Artificial Cells Nanomedicine and Biotechnology
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2020
·
IF 3.343
Gang Wang,Yang Yu,Yu-Zhu Wang,Pei-Hao Yin,Ke Xu,Heng Zhang
In this study, isoliquiritigenin (ISL) incorporated nanoliposomes were prepared and their effects on colorectal cancer (CRC) cell lines were investigated. Herein, we sought to explore the anti-cancer mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Also, the key targets such as caveolin 1 (CAV1), glucose transporters and Akt/mTOR that promote glycolysis, and are activated via the induction of α-enolase (ENO1), fructose bisphosphate aldolase A (ALDOA) and monocarboxylate transporter 4 (MCT4) expressions were also investigated. It was shown that ISL-NLs significantly suppressed the proliferation and glucose uptake of CRC cell by potentially regulating the glycolysis and lactate targets as well as pathways that formed the basis of the anti-CRC effects of ISL-NLs. The mechanism underlying this effect was further validated via the regulation of some key targets such as ENO1, ALDOA, lactate dehydrogenase A (LDHA) and MCT4 in glycolysis coupled with cellular myelocytomatosis oncogene (c-myc), hypoxia-inducible factor 1-alpha (HIF-1α) in protein kinase B/mTOR (Akt/mTOR) pathways. Moreover, the AMPK proteins were identified to be up-regulated while the lactic acid production was suppressed by ISL-NLs in the CRC cells, indicating that ISL-NLs had an inhibitory effect on AMPK mediated glycolysis and lactate production. Altogether, these results have provided insights into the mechanism underlying the key role that liposomal ISL played in the multiple inhibition of AMPK and Akt/mTOR mediated glycolysis and lactate generation, which may be regulated as the alternative metabolic pathways of CRC as well as serve as adjuvant therapy for the disease.
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Cell Death & Disease
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2020
·Vol. 11
·期 12
·1-14
·
IF 6.304
Huang Xiaozhong,Shi Yujuan,Chen Hongjin,Le Rongrong,Gong Xiaohua,Xu Ke,Zhu Qihan,Shen Feixia,Chen Zimiao,Gu Xuemei,Chen Xiaojun,Chen Xiong
Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.
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AAPS PHARMSCITECH
·
2019
·Vol. 20
·期 5
·1-11
·
IF 2.608
Zhang Kangyi,Wang Qilong,Yang Qiuxuan,Wei Qiuyu,Man Na,Adu-Frimpong Michael,Toreniyazov Elmurat,Ji Hao,Yu Jiangnan,Xu Ximing
The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35 nm), negative zeta potential (− 10.67 ± 0.86 mV), and high encapsulation efficiency (98.17 ± 0.24%). The in vitro release study indicated that the release rates of the formulation were obviously higher in different release media (HCl, pH 1.2; PBS, pH 6.8; double-distilled water, pH 7.0) compared with the ISL solution. The oral bioavailability of the ISL-SMEDDS was enhanced by 4.71 times in comparison with the free ISL solution. More importantly, ISL-SMEDDS significantly reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in the model rats. Collectively, the prepared ISL-SMEDDS proved to be potential carriers for enhancing the solubility and oral bioavailability of ISL, as well as ameliorating its anti-hyperuricemic effect.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Kumar Ganesan,Cong Xu,Chunguang Xie,Yue Sui,Chuan Zheng,Fei Gao,Jianping Chen
Breast cancer (BC) is the most common cancer in women and is known for its tendency to spread to the bones, causing significant health issues and mortality. In this study, we aimed to investigate whether cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles (ISL@ZLH NPs) could inhibit BC-induced bone destruction and tumor metastasis in both in vitro and animal models. To evaluate the potential of ISL@ZLH NPs, we conducted various experiments. First, we assessed cell viability, colony formation, transwell migration, and wound healing assays to determine the impact of ISL@ZLH NPs on BC cell behavior. Western blotting, TRAP staining and ALP activity were performed to examine the effects of ISL@ZLH NPs on osteoclast formation induced by MDA-MB-231 cell-conditioned medium and RANKL treated RAW 264.7 cells. Furthermore, we assessed the therapeutic impact of ISL@ZLH NPs on tumor-induced bone destruction using a mouse model of BC bone metastasis. Treatment with ISL@ZLH NPs effectively suppressed BC cell proliferation, colony formation, and motility, reducing their ability to metastasize. ISL@ZLH NPs significantly inhibited osteoclast formation and the expression of factors associated with bone destruction in BC cells. Additionally, ISL@ZLH NPs suppressed JAK-STAT signaling in RAW264.7 cells. In the BCBM mouse model, ISL@ZLH NPs led to a significant reduction in osteolytic bone lesions compared to the control group. Histological analysis and TRAP staining confirmed that ISL@ZLH NPs preserved the integrity of bone structure, preventing invasive metastasis by confining tumor growth to the bone marrow cavity. Furthermore, ISL@ZLH NPs effectively suppressed tumor-induced osteoclastogenesis, a key process in BC-related bone destruction. Our findings demonstrate that ISL@ZLH NPs have the potential to inhibit BC-induced bone destruction and tumor metastasis by targeting JAK-STAT signaling pathways and suppressing tumor-induced osteoclastogenesis. These results underscore the therapeutic promise of ISL@ZLH NPs in managing BC metastasis to the bones.
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Journal of Functional Foods
·
2023
·
IF 5.6
Lina Jian,Huixing Wu,Haiyan Zeng,Ting Quan,Fan Xia,Shijian Xiang,Benjie Zhou
The therapeutic and pharmacological potential of isoliquiritigenin has been reported in relieving inflammation and lipid metabolism disorders, particularly in the context of non-alcoholic fatty liver disease (NAFLD). The aim of this study is to investigate the effects of isoliquiritigenin on NAFLD, obesity-associated metabolic symptoms in vivo and in vitro , and explore new mechanisms underlying its effects. Our study revealed that isoliquiritigenin effectively reduced lipid accumulation and suppressed inflammation factors expression in hepatocytes and high fat diet (HFD) mice. Additionally, it prevented body weight gain and liver damage in HFD mice. Importantly, RNA-sequencing results revealed that isoliquiritigenin exerts its anti-NAFLD effect may through the mTOR pathway and autophagy. Rescue experiments further confirmed that it inhibits inflammation by suppressing the PI3K/AKT/mTOR pathway and reduces lipid accumulation by promoting autophagy. Therefore, it holds promise as a novel treatment for NAFLD.
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International Journal of Nanomedicine
·
2020
·
IF 5.115
Mingzhuo Cao,Mengling Zhan,Zheng Wang,Zeqian Wang,Xiu-Min Li,Mingsan Miao
Purpose Isoliquiritigenin (ILQ), an important component of Anti-Asthma Herbal Medicine Intervention (ASHMI), had shown potent anti-asthma effect in vitro in our previous study. However, poor solubility and low bioavailability hindered in vivo application to treat asthma. This study was to develop a novel ILQ loaded self-nanoemulsifying drug delivery system (ILQ-SMEDDS) with enhanced bioavailability. Methods The optimized SMEDDS formulation was composed of ethyl oleate (oil phase), Tween 80 (surfactant) and PEG400 (co-surfactant) at a mass ratio of 3:6:1. The physiochemical properties of ILQ-SMEDDS, including drug content, globule size, zeta potential, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, were characterized. And the in vitro release profile, in situ intestinal absorption, in vivo pharmacokinetic parameters and the anti-asthma effect of ILQ suspension and ILQ-SMEDDS were evaluated. Results The ILQ-SMEDDS had an average globule size of 20.63 ± 1.95 nm with a polydispersity index (PDI) of 0.11 ± 0.03, and its zeta potential was −12.64 ± 2.12 mV. The cumulative release rate of ILQ from ILQ-SMEDDS to the simulated gastrointestinal tract was significantly higher than that of free ILQ suspension. And area under curve with ILQ-SMEDDS was found to be 3.95 times higher than that of ILQ suspension indicating improved bioavailability by SMEDDS. Although ILQ-SMEDDS showed a slight less effective inhibitory effect on eotaxin-1 in human lung fibroblast (HFL-1) cells than free ILQ, in an ovalbumin-induced asthma model, ILQ-SMEDDS exhibited more efficacy than ILQ suspension in improving asthma-associated inflammation, including eosinophil production, ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 4 (IL 4), interleukin 5 (IL 5) and interferon-γ (IFN-γ). Even the low dose of ILQ-SMEDDS group (10 mg/kg) showed better anti-asthma effect than that of the ILQ suspension group (20 mg/kg). Conclusion Compared with ILQ suspension, ILQ-SMEDDS showed significantly improved bioavailability and anti-asthma effect, revealing its potential as a favorable pharmaceutical agent for treating asthma.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2020
·Vol. 24
·期 17
·9667-9681
·
IF 4.486
Li-Juan Wang,Lin He,Lu Hao,Hong-Lei Guo,Xiang-Peng Zeng,Ya-Wei Bi,Guo-Tao Lu,Zhao-Shen Li,Liang-Hao Hu
Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone-type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein-induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF-κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti-inflammatory and anti-fibrotic therapeutic agent for CP.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Deshan Yao,Liuxiang Bao,Sichuan Wang,Meng Tan,Yuanyuan Xu,Tianxu Wu,Zhengang Zhang,Kaizheng Gong
Ischemia-reperfusion (I/R) injury, a multifaceted pathological process, occurs when the prolongation of reperfusion duration triggers ferroptosis-mediated myocardial damage. Isoliquiritigenin (ISL), a single flavonoid from licorice, exhibits a wide range of pharmacological impacts, but its function in ferroptosis caused by myocardial I/R injury remains unclear. This study delved into the protective effect of ISL on myocardial I/R injury-induced ferroptosis and its mechanism. Neonatal mouse cardiomyocytes (NMCM) underwent hypoxia/reoxygenation (H/R) to simulate the pathological process of myocardial I/R. ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage. CCK8 experiment revealed that the ferroptosis inhibitor Ferrostatin-1 significantly improved myocardial cell viability after 24 h of reoxygenation, and ISL treatment showed a similar effect. ISL reduced intracellular free iron accumulation, up-regulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, and inhibited lipid peroxidation accumulation, thereby alleviating ferroptosis. The Nrf2-specific inhibitor ML385 counteracted ISL's defensive role against H/R-triggered oxidative stress damage and ferroptosis. In vivo experiments further confirmed that by regulating the translocation of Nrf2 into the nucleus, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4, Drp1 to exert the antioxidant role, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R. ML385 nearly abolished ISL's protective impact on the I/R model by inhibiting Nrf2 function. In summary, ISL is capable of mitigating oxidative stress, mitochondrial damage, and cardiomyocyte ferroptosis caused by I/R, thereby reducing myocardial injury. A key mechanism includes triggering the Nrf2/HO-1/SLC7A11/GPX4 pathway to prevent oxidative stress damage and cardiomyocyte ferroptosis caused by I/R.
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AQUACULTURE
·
2024
·
IF 3.9
Tian-Xiu Qiu,Lei Liu,Xu Zhang,Yang Hu,Jiong Chen
Isoliquiritigenin, a flavonoid from Glycyrrhiza glabra , demonstrates potent antiviral properties by enhancing host defenses through antioxidative and immunomodulatory mechanisms. Our in vitro data demonstrate that isoliquiritigenin significantly inhibits spring viremia of carp virus (SVCV) at concentrations up to 100 μg/ml without inducing cytotoxicity, effectively reducing viral replication and the production of new viral particles. Treatment with isoliquiritigenin markedly reduced the cytopathic effects in EPC cells, improving cell viability by more than 50 %. Furthermore, isoliquiritigenin enhances resistance to SVCV infection by significantly reducing intracellular the viral load when cells are pretreated for up to 24 h. This inhibition primarily occurs during the viral replication and assembly phases, without affecting viral binding or entry. Additionally, isoliquiritigenin strengthens antioxidant defenses and modulates immune responses, thereby reducing oxidative damage and interferon production. In vivo experiments with juvenile carp corroborate the antiviral efficacy of isoliquiritigenin, showing significantly reduced mortality rates and the viral load in SVCV-infected fish. These findings highlight the potential of isoliquiritigenin as an antiviral agent in aquaculture, providing a sustainable alternative to traditional chemotherapeutics by concurrently inhibiting viral replication and enhancing host immune defenses.
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CHROMATOGRAPHIA
·
2024
·
IF 1.2
Liu Yijie,Zhang Dan,Bai Ligai,Yan Hongyuan,Liu Haiyan
In this paper, a mixed-mode monolith was prepared by separately synthesizing hydrophilic and hydrophobic materials at both ends of a chromatography column by a one-step method. The prepared mixed mode monolith was used as solid phase extraction adsorbent for simultaneous enrichment and purification of licorice chalcone A and isoliquiritigenin from licorice combined with high performance liquid chromatography (HPLC). It had superior ability to enrich and purify licorice chalcone A and isoliquiritigenin than single hydrophilic or hydrophobic monolith. The method had good linearity in the range of 0.50–400 μg/mL. The linear regression equation was y = 465.45 × − 1.04 and the correlation coefficient was 0.9999. The relative standard deviations (RSDs) of intra-day and inter-day precision were both less than 1.19%. The results showed that the method was simple and accurate, and could be used for the enrichment and purification of licorice chalcone A and isoliquiritigenin from licorice.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Kaihan Li,Can Zhao,Kunshan Wang,Hongyu Liang,Suzhen Zhou,Jinbo Fan
β-Lg can simultaneously load and protect the three flavonoid compounds, namely Isl, Gen, and Bai. • In terms of stability, the β-Lg-multilinked compound shows a better protective effect against the three types of flavonoids. • A spectroscopic approach was adopted to elucidate the binding mechanisms of three flavonoids with β-Lg. • The conformational characteristics of the complexes were investigated through molecular docking and dynamics simulations. This study elucidates the interaction mechanisms of Isoliquiritigenin (Isl), Genistein (Gen) and Baicalein (Bai) with β-lactoglobulin (β-Lg), with a focus on the protein's capacity for the co-encapsulation and stabilization of these flavonoids. The binding mechanisms were characterized using fluorescence spectroscopy, high-performance liquid chromatography, non-radiative energy transfer analysis, molecular simulations. The results demonstrated that the binding affinity ( K a ) followed the order Bai > Gen > Isl. Accordingly, the calculated binding distances for Isl, Gen and Bai were 5.36 nm, 4.49 nm, and 4.20 nm, respectively. β-Lg is capable of co-encapsulating two or three flavonoids simultaneously. The most stable ternary complex (β-Lg-Isl-Gen-Bai) formed when the flavonoids were added in the sequence of Bai, Isl, and then Gen. The β-Lg multi-ligand complex provided superior protection for Isl, Gen, and Bai compared to their respective single-ligand complexes across all tested parameters: stability, antioxidant capacity, and α-amylase inhibition. For Isl, the retention rate improvement under storage stability is the largest, reaching 73.86 ± 1.04%; for Gen, the retention rate improvement under light stability is the largest, reaching 75.22 ± 0.77%; and for Bai, the retention rate improvement under thermal stability is the largest, reaching 71.90 ± 1.02%. β-Lg simultaneously encapsulates and stabilizes three flavonoids Isl, Gen, Bai, serves as a natural and potent protein carrier for these bioactive compounds, and offers theoretical support for their protection against degradation.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
·
IF 5.062
Yan Wang,Chen Zhang,Meng Xiao,Kumar Ganesan,Fei Gao,Qingqing Liu,Zhen Ye,Yue Sui,Feng Zhang,Kunhua Wei,Yaobin Wu,Jianmin Wu,Bing Du,Cong Xu,Yan Li,Peng Li,Jinming Zhang,Jianping Chen
Treatment of aggressive triple-negative breast cancer (TNBC) is still challenging. Isoliquiritigenin (ISL) is a water-insoluble bioactive compound possessing high anti-TNBC capacity with less toxicity. The present study aimed to develop a safe and effective oral drug delivery system to improve the oral efficacy of ISL for TNBC therapeutics. ISL-loaded zein phosphatidylcholine hybrid nanoparticles ( [email protected] NPs) were constructed by a one-step solvent evaporation method. Optimization and characterization of [email protected] NPs were performed. Cellular uptake in vitro and biodistribution of ZLH NPs in vivo were investigated. The pharmacokinetics of [email protected] NPs in terms of ISL content in the plasma, organs, and tumor tissues were validated, and the anti-TNBC efficacy was evaluated. Encapsulation efficiency (96.75 ± 1.41%) and drug loading efficiency (6.56 ± 0.83%) were found in [email protected] NPs. [email protected] NPs were able to enhance the absorption of ISL in the tumor sites. Moreover, the upregulation of p27 and downregulation of EGFR and CDK4 were observed in [email protected] NPs treated tumors. Collectively, oral intake of [email protected] NPs would be translated into a potential clinical therapy strategy against TNBC.
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