RSC Advances
·
2016
·Vol. 6
·期 89
·86640-86649
·
IF 3.289
Mingyan Liao,Yudan Zhao,Lizi Huang,Biao Cheng,Kun Huang
Parkinson's disease (PD), with widespread aggregation of α-synuclein in the form of Lewy bodies as a neuropathological hallmark, is a rising threat for ageing society. Glycyrrhiza uralensis is an herbal medicine and sweets used for centuries in Asia and Europe, its major pharmacologically active ingredients include isoliquiritigenin (ILG), liquiritin (LT), liquiritigenin (LG) and glycyrrhizic acid (GA). Here, we investigated the effects of Glycyrrhiza uralensis ethanol extract (GUE) and the above four compounds, on the aggregation of α-synuclein in vitro and in a transgenic Caenorhabditis elegans PD model NL5901. In vitro, ILG, LT and GUE inhibit the amyloid formation of α-synuclein and alleviate the toxicity caused by aggregates; moreover, ILG could disaggregate preformed fibrils. In vivo, ILG, LT and GUE not only reduce amyloid formation in C. elegans NL5901, but also extend its life span. Together, these data suggest that ILG and LT may be further considered as candidates for PD treatment.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2014
·
IF 2.829
Feng Chen,Hai-Long Li,Yin-Feng Tan,Yong-Hui Li,Wei-Yong Lai,Wei-Wei Guan,Jun-Qing Zhang,Yuan-Sheng Zhao,Zhen-Miao Qin
Alpinia oxyphylla (Yizhi) capsularfruits are commonly used in traditional medicine. Pharmacological studies have demonstrated that A. oxyphylla capsularfruits have some beneficial roles. Besides volatile oil, sesquiterpenes, diarylheptanoids and flavonoids are main bioactive constituents occurring in the Yizhi capsularfruits. The representative constituents include tectochrysin, izalpinin, chrysin, apigenin-4′,7-dimethylether, kaempferide, yakuchinone A, yakuchinone B, oxyphyllacinol and nootkatone. Their content levels in the fruit and its pharmaceutical preparations have been reported by our group. The nine phytochemicals are also the major components present in the Yizhi alcoholic extracts, which have anti-diarrheal activities. However, the fates of these constituents in the body after oral or intravenous administration remain largely unknown. In the present study, we focus on these phytochemicals albeit other concomitant compounds. The chemicals and their metabolites in rat plasma were identified using liquid chromatography/tandem mass spectrometry with selected reaction monitoring mode after orally administered Yizhi extract to rats. Rat plasma samples were treated by methanol precipitation, acidic or enzymatic hydrolysis. This target analysis study revealed that: (1) low or trace plasma levels of parent chemicals were measured after p.o. administration of Yizhi extract, Suoquan capsules and pills to rats; (2) flavonoids and diarylheptanoids formed mainly monoglucuronide metabolites; however, diglucuronide metabolites for chrysin, izalpinin and kaempferide were also detected; (3) metabolic reduction of Yizhi diarylheptanoids occurred in rats. Yakuchinone B was reduced to yakuchinone A and then to oxyphyllacinol in a stepwise manner and subsequently glucuronidated by UDP-glucuronosyl transferase. Further research is needed to characterize the UDP-glucuronosyl transferase and reductase involved in the biotransformation of Yizhi chemicals.
研究领域:
药理学
·
分析化学
✓ 已验证
DOI
高影响因子
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.
研究领域:
水产养殖学
·
病毒学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
Reproductive and Developmental Medicine
·
2022
·Vol. 6
·期 2
·104
·
IF 0
Li Zhi,Liu Yan,Liu Hai-Ou,Wu Zhi-Yong,Xu Cong-Jian,Zhang Fei-Fei
Objective: Altered bile acid transformation induces low-grade chronic inflammation and may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). Liquiritincan regulate bile acid metabolism and anti-inflammatory properties; however, limited information is available regarding its therapeutic potential in PCOS. Methods: Female C57BL/6 mice were randomly assigned into four groups ( n = 6 mice/group): the control, letrozole or dehydroepiandrosterone-induced PCOS groups, PCOS + 20 mg/kg liquiritin group, and control + liquiritin groups. After 21 days of treatment, the mice were euthanized, and the associated metabolism indications were investigated. Ovarian histological examinations were performed, and serum hormone concentration was measured. The expression of key genes involved in steroid hormone synthesis, ovarian follicle development, and ovulation was assessed. Results: Liquiritin reduced fasting blood glucose levels and increased insulin sensitivity compared to the PCOS group. Liquiritin also significantly decreased serum levels of total testosterone ( P < 0.001) and dehydroepiandrosterone sulfate ( P < 0.05) in the PCOS group. Histomorphological inspection of ovaries from the liquiritin group revealed fewer cystic dilated follicles than in the PCOS group. Moreover, liquiritinsignificantly ( P < 0.01) decreased Cyp17a1, Cyp19a1, Fshr, Hsd3b2, Runx2 , and Ccn2 mRNA expression compared to letrozole-induced PCOS. Conclusion: Liquiritin may be safe and helpful in ameliorating PCOS-associated hyperandrogenemia and hyperglycemia. However, clinical trials investigating different liquiritin dosages are needed to confirm these findings.
研究领域:
内分泌学
·
药理学
✓ 已验证
DOI
Nature Chemical Biology
·
2025
·
IF 13.7
Xie Jiali,Tian Jiayu,Khan Salman,Chen Feilong,Yu Jingwei,Hao Yuqiong,Xiong Hao-Ming,Zhang Feng,Zhou Qian,Zhu Guo-Yuan,Huang Ancheng C.
Glyceollins are structurally complex potent antimicrobial isoflavonoid phytoalexins produced by the crop soybean ( Glycine max ), yet their biosynthesis remains elusive, making it impossible to carry out synthetic biology-based production and engineering for further development. Here, via assembling synergistic engineering strategies, we successfully rewired the metabolic fluxes in Nicotiana benthamiana leaves for high-yield production of isoflavonoid precursor daidzein (7.04 g kg −1 dry weight (dw)), allowing for efficient screening and identification of six cytochrome P450 monooxygenases, namely glyceollin synthases, that furnish the pyrano/furano E ring and complete the 15-step biosynthetic pathways of diverse glyceollins. We establish that purified glyceollins are important for plant defense as they can effectively suppress the growth of Phytophthora sojae in vitro. Our engineered plant chassis can provide facile access to bioactive isoflavonoids, as manifested by the de novo total biosynthesis of glyceollins (for example, I, II, III and VII at up to 5.9 g kg −1 , dw) and medicarpin (0.72 g kg −1 , dw) for enhanced pathogen resistance and medicinal value.
研究领域:
植物学
·
代谢工程
·
合成生物学
·
药用植物
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
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.
研究领域:
心血管医学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Plants-Basel
·
2020
·Vol. 9
·期 2
·245
·
IF 2.762
Shuang Zhang,Shi-Wei Sun,Hai-Lin Shi,Ke Zhao,Jin Wang,Yang Liu,Xiao-Hong Liu,Wei Wang
Isoliquiritigenin, a natural chalcone-type flavonoid, has been recognized as an allelochemical with phytotoxicity to lettuce; however, not enough attention has been paid to the mechanisms of this secondary metabolite. In this work, we investigated the physiological and biochemical mechanisms of isoliquiritigenin on lettuce seedlings. The results show that isoliquiritigenin has a concentration-dependent inhibitory effect on radicle elongation of lettuce seedlings, but no significant impact on lettuce germination. Microscopy analyses suggest that the surface morphology of lettuce radicle tips was atrophied and the intracellular tissue structure deformed at high concentrations. Isoliquiritigenin induced the overproduction of reactive oxygen species (ROS), which led to loss of cell viability in the radicle cells. In addition, malondialdehyde (a product of lipid peroxidation) and free proline levels were found to have increased, while chlorophyll content in lettuce seedlings decreased. All these changes suggest that the primary allelopathic mechanism of isoliquiritigenin by which it inhibits radicle elongation in lettuce seedlings might be due to the overproduction of ROS, which causes oxidative damage to membrane lipids and cell death.Keywords:isoliquiritigenin;phytotoxicity;Lactuca sativa;reactive oxygen species;cell viability;lipid peroxidation
研究领域:
植物学
·
生理学
·
生化与分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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.
研究领域:
生物化学
·
药物化学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2015
·Vol. 16
·期 8
·17999-18017
·
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
研究领域:
药学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Jian Liu,Qilong Wang,Michael Adu-Frimpong,Qiuyu Wei,Yujiao Xie,Kangyi Zhang,Chunmei Wei,Wen Weng,Hao Ji,Elmurat Toreniyazov,Ximing Xu,Jiangnan Yu
Isoliquiritigenin (ISL) has a great variety of pharmacological effects especially liver cancer therapy, but its poor solubility, bioavailability and liver targeting have limited its clinical use. In order to solve the aforementioned shortcomings, the TPGS-modified proliposomes loaded with ISL (ISL-TPGS-PLP) was prepared in this study. ISL-TPGS-PLP was fabricated via thin-film dispersion method and was characterized by the appearance, particle size, zeta potential and morphology. HPLC was used to evaluate entrapment efficiency (EE), in vitro release and stability of ISL-TPGS-PLP single or combined while appropriate physicochemical parameters were measured with DLS . Meanwhile, the pharmacokinetics and tissue distribution were also studied after oral administration. The results demonstrated that ISL-TPGS-PLP had a mean size of 23.8 ± 0.9 nm , high EE of 97.33 ± 0.40%. More importantly, nearly 90% ISL was released from ISL-TPGS-PLP within 24 h while only 50% was released from ISL suspension. In the pharmacokinetics study, the area under the curve (AUC 0-24h) of ISL-TPGS-PLP was 1.53 times higher than that of ISL suspension. The Tissue distribution study showed that the ISL released from ISL-TPGS-PLP was higher in the liver than the free ISL suspension. Altogether, ISL-TPGS-PLP could ameliorate the ISL solubility, bioavailability and liver targeting ability, suggesting that ISL-TPGS-PLP could serve as a promising nanocarrier for liver cancer therapy.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 7
·3898-3915
·
IF 5.882
Li Zhang,Sheng-Ye Yang,Feng-Rong Qi-Li,Xiao-Xiao Liu,Wei-Tao Zhang,Chao Peng,Ping Wu,Ping Li,Pingping Li,Xiaojun Xu
Isoliquiritigenin (ISO) is a flavonoid extracted from the root of licorice, which serves various biological and pharmacological functions including antiinflammatory, antioxidation, liver protection, and heart protection. However, the mechanism of its action remains elusive and the direct target proteins of ISO have not been identified so far. Through cell-based screening, we identified ISO as a potent lipid-lowering compound. ISO treatment successfully ameliorated fatty acid-induced cellular lipid accumulation and improved nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by increasing PPARα-dependent lipid oxidation and decreasing SREBPs-dependent lipid synthesis. Both these signaling required the activation of SIRT1. Knockdown of SIRT1 resulted in the reversal of ISO beneficiary effects suggesting that the lipid-lowering activity of ISO was regulated by SIRT1 expression. To identify the direct target of ISO, limited proteolysis combined with mass spectrometry (LiP-SMap) strategy was applied and IQGAP2 was identified as the direct target for ISO in regulating lipid homeostasis. In the presence of ISO, both mRNA and protein levels of SIRT1 were increased; however, this effect was abolished by blocking IQGAP2 expression using siRNA. To explore how IQGAP2 regulated the expression level of SIRT1, proteome profiler human phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that ISO affected. We found that through phosphorylation of CREB, ISO transduced signals from IQGAP2 to upregulate SIRT1 expression. Thus, we not only demonstrated the molecular basis of ISO in regulating lipid metabolism but also exhibited for the first time a novel IQGAP2-CREB-SIRT1 axis in treating NAFLD/NASH.
研究领域:
药理学
·
分子生物学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Qin Zhou,Yishi Wei,Yijing Liao,Xing Hu,Deming Gong,Guowen Zhang
Identification of new α -glucosidase ( α -Glu) inhibitors from natural sources is very important to the management of type 2 diabetes. In this work, liquiritigenin (LTG), a flavonoid compound derived from liquorice, was found to have excellent inhibition of α -Glu (IC 50 = 27.91 ± 3.48 μM) in a mixed manner. LTG reduced the endogenous fluorescence of α -Glu in a static mode by spontaneously forming stable complexes with the α -Glu-substrate through hydrophobic forces and hydrogen bonding. LTG decreased the α -helix and β -sheet contents of α -Glu while increasing the β -turn and random coil contents. Computer simulation showed that LTG interacted non-covalently with Gly161, Glu422, Glu429, and Asn235 residues of α -Glu, causing structural unfolding of the enzyme, which affected the substrate-enzyme interaction and ultimately reduced the release of the product. While acarbose, a competitive inhibitor of α -Glu, spontaneously hydrogen-bonded Tyr158, His280, Asp242, and Asp352 residues of the LTG− α -Glu complex. Moreover, a combination of LTG (6.00 μM) and acarbose (30.00 μM) had a remarkable synergistic inhibition on α -Glu, which may be because LTG made the structure of α -Glu loosening and reduced its catalytic activity through allosteric effect. And the occupation of the active cavity by acarbose may lead to a conformational change in the LTG− α -Glu complex, which effectively hindered the binding between the substrate and α -Glu. These findings may offer a new theoretical foundation for the development of LTG as a glucose-lowering ingredient in functional foods.
研究领域:
药理学
·
生物化学
·
计算生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）