Frontiers in Pharmacology
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2025
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IF 4.8
Jue Bai,Si-Yuan Yang,Shao-Mei Yu,Ying Cao,Chang-Han Ma,Xuan-Yi Hu,Xiong Chen,Ying-Nan Song,Hong-Jin Chen
Background: Myocardial ischemia/reperfusion injury (MIRI) is a critical problem in cardiovascular medicine, often occurring after coronary revascularization procedures or cardiopulmonary bypass. The characters of MIRI are both energy metabolism disturbances and severe myocardium insulin resistance (IR), which exacerbated myocardial damage and cell death. Isoliquiritigenin (ISL), a flavonoid derived from licorice roots (Glycyrrhiza spp.), has demonstrated protective effects on MIRI. However, the potential cardio-protective effects and mechanism of ISL in MIRI remain unclear.Propose: In this study, we aimed to investigate ISL’s therapeutic effects on MIRI. Moreover, we elucidate the underlying mechanisms of ISL regulated myocardium insulin resistance in vivo and in vitro.Methods: In vivo, SD rats underwent left anterior descending coronary artery ligation/reperfusion to induce MIRI. Chest echocardiography was performed to monitor cardiac function post-reperfusion, followed by measurement of myocardial injury and IR markers. In vitro, H9C2 cardiomyocytes subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Markers associated with myocardial injury and IR were assessed. Then, we identified potential therapeutic targets IGFBP5 for MIRI by network pharmacology and molecular docking analysis. Finally, lentivirus were used to silence or over-express IGFBP5 to elucidate the role of IGFBP5 in regulating the therapeutic effects of ISL on IR in MIRI.Results: In the present study, In vivo experiments demonstrated that ISL attenuated myocardial infarct size, decreased serum markers of myocardial injury, improved left ventricular systolic function, and enhanced insulin sensitivity. In vitro data revealed that ISL ameliorated glucose uptake and cell survival rate. Furthermore, ISL increased AKT phosphorylation and upregulated membrane-bound GLUT4 (M-GLUT4) protein expression levels. These effects of ISL are mediated by the induction of IGFBP5, as demonstrated using gene-specific shRNA or overexpression for IGFBP5.Conclusion: Our results reveal that ISL protects against myocardial damage caused by MIRI through the regulation of IR via the IGFBP5/AKT/GLUT4 pathway.
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Oxidative Medicine and Cellular Longevity
·
2018
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IF 4.936
Xinnong Liu,Qingtian Zhu,Min Zhang,Tao Yin,Rong Xu,Weiming Xiao,Jian Wu,Bin Deng,Xuefeng Gao,Weijuan Gong,Guotao Lu,Yanbing Ding
Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.
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International Journal of Nanomedicine
·
2017
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IF 4.3
Fei Gao,Jinming Zhang,Chaomei Fu,Xiaoming Xie,Fu Peng,Jieshu You,Hailin Tang,Zhiyu Wang,Peng Li,Jianping Chen
Isoliquiritigenin (ISL), a natural anti-breast cancer dietary compound, has poor delivery characteristics and low bioavailability. In order to promote the therapeutic outcome of ISL, a tumor-targeting lipid–polymer hybrid nanoparticle (NP) system modified by tumor-homing iRGD peptides has been developed. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. iRGD peptides were anchored on the surface by a postinsertion method (ISL-iRGD NPs). The stable lipid–polymer structure of ISL-iRGD NPs, with high encapsulation and loading efficiency, was confirmed. Compared to free ISL and non-iRGD-modified counterparts, ISL-iRGD NPs showed higher cytotoxicity and cell apoptosis against the different type of breast cancer cells. This was attributable to higher cellular accumulation mediated by the iRGD-integrin recognition and the nanoscale effect. More importantly, based on the active tumor-tissue accumulation by iRGD peptides and the prolonged in vivo circulation by the stealth nanostructure, ISL-iRGD NPs displayed higher tumor-growth inhibition efficiency in 4T1-bearing breast-tumor mouse models. Therefore, the constructed iRGD modified lipid–polymer hybrid NPs would provide a promising drug-delivery strategy to improve ISL in anti-breast cancer efficacy.
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Food Bioscience
·
2024
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IF 4.8
Yushi Wei,Le Deng,Shuling Chen,Xing Hu,Guowen Zhang
The inhibition mechanism of starch digestion by a natural plant active ingredient isoliquiritigenin was studied. The results indicated that isoliquiritigenin effectively decreased the starch hydrolysis through increasing the content of resistant starch, and inhibiting the activities of α-amylase and α-glucosidase. The content of resistant starch increased by 18.85% with the addition of isoliquiritigenin at 8% content. Multispectral analyses showed isoliquiritigenin combined with α-amylase or α-glucosidase to form stable complexes by non-covalent bonds, leading to the enzyme's structure to be loose, which was supported by the results of unstable conformations and an increase in the freedom of amino acid residues of the enzymes in molecular dynamics simulation. Molecular docking demonstrated that isoliquiritigenin bound to the amino acid residues 304–310 nearby the active pocket of α-amylase, and inserted the active site of α-glucosidase competing with the substrate to bind the crucial amino acid residues (Asp215, Asp352 and Glu411), thereby inhibiting α-amylase and α-glucosidase activity. These findings highlight the development potential of isoliquiritigenin as a hypoglycaemic dietary supplement.
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PHYTOTHERAPY RESEARCH
·
2024
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IF 6.1
Liu Yang,Haoran Nie,Yan Du,Xuyang Liu,Bangrong Cai,Jiansheng Li
Acute lung injury (ALI), a systemic inflammatory response with high morbidity, lacks effective pharmacological therapies. Myeloid differentiation protein-2 (MD2) has emerged as a promising therapeutic target for ALI. Herein, we aimed to evaluate the ability of isoliquiritigenin (ISL), a natural flavonoid found in licorice as a novel MD2 inhibitor, to inhibit lipopolysaccharide (LPS)-induced ALI. We established a mouse ALI model and a RAW 264.7 cell injury model through LPS administration. Then, lung injury was assessed through histopathological examination, and the effects of ISL were evaluated using immunofluorescence, western blotting, reverse transcription–quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assays. In addition, the interaction between ISL and MD2 was investigated through co-immunoprecipitation and LPS displacement assays. Molecular docking and liquid chromatography/mass spectrometry analyses were employed to predict the ISL-binding domain of MD2. We found that ISL covalently bound to the Cysteine 133 residue of MD2, disrupting the formation of the LPS/MD2/toll-like receptor 4 complex, and ISL significantly suppressed proinflammatory cytokine production and reactive oxygen species generation in LPS-induced RAW264.7 cells. Moreover, ISL significantly alleviated lung injury in LPS-induced mice, reducing pulmonary microvascular permeability, inflammatory cell infiltration, and inflammatory cytokine expression. The underlying mechanism of ISL involved the inhibition of nuclear factor kappa B and the p38 mitogen-activated protein kinase pathway. Our findings supported that MD2 is the direct target of ISL in mediating its anti-inflammatory response in vivo and in vitro, and it holds potential as a therapeutic candidate for treating ALI and other inflammatory diseases.
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NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 12
·2435-2445
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IF 2.772
Zhang Man,Huang Li-Li,Teng Chen-Huai,Wu Fang-Fang,Ge Li-yun,Shi Yu-Juan,He Zheng-Le,Liu Lei,Jiang Cheng-Jie,Hou Ruo-Nan,Xiao Jian,Zhang Hong-Yu,Chen Da-Qing
Traumatic brain injury (TBI) is a serious public health and medical problem worldwide. Oxidative stress plays a vital role in the pathogenesis of TBI. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important factor in the cellular defense against oxidative stress, is activated following TBI. In this study, the protective effects of Isoliquiritigenin (ILG), a promising antioxidant stress drug, was evaluated as a protective agent against TBI. In a mouse model of controlled cortical impact Injury, we found that the ILG administration reduced the Garcia neuroscore, injury histopathology, brain water content, cerebral vascular permeability, the expression of cleaved caspase3, aquaporin-4, glial fibrillary acidic protein and the increased the expression of neurofilament light chain protein, indicating the protective effects against TBI in vivo. ILG treatment after TBI also restored the oxidative stress and promoted the Nrf2 protein transfer from the cytoplasm to the nucleus. We then used Nrf2−/− mice to test the protective effect of Nrf2 during ILG treatment of TBI. Our findings indicated that Nrf2−/− mice had greater brain injury and oxidative stress than wild-type (WT) mice and ILG was less effective at inhibiting oxidative stress and repairing the brain injury than in the WT mice. In vitro studies in SY5Y cells under oxygen glucose deprivation/re-oxygenation stimulation yielded results that were consistent with those obtained in vivo showing that ILG promotes Nrf2 protein transfer from the cytoplasm to the nucleus. Taken together, our findings demonstrate that Nrf2 is an important protective factor against TBI-induced injuries, which indicates that the protective effects of ILG are mediated by inhibiting oxidative stress after TBI via a mechanism that involves the promotion of Nrf2 protein transfer from the cytoplasm to the nucleus.
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ULTRASONICS SONOCHEMISTRY
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2022
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IF 9.336
Chen Xing,Wen-Qiang Cui,Yue Zhang,Xin-Shu Zou,Jing-You Hao,Si-Di Zheng,Ting-Ting Wang,Xiao-Zhen Wang,Tong Wu,Yan-Yan Liu,Xue-Ying Chen,Shu-Guang Yuan,Zhi-Yun Zhang,Yan-Hua Li
Licorice ( Glycyrrhiza glabra ) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2015
·Vol. 16
·期 8
·17999-18017
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IF 2.862
Bin Li,Benguo Liu,Jiaqi Li,Huizhi Xiao,Junyi Wang,Guizhao Liang
Isoliquiritigenin (ILTG) possesses many pharmacological properties. However, its poor solubility and stability in water hinders its wide applications. The solubility of bioactive compounds can often be enhanced through preparation and delivery of various cyclodextrin (CD) inclusion complexes. The 6-O-α-d-maltosyl-β-CD (G2-β-CD), as one of the newest developments of CDs, has high aqueous solubility and low toxicity, especially stable inclusion characteristics with bioactive compounds. In this work, we for the first time construct and characterize the supermolecular structure of ILTG/G2-β-CD by scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffractometry (XRD). The solubility of ILTG in water at 25 °C rises from 0.003 to 0.717 mg/mL by the encapsulation with G2-β-CD. Our experimental observations on the presence of the ILTG/G2-β-CD inclusion complex are further supported by the ONIOM(our Own N-layer Integrated Orbital molecular Mechanics)-based QM/MM (Quantum Mechanics/Molecular Mechanics) calculations, typically substantiating these supermolecular characteristics, such as detailed structural assignments, preferred binding orientations, selectivity, solvent effects, interaction energies and forces of the ILTG/G2-β-CD inclusion complex. Our results have elucidated how ILTG interacts with G2-β-CD, demonstrating the primary host-guest interactions between ILTG and G2-β-CD, characterized by hydrogen bonds, hydrophobic interactions, electrostatic forces, and conformational effects, are favored for the formation of the ILTG/G2-β-CD inclusion.Keywords:isoliquiritigenin;6-O-α-d-Maltosyl-β-CD;inclusion complex;ONIOM calculation
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ANALYTICAL LETTERS
·
2024
·
IF 1.6
Weijia Tang,Linna Zhu,Ran Li,Michael Adu-Frimpong,Xin Shen,Xiaoxiao Li,Ximing Xu,Shanshan Tong
Herein, a high-sensitive electrochemical sensor based upon a multi-walled carbon nanotubes modified screen-printed carbon electrode (MWCNTs-SPCE) was constructed for the determination of isoliquiritigenin (ISL). The electrochemical properties of ISL on the MWCNTs-SPCE were investigated systematically and a fast and cost-effective method for the determination of ISL was successfully established. A clear irreversible oxidation peak of the ISL was observed at 0.3 V (versus Ag/AgCl) on the MWCNTs-SPCE. The oxidation of ISL on MWCNTs-SPCE was an adsorption reaction accompanied by diffusion. Using differential pulse voltammetry (DPV), we observed that the oxidation peak current of the ISL in phosphate buffer (pH 7) showed a linear relationship from 0.50 to 100 µg/mL and a detection limit of 0.10 µg/mL. This method displayed good repeatability and stability, as well as exhibited excellent selectivity for ISL. Also, we successfully applied the method to determine ISL in Chinese herbal medicine licorice. Validation of the analyses via spike assays showed a recovery rate ranging from 95.39 to 101.00%, which was consistent with high performance liquid chromatography (HPLC).
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Materials Today Communications
·
2025
·
IF 4.5
Rui Yang,Kan Zhang
Epoxy resins are widely utilized in industrial applications owing to their outstanding thermal mechanical performance and chemical resistance. Nevertheless, conventional epoxy resins often suffer from poor storage stability once blended with curing agents, which limits their broader application. To address this limitation, a novel bio-based benzoxazine monomer ( ISO-fa ) was strategically synthesized through molecular design employing isoliquiritigenin, furfurylamine, and paraformaldehyde as raw materials. The incorporation of intramolecular hydrogen bonding imparts latent curing characteristic to this monomer, enabling precise control over the curing process. Besides, the resulting polybenzoxazine ( poly(ISO-fa) ) demonstrated an exceptional integration of thermal properties. When employed to apply as latent curing agent for the epoxy resin (DGEBA), ISO-fa facilitated the development of an intelligent system that combined latent curing behavior with enhanced material performance. Specifically, DGEBA/ISO-fa exhibited significantly improved storage stability and its resulting poly(DGEBA/ISO-fa) showed exceptional performance with a glass transition temperature ( T g ) of 210 °C, a residual char yield of 39.9 % at 800 °C, and a remarkably low heat release capacity (HRC) of 94.53 J·g⁻¹ ·K⁻¹ . This study addresses the limitations of conventional epoxy resins and provides an innovative strategy for developing high-performance single-component epoxy thermosetting systems. Moreover, the newly obtained ISO-fa also represents a practical example of how molecular design can be leveraged to achieve both processability and performance enhancements in advanced materials.
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Scientific Reports
·
2026
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IF 4.9
Li Ruifang,Sun Yan,Feng Mingzhi,Kelsang Drolma,Cai Hanhui,Zhang Jun
Ulcerative colitis (UC) is a chronic disease characterized by intestinal inflammation, mucosal damage, and immune dysregulation. Current treatments are often inadequate, driving the search for alternatives with fewer side effects. Isoliquiritigenin (ISL), a flavonoid from licorice, has demonstrated anti-inflammatory effects, but its efficacy in UC remains uncertain. Male C57BL/6 mice were divided into six groups: Control, DSS model, low-, medium-, and high-dose ISL (25, 50, 100 mg/kg), and 5-aminosalicylic acid (5-ASA, 100 mg/kg). UC was induced by administering 3% DSS, followed by ISL or 5-ASA treatment. Disease activity index (DAI), histopathology, real-time PCR, Western blotting, immunohistochemistry, and 16 S rRNA sequencing were used to assess inflammation, intestinal barrier integrity, and gut microbiota (GM) composition. a Caco-2 cell-based model of UC was developed. After transfection to induce the overexpression of TLR4 and its adaptor protein MyD88, the cells were incubated with ISL. The effects of this intervention were evaluated by measuring the expression of inflammatory cytokines, tight junction-associated proteins, and components of the TLR4/MyD88 signaling pathway. ISL significantly alleviated DSS-induced UC symptoms, such as weight loss and colonic shortening. ISL reduced colonic mucosal damage and inflammatory cell infiltration, downregulated TLR4, MyD88, and phosphorylated NF-κB expression, and lowered TNF-α, IL-1β, and IL-6 levels. It also improved intestinal barrier function by upregulating ZO-1, Claudin-1, and Occludin expression. ISL modulated GM by increasing beneficial bacteria (Muribaculaceae) and reducing pathogenic bacteria (Escherichia-Shigella). Overexpression of TLR4 and MyD88 in the Caco-2 cell line abrogated the protective effects of ISL, as evidenced by increased expression of inflammatory cytokines and downregulated expression of tight junction proteins. Overall, these findings suggest ISL may protects against DSS-induced UC by suppressing the TLR4/MyD88/NF-κB pathway, enhancing intestinal barrier function, and modulating GM, supporting its potential as a therapeutic supplement for UC.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Kunshan Wang,Yingao Zhai,Zenghui Yu,Xuan Zhang,Suzhen Zhou,Jinbo Fan
To mitigate postprandial hyperglycemia, acarbose's excessive α-amylase (AMY) inhibition causes gastrointestinal side effects. Baicalein (Bai), genistein (Gen), and isoliquiritigenin (Isl), featuring 5,6-dihydroxyflavone structures, mildly inhibit AMY. In this study, the inhibitory mechanism of Bai, Gen, and Isl on AMY was determined by integrating multiple analytical techniques and molecular simulation technologies. The results showed that Bai/Gen/Isl exhibited strong inhibitory activity against AMY with IC 50 values of 22.44 ± 0.92 μmoL·L −1 , 24.78 ± 1.91 μmoL·L −1 , and 26.78 ± 1.79 μmoL·L −1 , respectively, which belonged to the mixed inhibition type dominated by competitive inhibition. The three form a ground state complex with AMY through a static quenching mechanism, and the order of binding constants is Bai > Gen > Isl. Their binding significantly changed the microenvironment polarity of Trp residues in AMY and induced secondary structure rearrangement. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) showed that the relative crystallinity of AMY increased, forming dense aggregates and increasing thermal stability. Molecular simulation showed that the interactions between AMY and Bai/Gen were dominated by van der Waals forces or hydrogen bonds, while the interactions with Isl were dominated by hydrophobic interactions. By employing a novel integrative approach combining fluorescence/UV–Vis/FTIR spectroscopy, DSC-XRD-SEM characterization, and 120 ns molecular dynamics simulation, this study overcomes the single-technique limitations of previous research and provides a theoretical basis for the development of blood glucose control agents based on natural products.
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