treatment for heart failure. Twenty-one known active compounds of LGZGD in serum were screened based on twelve key receptors involved in myocardial damage. There were fourteen active molecules of LGZGD combined strongly with five or more than five protein targets after molecular docking, only seven active molecules of LGZGD combined strongly with ten or more than ten protein targets. The molecular docking provided a forceful tool for searching material foundation and the mechanism of action of TCM formula.
MeSH term(s)	Chronic Disease/drug therapy ; Drugs, Chinese Herbal/pharmacology ; Heart Failure/drug therapy ; Humans ; Molecular Docking Simulation ; Myocardium/pathology ; Plant Extracts/pharmacology
Chemical Substances	Drugs, Chinese Herbal ; Plant Extracts ; ling-gui-zhu-gan decoction
Language	English
Publishing date	2021-02-15
Publishing country	Pakistan
Document type	Journal Article
ZDB-ID	885131-1
ISSN	1011-601X
ISSN	1011-601X
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 6588: Show issues

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Article ; Online: Underlying Mechanism of Traditional Herbal Formula Chuang-Ling-Ye in the Treatment of Diabetic Foot Ulcer through Network Pharmacology and Molecular Docking.

Geng, Jinyuan / Zhou, Guowei / Guo, Song / Ma, Chaoqun / Ma, Jiangfeng

Current pharmaceutical design

2024

Abstract: Background: Chuang-Ling-Ye (CLY) has been clinically proven to be an effective Chinese medicine ...

Abstract	Background: Chuang-Ling-Ye (CLY) has been clinically proven to be an effective Chinese medicine for the treatment of diabetic foot ulcers (DFU). Objectives: This study aimed to investigate the possible mechanism of CLY in relation to DFU using network pharmacology and molecular docking. Materials and methods: Firstly, relevant targets of CLY against DFU were obtained from TCMSP, Swiss Target Prediction database and GEO database. Then, topological analysis was employed by Cytoscape to screen the top 6 core active ingredients and the top 8 hub targets. Furthermore, the OmicShare Tools were applied for gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the results of network pharmacology were verified by molecular docking method. Results: CLY has 61 active compounds and 361 targets after de-duplication, and the top 8 hub targets were EGFR, TP53, CCND1, IL-1B, CREBBP, AR, PTGS2 and PGR. GO enrichment analysis is mainly related to signal transducer activity, receptor activity, and molecular transducer activity. KEGG pathway analysis indicated that these shared targets were primarily focused on AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, and JAK-STAT signaling pathway. Molecular docking results showed that physciondiglucoside, 2-cinnamoyl-glucose and kinobeon A were well bound with EGFR, IL-1B, AR and PTGS2. Conclusion: This study demonstrated that CLY has anti-oxidative stress and anti-inflammatory effects in the treatment of DFU through various constituents, multiple targets, and multiple pathways, which provides a valuable point of reference for future investigations on CLY.
Language	English
Publishing date	2024-02-09
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/0113816128287155240122121553
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Zs.A 4714: Show issues

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Article: LING-GUI-ZHU-GAN DECOCTION ALLEVIATES COGNITIVE DEFICITS IN ALZHEIMER'S DISEASE BY ACTIVATING THE NUCLEAR FACTOR-ERYTHROID FACTOR 2-RELATED FACTOR 2/THE ANTIOXIDANT RESPONSIVE ELEMENT SIGNALING PATHWAY

Zhang, Jingyuan / Yang, Dongqing / Zhao, Juan / Ling, Yun / Zhou, Chunxiang

Current topics in nutraceutical research

2023 Volume 21, Issue 1, Page(s) 1

Language	English
Document type	Article
ZDB-ID	2116319-4
ISSN	1540-7535
Database	Current Contents Nutrition, Environment, Agriculture

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Article ; Online: Methodology improvement for network pharmacology to correct the deviation of deduced medicinal constituents and mechanism: Xian-Ling-Gu-Bao as an example.

Li, Zheng / Qu, Biao / Wu, Xiaowen / Chen, Hongwei / Wang, Jue / Zhou, Lei / Wu, Xiaoyi / Zhang, Wei

Journal of ethnopharmacology

2022 Volume 289, Page(s) 115058

Abstract: ... pharmacology with Xian-Ling-Gu-Bao (XLGB) as a representative, meanwhile, propose the strategies for coping ...

Abstract	Ethnopharmacological relevance: Network pharmacology is extremely adaptive for investigating traditional ethnic drugs, especially the herbal medicines. However, challenges still hang over many related studies due to the limitations in the methodology of conventional network pharmacology. Aim of the study: Our work was aimed to investigate the methodology limitations of conventional network pharmacology with Xian-Ling-Gu-Bao (XLGB) as a representative, meanwhile, propose the strategies for coping with these issues. Materials and methods: Predicted phytochemical constituents formed virtual XLGB. The constituents in realistic XLGB samples was detected by liquid chromatography-mass spectrometry (LC-MS) to correct the constituent deviation resulted from virtual prediction. Multivariate statistical analysis of quantitative target data were used to reveal the relation of target profile between drug and disease. The key constituents and targets were screened and compared between virtual and realistic XLGB through network analysis. After enrichment analysis, reversing network pharmacology was performed to exclude weak targets and re-construct the interaction from key pathways to key targets. Finally, the core constituents and action mechanism of XLGB were deduced. Results: Significant deviation of phytochemical constituents was found between virtual and realistic XLGB. As expected, this deviation led to a cascade of deviation ranging from deduced key constituents to key targets and key pathways. Moreover, many key KEGG pathways were enriched and screened out, however, they were almost irrelevant to the studied disease. These results systemically illustrated the limitations in the methodology of conventional network pharmacology. Importantly, the strategies for coping with these limitations were proposed, such as high-throughput detection of the realistic samples, multivariate analysis of target profile and combined enrichment analysis. Finally, based on the improved network pharmacology, the medicinal constituents and mechanism of XLGB against osteoarthritis were effectively deduced. Conclusions: Our work highlighted the necessity and proposed the strategies for improving the methodology of conventional network pharmacology. The corrected results from improved network pharmacology provided promising directions for future research on XLGB.
MeSH term(s)	Animals ; Chromatography, Liquid ; Drugs, Chinese Herbal/chemistry ; Drugs, Chinese Herbal/pharmacology ; Mass Spectrometry ; Network Pharmacology/methods ; Osteoarthritis/drug therapy ; Rats
Chemical Substances	Drugs, Chinese Herbal ; xian ling gu bao
Language	English
Publishing date	2022-02-01
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.2022.115058
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1494: Show issues

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Article ; Online: Exploring the Mechanism of Ling-Gui-Zhu-Gan Decoction in Ventricular Remodeling after Acute Myocardial Infarction Based on UPLC and In Vivo Experiments

Peng Zhou / Meng Zhang / Xiao-ni Zhao / Tong-juan Tang / Xiang Wang / Lu-lu Huang / Qi Kong / Liang Wang / Jin-ling Huang

Evidence-Based Complementary and Alternative Medicine, Vol

2022 Volume 2022

Abstract: ... pathophysiological basis for the development of chronic heart failure (CHF). At present, Ling-Gui-Zhu-Gan decoction ...

Abstract	Ventricular remodeling (VR) after acute myocardial infarction (AMI) is an important pathophysiological basis for the development of chronic heart failure (CHF). At present, Ling-Gui-Zhu-Gan decoction (LGZGD) has been widely reported in the clinical treatment and basic research of cardiovascular diseases (CVDs), such as myocardial infarction, heart failure, and angina pectoris. However, the mechanism of LGZGD against VR after AMI remains unclear. Ultra-performance liquid chromatography (UPLC) was applied to investigate the major constituents of LGZGD, and molecular docking was used to predict the targets on the NLRP3/Caspase-1/GSDMD signaling pathway. In vivo, histological changes in the myocardium were visualized using HE staining and Masson staining, and cardiomyocyte apoptosis was detected using TUNEL. IL-1β activity in rat serum was determined by ELISA. Finally, NLRP3, Caspase-1, and GSDMD expressions were analyzed through RT-qPCR and Western blotting. The results showed that 8 authentic reference substances have been detected in LGZGD. Molecular docking showed that the major chemical constituents of LGZGD had a good binding activity with NLRP3, Caspase-1, and GSDMD. Our results showed that LGZGD treatment markedly improved cardiac pathology, decreased cardiomyocyte apoptosis, reduced IL-1β activity, and regulated the expression of genes and proteins related to the NLRP3/Caspase-1/GSDMD signal pathway. These results suggest that LGZGD protects against VR after AMI through NLRP3/Caspase-1/GSDMD signal pathway.
Keywords	Other systems of medicine ; RZ201-999
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Ling-Gui-Zhu-Gan Decoction Protects H9c2 Cells against H

Wang, Xiang / Tang, Tongjuan / Zhai, Mengting / Ge, Ruirui / Wang, Liang / Huang, Jinling / Zhou, Peng

Evidence-based complementary and alternative medicine : eCAM

2020 Volume 2020, Page(s) 8860603

Abstract: Objectives: Ling-Gui-Zhu-Gan decoction (LGZGD) is a potentially effective treatment ...

Abstract	Objectives: Ling-Gui-Zhu-Gan decoction (LGZGD) is a potentially effective treatment for heart failure, and it showed significant anti-inflammatory potential in our previous studies. However, its ability to ameliorate heart failure through regulation of oxidative stress response is still unknown. This study was aimed to investigate the protective effect of LGZGD-containing serum on H Methods: Eighteen rats were randomly divided into two groups: the blank control group and LGZGD group. The LGZGD group rats were administrated with 8.4 g/kg/d LGZGD for seven consecutive days through gavage, while the blank control group rats were given an equal volume of saline. The serum was extracted from all the rats. To investigate the efficacy and the underlying mechanism of LGZGD, we categorized the H9c2 cells into groups: the control group, model group, normal serum control (NSC) group, LGZGD group, LGZGD + all-trans-retinoic acid (ATRA) group, and ATRA group. Malonedialdehyde (MDA) and superoxide dismutase (SOD) were used as markers for oxidative stress. Dichlorodihydrofluorescin diacetate (DCFH-DA) staining was used to measure the levels of reactive oxygen species (ROS). The apoptosis rate was detected using flow cytometry. The expression levels of pro-caspase-3, cleaved-caspase-3, Bcl-2, Bax, Keap1, Nrf2, and HO-1 were measured using western blotting. The mRNA levels of Keap1, Nrf2, and HO-1 were measured using RT-qPCR. Results: The LGZGD attenuated injury to H9c2 cells and reduced the apoptosis rate. It was also found to upregulate the SOD activity and suppress the formation of MDA and ROS. The expression levels of pro-caspase-3 and Bcl-2 were significantly increased, while those of cleaved-caspase-3 and Bax were decreased in the LGZGD group compared with the model group. As compared with the model group, the LGZGD group demonstrated decreased Keap1 protein expression and significantly increased Nrf2 nuclear expression and Nrf2-mediated transcriptional activity. ATRA was found to reverse the LGZGD-mediated antioxidative and antiapoptotic effect on injured H9c2 cells induced by H Conclusion: Our results demonstrated that LGZGD attenuated the H
Language	English
Publishing date	2020-11-30
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	10.1155/2020/8860603
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 5995: Show issues

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Article: Shen-Ling-Bai-Zhu-San Enhances the Antipneumonia Effect of Cefixime in Children by Ameliorating Gut Microflora, Inflammation, and Immune Response.

Feng, Jinli / Zhang, Cheng / Chen, Houjun / Chen, Ziliang / Chen, Yongfeng / He, Degen / Pan, Qianyi / Zhou, Yongmao / Chen, Zhaoyang / Zhuang, Xiaozheng

publication RETRACTED

Evidence-based complementary and alternative medicine : eCAM

2022 Volume 2022, Page(s) 7752426

Abstract: Objective: Shen-Ling-Bai-Zhu-San (SLBZS) is used for treating gastrointestinal disorders ...

Abstract	Objective: Shen-Ling-Bai-Zhu-San (SLBZS) is used for treating gastrointestinal disorders. However, the role of SLBZS in treating pneumonia in children is still unclear. Methods: In this study, children (≥2 and <9 years) with pneumonia were treated with 0.1 g cefixime (cefixime group) or 0.1 g cefixime + 9 g SLBZS (SLBZS + cefixime). The drugs were administered twice daily for 10 days. The therapeutic effects of the two groups were compared. The white blood cell (WBC), neutrophil, and lymphocyte counts; neutrophil-lymphocyte ratio (NLR); serum inflammatory factor levels; and gut microflora were assessed. Results: The clinical efficacy of SLBZS + cefixime treatment of pneumonia in children was higher than that of cefixime alone (93.3% Conclusion: SLBZS enhanced the antipneumonia effect of cefixime in children with pneumonia by ameliorating gut microflora, inflammation, and immune response.
Language	English
Publishing date	2022-09-07
Publishing country	United States
Document type	Journal Article ; Retracted Publication
ZDB-ID	2171158-6
ISSN	1741-4288 ; 1741-427X
ISSN (online)	1741-4288
ISSN	1741-427X
DOI	10.1155/2022/7752426
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 5995: Show issues

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Article: Methodology improvement for network pharmacology to correct the deviation of deduced medicinal constituents and mechanism: Xian-Ling-Gu-Bao as an example

Li, Zheng / Qu, Biao / Wu, Xiaowen / Chen, Hongwei / Wang, Jue / Zhou, Lei / Wu, Xiaoyi / Zhang, Wei

Journal of ethnopharmacology. 2022 May 10, v. 289

2022

Abstract: ... limitations of conventional network pharmacology with Xian-Ling-Gu-Bao (XLGB) as a representative, meanwhile ...

Abstract	Network pharmacology is extremely adaptive for investigating traditional ethnic drugs, especially the herbal medicines. However, challenges still hang over many related studies due to the limitations in the methodology of conventional network pharmacology. Our work was aimed to investigate the methodology limitations of conventional network pharmacology with Xian-Ling-Gu-Bao (XLGB) as a representative, meanwhile, propose the strategies for coping with these issues. Predicted phytochemical constituents formed virtual XLGB. The constituents in realistic XLGB samples was detected by liquid chromatography-mass spectrometry (LC-MS) to correct the constituent deviation resulted from virtual prediction. Multivariate statistical analysis of quantitative target data were used to reveal the relation of target profile between drug and disease. The key constituents and targets were screened and compared between virtual and realistic XLGB through network analysis. After enrichment analysis, reversing network pharmacology was performed to exclude weak targets and re-construct the interaction from key pathways to key targets. Finally, the core constituents and action mechanism of XLGB were deduced. Significant deviation of phytochemical constituents was found between virtual and realistic XLGB. As expected, this deviation led to a cascade of deviation ranging from deduced key constituents to key targets and key pathways. Moreover, many key KEGG pathways were enriched and screened out, however, they were almost irrelevant to the studied disease. These results systemically illustrated the limitations in the methodology of conventional network pharmacology. Importantly, the strategies for coping with these limitations were proposed, such as high-throughput detection of the realistic samples, multivariate analysis of target profile and combined enrichment analysis. Finally, based on the improved network pharmacology, the medicinal constituents and mechanism of XLGB against osteoarthritis were effectively deduced. Our work highlighted the necessity and proposed the strategies for improving the methodology of conventional network pharmacology. The corrected results from improved network pharmacology provided promising directions for future research on XLGB.
Keywords	liquid chromatography ; mass spectrometry ; multivariate analysis ; osteoarthritis ; pharmacology ; phytochemicals ; prediction ; traditional medicine
Language	English
Dates of publication	2022-0510
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.2022.115058
Database	NAL-Catalogue (AGRICOLA)

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