Food Bioscience
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2026
·
IF 6.2
Jingwen Li,Hossain M. Zabed,Yufei Zhang,Junhua Yun,Yuehui Tian,Guoyan Zhang,Xianghui Qi
Liquiritigenin (LIG) is a natural flavonoid with diverse bioactivities, rendering it attractive for applications in food, pharmaceuticals, nutraceuticals, and cosmetics. However, its de novo biosynthesis in microbial hosts faces several major challenges, including the lack of efficient enzymes compatible with heterologous systems, insufficient supply of precursor amino acids, suboptimal cofactor availability and electron transfer efficiency. To evaluate these constraints, Saccharomyces cerevisiae was engineered through systematic stepwise comparison of p -coumaric acid-forming routes, downstream enzyme sources, aromatic amino acids precursor supply, NADPH availability, and fermentation conditions. The best-performing strain QL14 produced 4.09 mg/L LIG in shake-flask fermentation and 8.42 mg/L LIG in 5-L fed-batch fermentation. However, naringenin (NAR) remained the predominant downstream product. These results indicate that increased pathway input improved overall flavanone output but was insufficient to redirect flux toward the CHR-dependent LIG-forming branch. Therefore, downstream branch selectivity, rather than precursor or NADPH supply alone, represents the major constraint in the current yeast system. This work provides a basis for future CHR-focused engineering and controllable LIG/NAR co-production.
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Cell Reports
·
2026
·Vol. 45
·期 2
·
IF 7.7
Luhang Dai,Guo Cheng,Tingting Cui,Sitong He,Ran Wang,Jingqi Kang,Pei Li,Xin Zhang,Xiaoli Ding,Xiaochang Xue,Luting Yang,Yaling Zhang,Yaping Yan
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease of the central nervous system (CNS) that, despite overlapping phenotypic features with multiple sclerosis (MS), manifests with more severe clinical outcomes. The defining pathogenic driver of NMOSD is the aquaporin-4 (AQP4) autoantibody, which induces astrocytic injury via complement-dependent cytotoxicity (CDC). MS is predominantly managed with disease-modifying therapies (DMTs) such as interferon-beta (IFN-β) to reduce relapse rates. However, these therapies are often ineffective or even detrimental in NMOSD. Our findings demonstrate that while IFN-β mitigates experimental autoimmune encephalomyelitis (EAE), it exacerbates NMOSD-like astrocytopathy. Deleting IFNAR1 counteracts this effect by selectively enhancing astrocyte activation without altering other CNS cells. Subsequently, we characterized multiple MS therapeutics that paradoxically worsen NMOSD-like pathology, whereas agents promoting astrocytic activation confer protection. Collectively, we establish a framework for astrocyte-centered drug screening and underscore the therapeutic potential of targeting astrocytes in NMOSD, connecting fundamental disease mechanisms to clinical applications.
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INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY
·
2026
·
IF 3.6
Hui Yu,Nan Wang,Changjiang Sun,Bingfeng Leng,Liping Sun,Xuming Deng,Lei Xu,Zihao Teng,Jianfeng Wang,Lin Wang
Enterotoxigenic Escherichia coli (ETEC), a predominant pathogen responsible for neonatal animal diarrhea, poses a significant threat to global health and results in considerable economic losses in animal husbandry. The pathogenicity of ETEC is primarily mediated by its adherence to intestinal epithelial cells via fimbriae adhesins and the subsequent secretion of enterotoxins. We developed a high-throughput screening platform for chorionic inhibitors. By employing semi-solid motility assays, hemagglutination inhibition assays, and cell adhesion assays, we screened a panel of natural compounds and identified Isogliquiritin (ISL) as the active compound. Subsequent validation using transmission electron microscopy and reverse transcription-polymerase chain reaction (qRT-PCR) revealed that ISL significantly inhibits the synthesis and assembly of ETEC fimbriae, thereby reducing bacterial adhesion to host cells. After assessing its safety, we demonstrated through in vivo experiments that ISL attenuates ETEC-induced diarrhea. In the Galleria mellonella larval model, ISL increased the survival rate, meanwhile in a mouse diarrhea model, ISL reduced inflammation caused by ETEC C83902 and upregulated the expression of tight junction protein (ZO-1, claudin-1, and occluding) genes. Collectively, our findings highlight that ISL is a promising natural compound for the prevention and treatment of ETEC-induced diarrhea. By targeting bacterial virulence factors rather than bacterial growth, ISL provides a novel strategy against antimicrobial resistance and offers a safer alternative for managing ETEC infections in livestock.
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ENVIRONMENTAL TOXICOLOGY
·
2023
·Vol. 38
·期 3
·654-665
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IF 4.5
Yufang Su,Lei Fang,Kaili Zhong,Ting Wang,Mingjie Bao,Ting Zhou,Yuan Zhu
Isoliquiritigenin (ISL) is used in many households' personal hygiene and medicinal products, and the average human daily ISL exposure is 1–2 mg/kg. However, the molecular mechanisms of ISL toxicity in zebrafish embryos have not been fully elucidated. We investigated whether exposure to ISL induces oxidative stress and inflammatory responses in zebrafish. And exposure to ISL significantly affects the expression of immune response-related genes in zebrafish embryos following oxidative stress and the release of pro-inflammatory mediators through Toll-like receptor signaling.
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Frontiers in Pharmacology
·
2023
·
IF 5.6
Zhang Xiuying,Chen Qilei,Zhao Jia,Zhao Wei,Fan Ni,Wang Yu,Chen Hubiao,Rong Jianhui
Myocardial infarction (MI) is a highly prevalent and lethal disease worldwide. Prevention and timely recovery are critical for the control of the recurrence and heart failure in MI survivors. The present study was designed to investigate the cardioprotective activity of the herbal medicine formula Baoyuan Decoction (BYD) and identify the active compounds and molecular targets. The ethanolic BYD extract (BYDE) was prepared by water extraction and ethanol precipitation of four herbal medicines, Astragali Radix, Ginseng Radix et Rhizoma, Cinnamomi Cortex, and Glycyrrhizae Radix et Rhizoma. Initially, BYDE was validated for the cardioprotective effectiveness in a mouse model of ischemia injury and rat cardiomyocyte H9C2 cells. As results, BYDE effectively reduced infarct size from 56% to 37% and preserved cardiac functions in mouse MI model while protected H9C2 cells against oxygen glucose deprivation. Subsequent network pharmacology analysis revealed that 122 bioactive ingredients, including flavonoids and saponins from the UPLC-MS/MS profile of BYDE, might target 37 MI-related proteins, including inflammatory and apoptotic mediators (e.g., TNF, NFKB1, CASPs, TNFRSF1A, CXCL12, BCL2A1). Pathway enrichment analysis suggested that BYDE might control the cardiac inflammation via targeting the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB) pathway while the selected targets were also implicated in IL-17 signaling pathway, lipid and atherosclerosis. Consequently, adenosine, ginsenoside Rh2, isoliquiritigenin, and licochalcone A were selected to generate the four-compound mixture AGILe and validated for the inhibitory effects on the TNF-α/NF-κB pathway. The results of the present study suggested that the mixture AGILe might be a potential cardioprotective remedy against MI.
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Bioengineering-Basel
·
2022
·Vol. 9
·期 8
·382
·
IF 5.046
Jianman Wang,Hongjin Chen,Tao Guo,Ping Yue,Tianbao Qian,Xiangyu Zeng,Yali Luo,Jiangmin Li,Lijing Teng,Qingyu Liu,Liang Hong,Zijiang Yu,Zuquan Hu
Isoliquiritigenin (ILQ) has a number of biological activities such as antitumor and anti-inflammatory effects. However, biomedical applications of ILQ are impeded by its poor aqueous solubility. Therefore, in this research, we prepared a novel ILQ-loaded nanoemulsion, i.e., ILQ-NE, which consisted of Labrafil®M 1944 CS (oil), Cremophor®EL (surfactant), ILQ, and phosphate-buffered saline, by employing a combined sonication (high-energy) and phase-inversion composition (low-energy) method (denoted as the SPIC method). The ILQ-NE increased the ILQ solubility ~1000 times more than its intrinsic solubility. It contained spherical droplets with a mean diameter of 44.10 ± 0.28 nm and a narrow size distribution. The ILQ loading capacity was 4%. The droplet size of ILQ-NE remained unchanged during storage at 4 °C for 56 days. Nanoemulsion encapsulation effectively prevented ILQ from degradation under ultraviolet light irradiation, and enhanced the ILQ in vitro release rate. In addition, ILQ-NE showed higher cellular uptake and superior cytotoxicity to 4T1 cancer cells compared with free ILQ formulations. In conclusion, ILQ-NE may facilitate the biomedical application of ILQ, and the SPIC method presents an attractive avenue for bridging the merits and eliminating the shortcomings of traditional high-energy methods and low-energy methods.Keywords:isoliquiritigenin;nanoemulsion;sonication;phase-inversion composition (PIC)
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Liangwan Wei,Zhe Wang,Yindi Chu,Kun Cai,Wei Li,Piying Huang,Youcai Qin,Dailin Liu,Xiaocui Zhuang,Mingquan Guo,Xinbo Song,Enguo Fan
Antimicrobial resistance (AMR) crisis urges the development of new antibiotics. In the present work, we for the first time used bio-affinity ultrafiltration combined with HPLC-MS (UF-HPLC-MS) to examine the interaction between the outer membrane β-barrel proteins and natural products. Our results showed that natural product licochalcone A from licorice interacts with BamA and BamD with the enrichment factor of 6.38 ± 1.46 and 4.80 ± 1.23, respectively. The interaction was further confirmed by use of biacore analysis, which demonstrated that the Kd value between BamA/D and licochalcone was 6.63/28.27 μM, suggesting a good affinity. To examine the effect of licochalcone A on BamA/D function, the developed versatile in vitro reconstitution assay was used and the results showed that 128 μg/mL licochalcone A could reduce the outer membrane protein A integration efficiency to 20%. Although licochalcone A alone can not inhibit the growth of E. coli , but it can affect the membrane permeability , suggesting that licochalcone A holds the potential to be used as a sensitizer to combat AMR.
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JOURNAL OF MOLECULAR STRUCTURE
·
2021
·
IF 3.196
Xiangrong Li,Hongyi Liu,Zhenhua Yang,Hanxiao Duan,Ziyang Wang,Zeqing Cheng,Zhizhi Song,Xinzhe Wu
In this study, the binding of baicalin, liquiritin and isoliquiritigenin to hyaluronidase (HAase) was investigated by computational modeling approaches as well as steady state fluorescence, time-resolved fluorescence and circular dichroism (CD) spectroscopy. The molecular docking results reveal that the three flavonoids bind in the internal cavity of HAase. The catalytic activity of amino acid residues near the binding site indicates that HAase activity will be inhibited by the three flavonoids. The results of molecular docking and thermodynamic analysis show that hydrophobic interaction, electrostatic force and hydrogen bond are the main interaction forces. Fluorescence data reveal that the fluorescence quenching mechanism of HAase by the three flavonoids is all static quenching procedure. The binding affinity is strongest for baicalin and ranks in the order baicalin >i soliquiritigenin > liquiritin. The binding energy values for the interaction of HAase with baicalin, liquiritin and isoliquiritigenin are -26.634 kJ mol −1 , -23.762 kJ mol −1 and -25.929 kJ mol −1 at 298.15 K, respectively. Synchronous fluorescence spectroscopy indicates that the addition of baicalin and liquiritin increases the polarity and decreases the hydrophobicity of HAase around Trp-and/or Tyr. The addition of isoliquiritigenin has no significant effect on the microenvironment of Trp-and Tyr-of HAase. The results of CD show that the binding of the three flavonoids with HAase leads to changes in the secondary structure of HAase.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
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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Foods
·
2019
·Vol. 8
·期 9
·355
·
IF 3.011
Chengyun He,Xiaoling Liu,Zhaojing Jiang,Sheng Geng,Hanjun Ma,Benguo Liu
Flavonoids are known to play a role in hypoglycemia by inhibiting α-glucosidase. However, their interaction mechanism with α-glucosidase still needs to be elaborated. In this study, the α-glucosidase inhibitory activities of 15 flavonoids were investigated. Their molecular volume had a negative effect on inhibitory activity, while the number of phenolic hydroxyl groups on the B ring was positively correlated with inhibitory activity. To explain the significant differences in activity, the interaction behaviors of myricetin and dihydromyricetin, which have similar structures, were compared by spectrofluorimetry, molecular docking, and the independent gradient model (IGM). In the fluorescence analysis, myricetin exhibited a higher binding capacity. Based on molecular docking and IGM analysis, their non-covalent interactions with α-glucosidase could be visualized and quantified. It was found that they had different binding modes with the enzymes and that myricetin possessed stronger hydrogen bonding and van der Waals force interactions, which explained the thermodynamic results.Keywords:flavonoids;α-glucosidase;interaction;molecular docking;independent gradient model
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Frontiers in Pharmacology
·
2018
·
IF 3.831
Zhang Man,Wu Yan-Qing,Xie Ling,Wu Jiang,Xu Ke,Xiao Jian,Chen Da-Qing
Severe acute pancreatitis (SAP) is a digestive system disease that is associated with a range of complications including intestinal dysfunction. In this study, we determined that the chalcone compound, isoliquiritigenin (ISL), reduces pancreatic and intestinal injury in a mouse model of SAP. These effects were achieved by suppressing oxidative stress and the inflammatory responses to SAP. This was evidenced by a reduction in histological score, and malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor (TNF)-α and cleaved-caspase-3 (c-caspase-3) protein along with an increase in Nrf2, hemeoxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), and superoxide dismutase (SOD). We then used Nrf2-/- mice to test the protective effect of Nrf2 during ISL treatment of SAP. Our results indicated that Nrf2-/- mice had greater pancreatic injury and intestinal dysfunction than wild-type mice. They also had reduced adherens junctions (P120-catenin) and tight junctions (occludin), and increased activated nuclear factor-κB (NF-κB) protein. In Nrf2-/- mice, ISL was less effective at these functions than in the WT mice. In conclusion, this study demonstrated that ISL exerts its protective effects against oxidative stress and inflammatory injury after SAP via regulation of the Nrf2/NF-κB pathway. It also showed that the efficacy of ISL in repairing the intestinal barrier damage caused by SAP is closely related to the Nrf2 protein. Our findings demonstrated that Nrf2 is an important protective factor against SAP-induced injuries in the pancreas and intestines.
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JOURNAL OF LUMINESCENCE
·
2013
·
IF 2.144
Jie-hua Shi,Jing Wang,Ying-yao Zhu,Jun Chen
The intermolecular interaction between isoliquiritigenin (ISL) and bovine serum albumin (BSA) under imitated physiological conditions was investigated using fluorescence, circular dichromism (CD) and molecular docking methods. The results revealed that the fluorescence quenching of BSA at 338 nm by ISL resulted from the formation of ISL–BSA complex. The number of binding sites ( n ) for ISL binding on BSA was approximately equal to 1. The experimental and molecular docking results revealed that after binding ISL to BSA, ISL was close to Tyr residue than Trp residue , the binding of ISL to BSA induced a slight change in conformation of BSA but the BSA still retains its secondary structure, the binding process of ISL with BSA is spontaneous, and ISL could be inserted into the hydrophobic cavity of BSA (Site I) in the binding process of ISL with BSA. The enthalpic change (Δ H 0 ) and entropic change (Δ S 0 ) in the process of interaction of BSA with ISL were –116.74 kJ mol –1 and –286.32 J mol –1 K –1 , respectively, indicating that the main interaction forces of ISL with BSA were Van der Waals and hydrogen bonding interactions. And, it can be suggested from the molecular docking results that the flexibility of ISL plays an important role in increasing the stability of the whole system upon association of ISL with BSA.
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