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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: Three-dimensional stress rotation and control mechanism of deep tunneling incorporating generalized Zhang–Zhu strength-based forward analysis

Cai, Wuqiang / Zhu, Hehua / Liang, Wenhao

Engineering geology. 2022 Oct., v. 308

2022

Abstract: ... Zhang–Zhu (GZZ) strength criterion are performed to investigate the principal stress rotation behavior ...

Abstract	Deep rock tunneling exhibits a significant three-dimensional (3D) space effect. The complex stress path and extrusion deformation during excavation are the most significant and decisive factors in the stability and construction safety of a deep tunnel. 3D and forward numerical analyses based on generalized Zhang–Zhu (GZZ) strength criterion are performed to investigate the principal stress rotation behavior and active control mechanism during deep tunneling. The surrounding rock element experiences significant stress rotations because of the sharply increased shear stress (τᵣy) near the tunnel face. A dimensionless stress index (τᵣy/I₁) is proposed to quantitatively evaluate the principal stress rotation during excavation. τᵣy/I₁ increases with increasing buried depth, and the deep tunnel presents significant principal stress rotation that reaches a large τᵣy/I₁ value. The mechanical behavior of the advanced core rock is primarily affected by the strengthening parameter, geological strength index (GSI). Strengthening of the core rock can greatly improve the stress conditions and mechanical behavior, increase the strength of the rock mass, and reduce the stress rotation. The pre-extrusion deformation of the core rock and pre-convergence of the surrounding rock are discovered to follow a consistency law, which suggests that the pre-convergence deformation and surrounding rock stability near the tunnel face depend on the extrusion deformation of the tunnel face. The GZZ strength-based 3D forward analysis and stress control method proposed in this study can enhance the design and construction of deep and ultra-deep tunnels by weakening the 3D space effect (e.g., tunnel face extrusion and stress rotation) and exerting the strength potential (self-bearing capacity) of a rock mass.
Keywords	control methods ; deformation ; extrusion ; face ; geology ; mechanical properties ; shear stress
Language	English
Dates of publication	2022-10
Publishing place	Elsevier B.V.
Document type	Article
ISSN	0013-7952
DOI	10.1016/j.enggeo.2022.106806
Database	NAL-Catalogue (AGRICOLA)

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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: 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
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Article ; Online: Pharmacokinetic evaluation of 24 representative components of Ling-Gui-Zhu-Gan decoction in acute myocardial infarction model rats via a validated ultrahigh-performance liquid chromatography-tandem mass spectrometry method.

Li, Jing / Ge, Ruirui / Wang, Feng / Gu, Jinfan / Zuo, Mengyu / Tang, Tongjuan / Ge, Xinru / Niu, Yingchao / Wang, Liang / Huang, Jinling / Chen, Jian

Rapid communications in mass spectrometry : RCM

2023 Volume 37, Issue 19, Page(s) e9620

Abstract: Rationale: Ling-Gui-Zhu-Gan decoction (LGZGD), one of the 100 herbal classic formulas, is ...

Abstract	Rationale: Ling-Gui-Zhu-Gan decoction (LGZGD), one of the 100 herbal classic formulas, is clinically used to treat chronic heart failure with remarkable curative effect. However, LGZGD pharmacokinetic parameters in pathological model rats are poorly understood, in particular for special components. As physicochemical properties are specific to each representative component, no standard sample preparation is available for absolute quantification of representative components of LGZGD in rat plasma. Methods: A specific, sensitive and high-throughput ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) method capturing 24 representative components was developed and applied to evaluate the pharmacokinetic parameters of LGZGD in acute myocardial infarction (AMI) rat plasma after intragastric administration (2.4, 4.8 and 9.6 g/kg). Precipitation and extraction were selected and optimized for plasma preparation, and isopropanol precipitation could offer higher recovery and broader coverage. Results: It was expected that AMI could cause less absorption and slower elimination of most of active components of LGZGD. Most of newly reported special components absorbed quickly and eliminated slowly. The average elimination half-life of the 24 representative components was 10.09 h, which is consistent with the dosage of LGZGD (twice daily). Conclusions: The specificity, linearity, precision and accuracy, recovery, matrix effect and stability were validated according to Food and Drug Administration guidance. The validation results demonstrated that the method could be applied to evaluate the pharmacokinetic parameters of LGZGD in AMI rats. The pharmacokinetic parameters showed substantial improvement in quality research of LGZGD, thereby laying the groundwork for preclinical and clinical trials in chronic heart failure clinical efficacy.
MeSH term(s)	United States ; Animals ; Rats ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Heart Failure ; Myocardial Infarction/drug therapy
Chemical Substances	ling-gui-zhu-gan decoction
Language	English
Publishing date	2023-09-12
Publishing country	England
Document type	Journal Article
ZDB-ID	58731-x
ISSN	1097-0231 ; 0951-4198
ISSN (online)	1097-0231
ISSN	0951-4198
DOI	10.1002/rcm.9620
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Zs.A 3461: Show issues

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Article ; Online: Transcriptome profiling Revealed the potential mechanisms of Shen Lin Bai Zhu San n-butanol extract on DSS induced Colitis in Mice and LC-MS analysis.

Qu, Qian / Li, Shu-Peng / Dong, Qi / Du, Hong-Liang / Wang, Zhi-Hua / Ma, Yi-Mu / Gong, Xiao-Pei / Ding, Yi-Qing / Zhou, Jing / Chen, Jia-Yan / Liu, Meng-Jie / Lv, Wei-Jie / Guo, Shi-Ning

Phytomedicine : international journal of phytotherapy and phytopharmacology

2023 Volume 110, Page(s) 154645

Abstract: ... in gastrointestinal tract. Shen Ling Bai Zhu San (SLBZS), which has a long history of use in Traditional Chinese Medicine ...

Abstract	Background: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder in gastrointestinal tract. Shen Ling Bai Zhu San (SLBZS), which has a long history of use in Traditional Chinese Medicine (TCM), has been widely used to treat gastrointestinal diseases. The isolated fractions of TCM have also been proved to possess an important potential for treating diseases, which are due to their effective components. Purpose: In this study, we examined the possibility that SLBZS and its isolated active fractions may prevent DSS-induced colitis, and investigated the potential mechanisms by regulating genetic profile of colon. Methods: Colitis mice were induced by 2.5% DSS for 7 days, and then SLBZS and different SLBZS extracts were administrated to protect the mice for 7 days. Body weight, diarrhea, bleeding in stool, colon length, spleen weight, cytokines of serum and colon and pathology of colon were assessed. The level of Ginsenoside Rg1, Re and Rb1 in different SLBZS extracts and qualitative analysis of n-butanol extract of SLBZS (S-Nb) was performed by HPLC and LC-MS, respectively. And the effects of S-Nb on the transcriptome in colitis were investigated. Results: Our results showed that SLBZS and S-Nb significantly regained body weight, reduced DAI, splenomegaly and the length of colon and attenuated histological damage of the colon. Meanwhile, SLBZS and S-Nb markedly reduced the levels of TNF-α, IL-1β and IL-6 and increased the level of IL-10 in serum and colon. These effects may be associated with the high levels of Ginsenoside Rg1, Re and Rb1 and rich variety of compounds in S-Nb including 6 ginsenosides, glycyrrhizin, L-tryptophan, and so on. Transcriptome analysis revealed that S-Nb selectively regulated 103 differentially expressed genes (DEGs), 36 of which were changed in DSS-induced mice. And the genes of Per2, Per3, Npy and Serpina3m were closely related to colitis and also restored by S-Nb with different extent. Remarkably, these DEGs modulated the biological functions of colitis mice, including extracellular region, response to external stimulus, MAPK signaling pathway and arginine and proline metabolism. Conclusions: These data indicated that SLBZS and S-Nb blunted DSS-induced colitis by modulating differentially expression gene profile and biological functions based on their ginsenosides and rich compounds.
MeSH term(s)	Mice ; Animals ; Ginsenosides/pharmacology ; 1-Butanol/pharmacology ; Butanols/pharmacology ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Colitis/chemically induced ; Colitis/drug therapy ; Colitis/pathology ; Colon/pathology ; Chronic Disease ; Gene Expression Profiling ; Body Weight ; Dextran Sulfate ; Disease Models, Animal ; Mice, Inbred C57BL ; Cytokines
Chemical Substances	ginsenoside Rg1 (PJ788634QY) ; Ginsenosides ; 1-Butanol (8PJ61P6TS3) ; Butanols ; Dextran Sulfate (9042-14-2) ; Cytokines
Language	English
Publishing date	2023-01-03
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.2023.154645
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Zs.A 4115: 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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Book: Guan zi jiao zhu

Li, Xiangfeng / Guan, Zhong / Liang, Yunhua

(Xin bian zhu zi ji cheng)

2012

Author's details	Li xiang feng zhuan; liang yun hua zheng li
Series title	Xin bian zhu zi ji cheng
Language	Chinese
Size	21 cm
Edition	Di 1 ban
Publisher	Zhong hua shu ju
Publishing place	Bei jing
Document type	Book
Database	Former special subject collection: coastal and deep sea fishing

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Book: Guan zi jiao zhu

Li, Xiangfeng / Guan, Zhong / Liang, Yunhua

(Xin bian zhu zi ji cheng)

2012

Author's details	Li xiang feng zhuan; liang yun hua zheng li
Series title	Xin bian zhu zi ji cheng
Language	Chinese
Size	21 cm
Edition	Di 1 ban
Publisher	Zhong hua shu ju
Publishing place	Bei jing
Document type	Book
Database	Former special subject collection: coastal and deep sea fishing

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Book: Guan zi jiao zhu

Li, Xiangfeng / Guan, Zhong / Liang, Yunhua

(Xin bian zhu zi ji cheng)

2012

Author's details	Li xiang feng zhuan; liang yun hua zheng li
Series title	Xin bian zhu zi ji cheng
Language	Chinese
Size	21 cm
Edition	Di 1 ban
Publisher	Zhong hua shu ju
Publishing place	Bei jing
Document type	Book
Database	Former special subject collection: coastal and deep sea fishing

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