Liquiritigenin alleviates doxorubicin-induced chronic heart failure via promoting ARHGAP18 and suppressing RhoA/ROCK1 pathway

Xu, Zhibing; Liu, Chenping; Xu, Hanchen; Zhang, Lifen; Li, Liang; Wang, Yi; Zhu, Yuanqing; Yang, Limeng; Huang, Dan

doi:10.1016/j.yexcr.2022.113008

Cited by 15 publications

(8 citation statements)

References 33 publications

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“…28) The decrease in elevated LDH, CK-MB, and cTnT levels induced by LG in CIA mice confirmed the cardioprotective effect of LG, which has been reported in previous studies. 29) Moreover, our H&E and Masson staining showed that the disorganized myocardial filament arrangement, massive inflammatory infiltration, and extensive fibrous connective tissue formation were relieved by LG, further indicating the presence of cardiac involvement in RA and the protective role of LG on inflammation and fibrosis in the heart. The fibrotic reaction in the heart is a dynamic process in which TGF-β1 is a pivotal fibrogenic cytokine that regulates organ fibrosis and dysfunction.…”

Section: Discussionmentioning

confidence: 72%

Liquiritigenin Attenuated Collagen-Induced Arthritis and Cardiac Complication <i>via</i> Inflammation and Fibrosis Inhibition in Mice

Ning

Cao

et al. 2023

Chem. Pharm. Bull.

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Rheumatoid arthritis (RA) is a common autoimmune disease with increased cardiovascular disease risk. Liquiritigenin (LG) is a triterpene with anti-inflammatory properties. Our study aimed to explore the effect of LG on RA and the cardiac complication. Collagen-induced arthritis (CIA) mice with LG treatment exhibited obvious alleviation in histopathological changes, accompanied by the decreased expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-17A in synovium and serum. LG attenuated cartilage destruction by reducing matrix metalloproteinase (MMP)-3 and MMP-13 expression in the synovium of CIA mice. The echocardiography results proved the alleviation of cardiac dysfunction in CIA mice. The electrocardiogram, biochemical, and histochemical analysis proved the cardioprotection effect of LG against RA. The decreased expression of inflammatory factors (TNF-α, IL-1β, and IL-6) and fibrotic markers (fibronectin, Collagen I, and Collagen III) in cardiac tissues of CIA mice further corroborated the attenuation of myocardial inflammation and fibrosis by LG. Mechanistic studies showed that LG could inhibit transforming growth factor β-1 (TGF-β1) and phos-Smad2/3 expression in cardiac tissues of CIA mice. Our study suggested that LG could relieve RA and its cardiac complication probably by inhibiting the TGF-β1/Smad2/3 pathway. All these suggested that LG might be a potential candidate for RA and its cardiac complication therapy.

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Section: Discussionmentioning

confidence: 72%

Liquiritigenin Attenuated Collagen-Induced Arthritis and Cardiac Complication <i>via</i> Inflammation and Fibrosis Inhibition in Mice

Ning

Cao

et al. 2023

Chem. Pharm. Bull.

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“…Liquiritigenin belongs to the class of favonoids with anti-infammatory, antioxidant, and estrogenic properties. Experiments show that liquiritigenin can reduce ROS generation and lipid accumulation, down-regulate infammatory response, and improve cardiac function [70][71][72]. In addition, liquiritigenin was shown to Evidence-Based Complementary and Alternative Medicine attenuate myocardial fbrosis and inhibit myocardial apoptosis through Akt/ERK signaling pathway [73].…”

Section: Discussionmentioning

confidence: 99%

To Explore the Key Active Compounds and Therapeutic Mechanism of Guizhi Gancao Decoction in Coronary Heart Disease by Network Pharmacology and Molecular Docking

Yuan

Yitao

2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Coronary heart disease (CHD) is the leading cause of death from cardiovascular disease and has become an important public health problem worldwide. Guizhi Gancao Decoction (GGD) has been shown to be used in the treatment of CHD with good efficacy, but its specific therapeutic mechanism and active ingredients have not been fully clarified. This study aims to identify the active compounds and key targets of GGD in the treatment of CHD, explore the therapeutic mechanism of GGD, and provide candidate compounds for anti-CHD drug development. Methods. The main compounds of GGD were determined by UPLC-MS/MS analysis and screened by SwissADME. The corresponding targets of GGD compounds were obtained from SwissTargetPrediction, and the targets of CHD were obtained from the HERB and GeneCards databases. The STRING 11.5 database was used to analyze the PPI (Protein-Protein Interactions) network of potential therapeutic targets of GGD compounds. Cytoscape 3.7.2 was used to construct target-related networks and find core targets. The GEO database was used to validate the differential expression of core targets. The PANTHER Classification System was used to functionally classify potential therapeutic targets for GGD. The GO biological process analysis and KEGG pathway analysis of targets were completed by DAVID 6.8 database. AutoDockTools 1.5.6 and PyMol 2.5.2 were used to perform molecular docking of core targets with the active GGD compounds. Results. 7 active GGD compounds were obtained based on UPLC-MS/MS and pharmacological parameter evaluation, which corresponded to 131 CHD-related targets. Among them, EGFR, MAPK3, RELA, CCND1, ESR1, PTGS2, NR3C1, CYP3A4, MMP9, and PTPN11 were considered core targets. According to the targets related to CHD, glycyrrhetinic acid, liquiritigenin, and schisandrin are considered key active ingredients. GO biological process and KEGG analysis indicated that the potential targets of GGD in the treatment of CHD involve a variety of biological processes and therapeutic mechanisms. Molecular docking results showed that both the core targets and the corresponding compounds had the good binding ability. Conclusions. This study contributes to a more comprehensive understanding of the therapeutic mechanism and active ingredients of GGD for CHD and provides candidate compounds for drug development of CHD.

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“…It is reported that various components in LGZGD have pharmacological activities related to alleviating AMI symptoms. [8][9][10][11][12][23][24][25][26] In Figure 3 and Tables 3, S2 and S3, the highest content in the blood after administration was that of PA, followed by DMA and GHA. After medium-dose administration, AL-I and AL-II were rapidly absorbed, with…”

Section: Pharmacokinetic Studymentioning

confidence: 97%

“…Dehydrotumulosic acid (DTA), atractylodin (AD), liquiritigenin (LG), glycyrrhizic acid (GA) and licochalcone A (LCA-A) are natural components from traditional Chinese medicine (TCM), and they are capable of improving chronic heart failure through multiple pathways both in vivo and in vitro. [8][9][10][11][12] Furthermore, the efficacy of TCM is attributed to its multi-component characteristics.…”

Section: Introductionmentioning

confidence: 99%

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,

Ge,

Wang

et al. 2023

Rapid Comm Mass Spectrometry

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RationaleLing‐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.MethodsA 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.ResultsIt 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).ConclusionsThe 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.

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Liquiritigenin alleviates doxorubicin-induced chronic heart failure via promoting ARHGAP18 and suppressing RhoA/ROCK1 pathway

Cited by 15 publications

References 33 publications

Liquiritigenin Attenuated Collagen-Induced Arthritis and Cardiac Complication <i>via</i> Inflammation and Fibrosis Inhibition in Mice

Liquiritigenin Attenuated Collagen-Induced Arthritis and Cardiac Complication <i>via</i> Inflammation and Fibrosis Inhibition in Mice

To Explore the Key Active Compounds and Therapeutic Mechanism of Guizhi Gancao Decoction in Coronary Heart Disease by Network Pharmacology and Molecular Docking

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

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