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isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells

Chinese Medical Journal 2023年第18期136卷 2210-2220页

作者： Zeyu Wang Weijian Li Xue Wang Qin Zhu Liguo Liu Shimei Qiu Lu Zou Ke Liu Guoqiang Li Huijie Miao Yang Yang Chengkai Jiang Yong Liu Rong Shao Xu’an Wang Yingbin Liu Department of Biliary-Pancreatic Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Shanghai Research Center of Biliary Tract Disease Shanghai 200092China Shanghai Lung Tumor Clinical Medical Center Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong UniversitySchool of MedicineShanghai 200092China University of Shanghai for Science and Technology School of Medical Instrument and Food EngineeringShanghai 200093China Department of General Surgery Changzhou Hospital of Traditional Chinese Medicine Nanjing University of Chinese MedicineChangzhouJiangsu 213004China Department of Pharmacology Shanghai Jiao Tong University School of MedicineShanghai 200025China

Background:Gallbladder cancer(GBC)is the most common malignant tumor of biliary ***(ISL)is a natural compound with chalcone structure extracted from the roots of licorice and other *** studies have shown that ISL has a strong anti-tumor ability in various types of ***,the research of ISL against GBC has not been reported,which needs to be further ***:The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test,RNA-sequencing,quantitative real-time polymerase chain reaction,reactive oxygen species(ROS)detection,lipid peroxidation detection,ferrous ion detection,glutathione disulphide/glutathione(GSSG/GSH)detection,lentivirus transfection,nude mice tumorigenesis experiment and ***:ISL significantly inhibited the proliferation of GBC cells in *** results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC,and HMOX1 and GPX4 were the key molecules of ISL-induced *** of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC ***,ISL significantly reversed the iron content,ROS level,lipid peroxidation level and GSSG/GSH ratio of GBC ***,ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and ***:ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and downregulating GPX4 in vitro and in *** evidence may provide a new direction for the treatment of GBC.

关键词： isoliquiritigenin Ferroptosis Gallbladder cancer HMOX1 GPX4

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isoliquiritigenin suppresses microglial activation and neuroinflammation in primary microglia

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中国药理学与毒理学杂志 2016年第10期30卷 1024-1024页

作者： FU Yan YANG Pin ZHAO Yang XU Ying Department of Physiology Shanghai University of Traditional Chinese Medicine

OBJECTIVE Microglial activation contributes to neuroinflammation and neuronal damages in neurodegenerative disorders including Alzheimer and Parkinson *** has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be ***(ISL)isolated from Glycyrrhiza glabra possess potent anti-inflammatory capability,we thus investigate the inhibitory effects of ISL on LPS-induced microglial activation and neuroinflammation and the roles of neuroprotection on neurodegenerative ***,we would explore the mechanism of itsassociated inflammatory signaling *** By cultivating,isolating and purifying,we got the primary microglia of the *** form of those cells was observed under an optical microscope,the purity was identified by the CD11b immunefluorescence ***,the effects of ISL on microglial viability were explored by the MTT *** microglial cells were pretreated by ISL(5μmol·L-1)and then stimulated by LPS(100 ng·mL-1),the production of NO was detected by Griess reagent,the change of microglial morphology was observed by immunefluorescence *** production of IL-1βand TNF-αin culture medium were tested by ELISA,and the m RNA expression of pro-inflammatory factors,including IL-1β,TNF-α,i NOS and COX-2 was detected by real time *** protein expression of i NOS and COX-2was detected by Western ***(1)After purifying,microglial showed the typical morphological *** cell body was small,protruding outstretched in the branch rod,*** LPS stimulation,the shape was changed to amoeba-like,and the protrusions retracted,cell *** the CD11b immunefluorescence staining,the purity of the microglial was over 98%,and showed powerful phagocytic activity.(2)The results show that ISL(0.16-20μmol·L-1)concentration has no effect on primary microglia′s *** at the concentration of 5μmol·L-1ISL has the significantly inhibitory effect on NO

关键词： isoliquiritigenin primary microglia inflammatory factors neuroinflammation

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Metallothionein mediates cardioprotection of isoliquiritigenin against ischemia-reperfusion through JAK2/STAT3 activation

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Acta Pharmacologica Sinica 2006年第11期27卷 1431-1437页

作者： Wei AN Jing YANG~1 Ying AO Department of Pharmacology,School of Medicine,Wuhan University,Wuhan 430071,China DepartmentofPharmacology SchoolofMedicineWuhanUniversityWuhan430071China

Aim:To examine whether isoliquiritigenin(ISL)can attenuate myocardial ischemia-reperfusion(MI/R)injury in rats by inducing metallothionein(MT)through acti-vation of janus kinase 2(JAK 2)/signal transducers and activators of transcription3(STAT 3)***:The experimental model of MI/R in rats was gener-ated by 30 min of ischemia and reperfusion for 2 *** mRNA expression of MT,COX-2,and iNOS were measured by *** protein expressions of MT,JAK/STAT,extracellular signal-regulated kinase(ERK),and Akt were determinedby Western blotting in the absence or presence of a JAK kinase inhibitor,tyrphostinAG490(1.0 mg/kg,iv,1h before ischemia).Results:Pretreatment with ISL mark-edly decreased the severity of reperfusion-induced arrhythmias and myocardialinfarct *** the ISL 20 mg/kg group,the activities of lactate dehydrogenase(LDH)and creatinine phosphokinase(CPK)were reduced by 38.4% and 51.3%when compared with the vehicle *** JAK 2/STAT 3 phosphoryla-tion was accompanied by increased synthesis of MT but not of COX-2 or iNOS inISL-treated ***490 can significantly weaken ISL-induced cardioprotectionand prevent the increase of MT expression and JAK 2/STAT 3 ***:ISL protected MI/R injury through activation of JAK 2/STAT 3 sig-nal transduction pathway,which might be involved in mediating the upregulationof MT expression.

关键词： isoliquiritigenin myocardial ischemiareperfusion metallothionein janus kinase STAT3 transcription factors

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isoliquiritigenin Inhibits Microglial Activation and Neuroinflammation

Isoliquiritigenin Inhibits Microglial Activation and Neuroin...

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中国神经科学学会第十二届全国学术会议

作者： Yan Fu Ying Xu Department of Physiology Shanghai University of Traditional Chinese Medicine

Introduction Microglial activation contributes to neuroinflammation and neuronal damages in neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled. isoliquiritigenin（ISL） isolated from Glycyrrhiza glabra possess potent anti-inflammatory capability, we thus investigate the effect of ISL on LPS-induced microglial activation and neuroinflammation. Objective The aim of this research is to observe the effects of ISL on microglial activation and neuroinflammation. Methods We identify the effects of ISL on microglial cell viability by MTT test. NO product generation was tested by Griess assay after induced by LPS（100 ng/ml） and treated by ISL. The changed forms of cells were observed by immunofluorescence and the levels of IL-1β and TNF-α were tested by ELISA method. The m RNA expression of i NOS and COX2 were detected by Real time PCR and their protein levels were tested by western blotting. Result The over-activation of primary microglia induced by LPS was obviously receded by ISL treatment. And the NO product generation was reduced by ISL in a dose-dependent（P＜0.05）. We find that ISL could decrease the m RNA level and protein concentration of TNF-α after LPS stimulated（P＜0.05）. ISL could significantly lessen IL-1β concentration in ELISA experiment（P＜0.05）. The protein expression of i NOS and COX2 can be remarkably reduced by ISL（P＜0.05）. Conclusion ISL can obviously inhibit the over-activation of microglia and reduce neuroinflammation by decreasing levels of pro-inflammatory factors.

关键词： isoliquiritigenin microglia neuroinflammation pro-inflammatory factors

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Anticancer activity of isoliquiritigenin: biological effects and molecular mechanisms

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Journal of Chinese Pharmaceutical Sciences 2019年第10期28卷 673-686页

作者： Wenxiu Xin Qilu Fang Jiao Sun Sisi Kong Lingya Chen Ping Huang Department of Pharmacy Zhejiang Cancer HospitalHangzhou 310022China

Natural compounds derived from plants have attracted considerable attention in the scientific community due to their nontoxic nature and anti-cancer ***(ISL),an active flavonoid isolated from the root of the licorice plant(Glycyrrhiza uralensis),has been previously demonstrated to have anti-inflammatory,antioxidant and tumor suppressive *** the past few years,the number of studies describing the effects of ISL against cancer has been gradually *** has been found to inhibit viability,proliferation,and migration of cancer cells mainly through cell cycle arrest,induction of apoptosis as well as ***,the molecular mechanisms of action are not completely *** review aimed to provide a comprehensive summary of the biological effects and molecular mechanisms of ISL against cancer.

关键词： Cancer isoliquiritigenin Effect Mechanism

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Interaction of isoliquiritigenin with bovine serum albumin studied by fluorescence quenching method

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Journal of Chinese Pharmaceutical Sciences 2016年第3期25卷 196-200页

作者：韩博龙飞于玮陈文王新春郭刚周良学石河子大学药学院新疆石河子832002 四川大学生物治疗国家重点实验室四川成都610041

Interaction of ioliquiritigenin（ISL）, which is the main active component of a commonly used traditional Chinese medicine（TCM） Glycyrrhiza uralensis Fisch. with bovine serum albumin（BSA） has been investigated. The quenching mechanism of fluorescence of bovine serum albumin by ISL was discussed. The binding sites number n and apparent binding constant K were measured by fluorescence quenching method. The thermodynamic parameters ΔH^0, ΔG^0, ΔS^0 at different temperatures were calculated. The distance r between donor（bovine serum albumin） and acceptor（ISL） was obtained according to F？rster theory of non-radiation energy transfer. The results of synchronous fluorescence spectra and UV-vis absorption spectra show that the conformation of bovine serum albumin has been changed.

关键词： isoliquiritigenin Bovine serum albumin Thermodynamic parameters Energy transfer

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Pharmacological Mechanism of isoliquiritigenin Antitumor

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Medicinal Plant 2019年第1期10卷 17-18页

作者： Hui XUE Jiaru WANG Wanting XU Yi ZHANG Yinghua LUO Chenghao JIN College of Life Science and Technology Heilongjiang Bayi Agricultural University

isoliquiritigenin could play an antitumor role by inhibiting proliferation of tumor cells, inducing apoptosis of tumor cells and resisting neovascularity. In this paper, antitumor activity and mechanism of isoliquirit... 详细信息

关键词： isoliquiritigenin Antitumor activity Cell proliferation Apoptosis

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Effects of isoliquiritigenin on Proliferation,Apoptosis and NF-κB Signaling Pathway in Human Lung Cancer H460 Cells

Effects of Isoliquiritigenin on Proliferation,Apoptosis and ...

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第十四届中国中西医结合基础理论学术年会

作者： YUEMU QIN ZEQUN JIANG YANXIA MA XU ZHANG School of Medicine and Life Sciences Nanjing University of Chinese Medicine Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor Nanjing University of Chinese Medicine

To study the effect of isoliquiritigenin(ISL) on the proliferation,cell cycle and apoptosis of human lung cancer cell line NCI-H460,and to explore its relevant molecular mechanism to provide a new scientific basis for lung cancer ***-H460 cells in logarithm growth phase were selected and cultured with different concentration of *** cell viability was detected by CCK-8 assay,while cell cycle and cell apoptosis were measured by cytometry *** mRNA expression of lung cancer related genes in NCI-H460 cells were determined by PCR *** protein levels of p-p65,IKB α,IKB β,Bax and Bcl-2 were detected by Western blot ***,the effect of ISL on the expression of NF-κB p65 was observed by immunofluorescence *** results showed that ISL could inhibit proliferation and induce cell cycle block,as well as cell apoptosis in NCI-H460 *** mechanism may be related with the inhibition of the NF-κB signaling pathway,by inhibiting the entry of NF-κB p65 into the nucleus,it failing to exert its transcriptional activity and ultimately affecting the expression of downstream apoptotic proteins Bax and Bcl-2.

关键词： isoliquiritigenin lung cancer NCI-H460 cell apoptosis NF-κB

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Adsorption and desorption of isoliquiritigenin and liquiritigenin to carbon nanotubes

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Journal of Chinese Pharmaceutical Sciences 2010年第6期19卷 443-450页

作者：赵海娇慕春海李超鹏韩博王新春陈文新疆特种植物药资源教育部重点实验室新疆石河子832000

The adsorption and desorption of isoliquiritigenin and liquiritigenin to different types of carbon nanotubes （CNTs） were comparatively studied in this study. The pore structure, specific surface area, surface morphologies and functional groups of the CNTs were tested by N2 adsorption, scanning electron microscope （SEM） and infrared spectra （IR）. The investigation of dynamic adsorption, isothermal equilibrium adsorption and desorption of isoliquiritigenin and liquiritigenin to CNTs demonstrated that the adsorption amount on oxidized multi-walled carbon nanotubes （o-MWCNTs） was greater than that on raw multi-walled carbon nanotubes （r-MWCNTs）, especially the adsorption of isoliquiritigenin to o-MWCNTs. The data of equilibrium adsorption were better represented by the Freundlich isotherm model. In addition, the adsorbed amount per unit CNTs was decreased when the temperature got higher. From the results of isothermal equilibrium adsorption and desorption to CNTs, it could be inferred that o-MWCNTs had higher adsorption to isoliquiritigenin and liquiritigenin than r-MWCNTs. Additionally, o-MWCNTs had a better desorption efficiency to isoliquiritigenin and liquiritigenin （about 48.57% and 32.86%） than r-MWCNTs （about 24.56% and 17.46%）.

关键词： Carbon nanotubes isoliquiritigenin Liquiritigenin Adsorption and desorption

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Multidimensional screening of Astragalus membranaceus small molecules to mitigate carbon ion radiation-induced bystander effects

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药物分析学报（英文版） 2024年第10期14卷 1531-1534页

作者： Liying Zhang Yiming Zhang Yangyang Li Qiyang Li Shangzu Zhang Zhiming Miao Jinpeng He Ting Zhou Gengqiang Yang Xin Wang Jufang Wang Yongqi Liu Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese MedicineLanzhou73000China Gansu Institute of Cardiovascular Diseases Lanzhou730000China Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and the Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and Universities Gansu University of Chinese MedicineLanzhou73000China Key Laboratory of Space Radiobiology of Gansu Province & Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences Institute of Modern PhysicsChinese Academy of SciencesLanzhou730000China Gansu Institute of Cardiovascular Diseases Lanzhou730000China

Existing studies have shown that Astragalus membranaceus(AM)and its active ingredients astragalus polysaccharides,oninon,and astragalus methyl glycosides can attenuate X-ray radiation-induced ***,there are no studies on how isoliquiritigenin(ISL)attenuate the bystander effect of bone marrow mesenchymal stem cells(BMSCs)induced by carbon ion radiation therapy for lung *** study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect(RIBE)in BMSCs to elucidate its mecha-nism of *** this study,we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro,and the models were successfully treated with carbon *** further work,we used flow cytometry,immunofluorescence,Western blot,enzyme-linked immunosorbent assay(ELISA),inhibitor,short hairpin RNA(shRNA),Cell Counting Kit-8(CCK-8),and other methods to illustrate the *** the next experiments,we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation *** aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo *** Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung *** results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.

关键词： Radiotherapy BMSCs HIF-1α Astragalus membranaceus isoliquiritigenin Non-small cell lung

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