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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
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Zs.A 6588: Show issues

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Article ; Online: Successful treatment of immune-related cystitis by Chai-Ling-Tang (Sairei-To) in a gastric carcinoma patient: Case report and literature review.

Wang, Zhiqiang / Zhu, Liping / Huang, Yong / Peng, Ling

Explore (New York, N.Y.)

2022 Volume 19, Issue 3, Page(s) 458–462

Abstract: ... Oral administration of Chai-Ling-Tang (Sairei-To) alleviated lower urinary tract symptoms (LUTS). Histological ... The dose of Chai-Ling-Tang was maintained and stopped 2 months later without recurrence of LUTS ... shows that Chai-Ling-Tang is safe and effective for treating immune-related cystitis. The detailed ...

Abstract	Background: Immune checkpoint inhibitors (ICIs) have changed the landscape of advanced cancer treatment. However, immune checkpoint inhibitors can trigger effector T cells against self-antigens as well as tumor antigens, resulting in immune-related toxicities in normal organs, referred to as immune-related adverse events (irAEs). Case summary: A 56-year-old man with undifferentiated gastric carcinoma received sintilimab plus paclitaxel and tegafur therapy. After five cycles of treatment, the patient was referred to the hospital for sudden onset urinary frequency, micturition pain, and urinary incontinence. Cystoscopy revealed the entire bladder mucosa was red and edematous but there was no evidence of tumor. Oral administration of Chai-Ling-Tang (Sairei-To) alleviated lower urinary tract symptoms (LUTS). Histological analysis revealed numerous infiltrates of CD3-positive and CD8-positive cells into the urothelium but no atypia, indicating a diagnosis of immune-related cystitis. Interestingly, the urothelial epithelium infiltrated by lymphocytes and subepithelial inflammatory cells strongly expressed cell boundary PD-L1. The dose of Chai-Ling-Tang was maintained and stopped 2 months later without recurrence of LUTS. Since recovering from cystitis, the patient remains alive with no disease progression. Conclusion: This report shows that Chai-Ling-Tang is safe and effective for treating immune-related cystitis. The detailed mechanism of action requires further investigation.
MeSH term(s)	Male ; Humans ; Middle Aged ; Immune Checkpoint Inhibitors ; Drugs, Chinese Herbal/therapeutic use ; Autoimmune Diseases ; Cystitis/drug therapy ; Carcinoma/drug therapy
Chemical Substances	sairei-to ; Immune Checkpoint Inhibitors ; Drugs, Chinese Herbal
Language	English
Publishing date	2022-04-04
Publishing country	United States
Document type	Review ; Case Reports ; Journal Article
ZDB-ID	2183945-1
ISSN	1878-7541 ; 1550-8307
ISSN (online)	1878-7541
ISSN	1550-8307
DOI	10.1016/j.explore.2022.04.002
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Article: Zhoushi Qi Ling decoction inhibits the progression of castration-resistant prostate cancer in vivo by regulating macrophage infiltration via IL6-STAT3 signaling.

Cao, Hongwen / Wang, Dan / Gao, Renjie / Chen, Lei / Feng, Yigeng / Sun, Peng

Journal of traditional and complementary medicine

2023 Volume 14, Issue 1, Page(s) 19–25

Abstract: ... Western blot.: Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 ...

Abstract	Background and aim: Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits. Experimental procedure: CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot. Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.
Language	English
Publishing date	2023-06-07
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2709698-1
ISSN	2225-4110
ISSN	2225-4110
DOI	10.1016/j.jtcme.2023.05.005
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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
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Article: Qi Ling decoction reduces gastric cancer cell metastasis by inhibiting MMP-9 through the PI3K/Akt signaling pathway.

Chen, Wen / Zhang, Yuheng / Gu, Xiaoqun / Qian, Peiyao / Liu, Wanli / Shu, Peng

American journal of translational research

2021 Volume 13, Issue 5, Page(s) 4591–4602

Abstract: ... the effect of Qi Ling decoction (QLD) on the invasion and metastasis of gastric cancer and its related ...

Abstract	Objective: Traditional Chinese medicine has been increasingly used in the prevention and treatment of gastric cancer, especially in application of compound Chinese medicine. The aim of this study was to investigate the effect of Qi Ling decoction (QLD) on the invasion and metastasis of gastric cancer and its related signaling pathways at the cellular and molecular level in vitro, and explore the mechanism of QLD. Methods: Scratch assay, transwell assay, and adhesion experiments were used to study the effects of QLD and its compounds on gastric cancer. Western blot was employed to detect expression of the PI3K/Akt pathway after administration of QLD. Results: QLD can significantly inhibit the invasion, migration, and adhesion of gastric cancer cells in vitro. The main chemical components of QLD (diosgenin, catechins, and calycosin) can also inhibit the invasion, migration and adhesion of gastric cancer cells. Furthermore, QLD inhibits MMP-9 and affects gastric cancer cell metastasis through the PI3K/Akt pathway. Conclusion: QLD and its three main chemical components can inhibit the invasion, migration, and adhesion of gastric cancer cells, and the mechanism may be related to the PI3K/Akt pathway.
Language	English
Publishing date	2021-05-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2471058-1
ISSN	1943-8141
ISSN	1943-8141
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Article ; Online: Network Pharmacology-Based Strategy Combined with Molecular Docking and in vitro Validation Study to Explore the Underlying Mechanism of Huo Luo Xiao Ling Dan in Treating Atherosclerosis.

Sun, Taoli / Quan, Wenjuan / Peng, Sha / Yang, Dongmei / Liu, Jiaqin / He, Chaoping / Chen, Yu / Hu, Bo / Tuo, Qinhui

Drug design, development and therapy

2022 Volume 16, Page(s) 1621–1645

Abstract: Background: Huo Luo Xiao Ling Dan (HLXLD), a famous Traditional Chinese Medicine (TCM) classical ...

Abstract	Background: Huo Luo Xiao Ling Dan (HLXLD), a famous Traditional Chinese Medicine (TCM) classical formula, possesses anti-atherosclerosis (AS) activity. However, the underlying molecular mechanisms remain obscure. Aim: The network pharmacology approach, molecular docking strategy, and in vitro validation experiment were performed to explore the potential active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. Methods: Several public databases were used to search for active components and targets of HLXLD, as well as AS-related targets. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis. Subsequently, the molecular docking strategy and molecular dynamics simulation were carried out to predict the affinity and stability of active compounds and key targets. In vitro cell experiment was performed to verify the findings from bioinformatics analysis. Results: A total of 108 candidate compounds and 321 predicted target genes were screened. Bioinformatics analysis suggested that quercetin, dihydrotanshinone I, pelargonidin, luteolin, guggulsterone, and β-sitosterol may be the main ingredients. STAT3, HSP90AA1, TP53, and AKT1 could be the key targets. MAPK signaling pathway might play an important role in HLXLD against AS. Molecular docking and molecular dynamics simulation results suggested that the active compounds bound well and stably to their targets. Cell experiments showed that the intracellular accumulation of lipid and increased secretory of TNF-α, IL-1β, and MCP-1 in ox-LDL treated RAW264.7 cells, which can be significantly suppressed by pretreating with dihydrotanshinone I. The up-regulation of STAT3, ERK, JNK, and p38 phosphorylation induced by ox-LDL can be inhibited by pretreating with dihydrotanshinone I. Conclusion: Our findings comprehensively demonstrated the active compounds, key targets, main signaling pathways, and underlying molecular mechanisms of HLXLD in treating AS. These findings would provide a scientific basis for the study of the complex mechanisms underlying disease and drug action.
MeSH term(s)	Atherosclerosis/drug therapy ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Furans ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Phenanthrenes ; Quinones
Chemical Substances	Drugs, Chinese Herbal ; Furans ; Phenanthrenes ; Quinones ; huo luo xiao ling dan ; dihydrotanshinone I (562G9360V6)
Language	English
Publishing date	2022-05-30
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2451346-5
ISSN	1177-8881 ; 1177-8881
ISSN (online)	1177-8881
ISSN	1177-8881
DOI	10.2147/DDDT.S357483
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Article ; Online: Zhoushi Qi Ling decoction represses docetaxel resistance and glycolysis of castration-resistant prostate cancer via regulation of SNHG10/miR-1271-5p/TRIM66 axis.

Cao, Hongwen / Wang, Dan / Sun, Peng / Chen, Lei / Feng, Yigeng / Gao, Renjie

Aging

2021 Volume 13, Issue 19, Page(s) 23096–23107

Abstract: ... of Chinese medicine Zhoushi Qi Ling decoction on the docetaxel resistance of prostate cancer as well ... as elucidate the underlying molecular mechanism. In our study, Qi Ling significantly decreased viability and ... colony formation as well as increased apoptosis of docetaxel-resistant (DR) CRPC cells. Qi Ling-treated ...

Abstract	Docetaxel resistance developed in half of castration-resistant prostate cancer (CRPC) patients hinders its long-term clinical application. The current study was designed to investigate the effects of Chinese medicine Zhoushi Qi Ling decoction on the docetaxel resistance of prostate cancer as well as elucidate the underlying molecular mechanism. In our study, Qi Ling significantly decreased viability and colony formation as well as increased apoptosis of docetaxel-resistant (DR) CRPC cells. Qi Ling-treated DR cells exhibited decreased glucose consumption, lactate release and pyruvate production. Moreover, lncRNA SNHG10 was upregulated in DR tissues of CRPC patients and was negatively correlated with the progression-free survival. Bioinformatics analysis indicated miR-1271-5p as the associated miRNA possibly binding with SNHG10. miR-1271-5p up-regulation dramatically decreased the luciferase activity of SNHG10 in DR cells. SNHG10 knockdown sharply increased the expression of miR1271-5p in DR cells. Targetscan predicted TRIM66 as one of the downstream targets of miR-1271-5p. miR-1271-5p up-regulation drastically reduced luciferase activity as well as TRIM66 expression in DR cells. Also, the knockdown of SNHG10 remarkably suppressed the expression of TRIM66 in DR cells. Additionally, Qi Ling treatment reduced SNHG10 and TRIM66, while increased miR1271-5p, in DR cells. In summary, Qi Ling inhibited docetaxel resistance and glycolysis of CRPC possibly via SNHG10/miR-1271-5p/TRIM66 pathway.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Docetaxel/pharmacology ; Drug Resistance, Neoplasm/drug effects ; Drugs, Chinese Herbal/pharmacology ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Male ; MicroRNAs/genetics ; Prostatic Neoplasms, Castration-Resistant/metabolism ; RNA, Long Noncoding/genetics ; Warburg Effect, Oncologic/drug effects
Chemical Substances	Antineoplastic Agents ; Drugs, Chinese Herbal ; Intracellular Signaling Peptides and Proteins ; MIRN1271 microRNA, human ; MicroRNAs ; RNA, Long Noncoding ; TRIM66 protein, human ; Docetaxel (15H5577CQD)
Language	English
Publishing date	2021-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.203602
Database	MEDical Literature Analysis and Retrieval System OnLINE

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