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Polyphyllin I promotes cell death via suppressing UPR-mediated CHOP ubiquitination and degradation in non-small cell lung cancer

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Chinese Journal of natural medicines 2021年第4期19卷 255-266页

作者： LIU Ming-Ming ZHU Miao-Lin DONG Rui-Fang ZHANG Chao ZHANG Hao YANG Lei KONG Ling-Yi XIA Yuan-Zheng Jiangsu Key Laboratory of Bioactive natural Product research and State Key Laboratory of natural medicines China Pharmaceutical UniversityNanjing 210009China Jiangsu Cancer Hospital Nanjing 210009China

Polyphyllin I(PPI)purified from Polyphylla rhizomes displays puissant cytotoxicity in many kinds of *** researches investigated its anti-cancer *** novel mechanisms are still worth *** study aimed to explore PPI-induced endoplasmic reticulum(ER)stress as well as the underlying mechanism in non-small cell lung cancer(NSCLC).Cell viability or colony-forming was detected by MTT or crystal violet *** cycle,apoptosis,reactive oxygen species(ROS)and mitochondrial membrane potential were assessed by flow *** and protein levels were evaluated by q RT-PCR and immunoblotting *** interaction was determined by immunoprecipitation or immunofluorescence *** overexpression or silencing was carried out by transient transfection with plasmids or small interfering *** Cancer Genome Atlas(TCGA)database was used for Gene Set Enrichment Analysis(GSEA),survival analysis,gene expression statistics or pathway enrichment *** inhibited the propagation of NSCLC cells,increased non-viable apoptotic cells,arrested cell cycle at G2/M phase,induced ROS levels but failed to decrease mitochondrial membrane *** levels of GRP78 indicates poor prognosis in NSCLC *** selectively suppressed unfolded protein response(UPR)-induced GRP78 expression,subsequently protected CHOP from GRP78-mediated ubiquitination and *** demonstrated that the natural product PPI,obtained from traditional herbal medicine,deserves for further study as a valuable candidate for lead compound in the chemotherapy of NSCLC.

关键词： Non-small cell lung cancer Polyphyllin I Endoplasmic reticulum stress C/EBP homologous protein Ubiquitination

Lignans with(N,N-diethyl)methyl amino group from Buxus rugulosa

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Chinese Journal of natural medicines 2021年第9期19卷 675-679页

作者： WANG Yu-Huan YIN Yong CUI Le-Tian LI Qiu-Rong KONG Ling-Yi LUO Jun Jiangsu Key Laboratory of Bioactive natural Product research and State Key Laboratory of natural medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China

Buxrugulosides A–E,four lignan glycosides(1–4)and a protocatechuate derivative(5)featuring a rare(N,Ndiethyl)methyl amino group at aromatic rings,were obtained from the aerial parts of Buxus rugulosa,which is famous for treating coronary heart *** structures including absolute configurations were elucidated by HRMS,1 D and 2 D NMR,and by comparing their CD data with previous *** 1 was a rare sesquilignan,and all of these compounds were the first example of lignans with(N,N-diethyl)methyl amino group.

关键词： Lignan glycoside (N,N-diethyl)methyl amino group Buxus rugulosa

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H:quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase

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Chinese Journal of natural medicines 2024年第1期22卷 75-88页

作者： SONG Jiangzhou ZOU Guiqing ZHAO Zhou ZHU Ya XUE Jiayu AO Lanjia SUN Huiyong HAO Haiping ZHANG Bo XU Xiaowei State Key Laboratory of natural medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China State Key Laboratory of natural medicines China Pharmaceutical UniversityNanjing 210009China

NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavin protease highly expressed in various cancer ***1 catalyzes a futile redox cycle in substrates,leading to substantial reactive oxygen species(ROS)*** ROS generation results in extensive DNA damage and elevated poly(ADP-ribose)polymerase 1(PARP1)-mediated consumption of nicotinamide adenine dinucleotide(NAD^(+)),ultimately causing cell *** phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD^(+)salvage synthesis pathway,emerges as a critical target in cancer *** concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+*** this study,we designed,synthesized,and assessed a novel series of proqodine A derivatives targeting both NQO1 and *** these,compound T8 demonstrated potent antitumor ***,T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and *** discovery offers a promising new molecular entity for advancing anticancer research.

关键词： NQO1 ROS NAMPT NAD^(+) T8

Identification of active compound combination contributing to anti-inflammatory activity of Xiao-Cheng-Qi Decoction via human intestinal bacterial metabolism

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Chinese Journal of natural medicines 2018年第7期16卷 513-524页

作者： LIU Xing-Yan LI Li LI Xue-Qing YU Bo-Yang LIU Ji-Hua Jiangsu Key Laboratory of TCM Evaluation and Translational research China Pharmaceutical University State Key Laboratory of natural medicines China Pharmaceutical University

Human intestinal bacteria play an important role in the metabolism of herbal medicines, leading to the variations in their pharmacological profile. The present study aimed to investigate the metabolism of Xiao-Cheng-Qi decoction(XCQD) by human intestinal bacteria and to discover active component combination(ACC) contributing to the anti-inflammatory activity of XCQD. The water extract of XCQD was anaerobically incubated with human intestinal bacteria suspensions for 48 h at 37 °C. A liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry(LC-Q-TOF/MS) method was performed for identification of the metabolites. In addition, the anti-inflammatory effects of XCQD and biotransformed XCQD(XCQD-BT) were evaluated in vitro with cytokines in RAW264.7 cells induced by lipopolysaccharide(LPS). A total of 51 compounds were identified in XCQD and XCQD-BT. Among them, 20 metabolites were proven to be transformed by human intestinal bacteria. Significantly, a combination of 14 compounds was identified as ACC from XCQD-BT, which was as effective as XCQD in cell models of inflammation. In conclusion, this study provided an applicable method, based on intestinal bacterial metabolism, for identifying combinatory compounds responsible for a certain pharmacological activity of herbal medicines.

关键词： Xiao-Cheng-Qi decoction Human intestinal bacteria Metabolism Anti-inflammatory LC-Q-TOF/MS

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

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Neural Regeneration research 2025年第1期20卷 242-252页

作者： Daiyu Hu Yuanqing Cao Chenglin Cai Guangming Wang Min Zhou Luying Peng Yantao Fan Qiong Lai Zhengliang Gao Fundamental research center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Institute of Geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)Shanghai University School of MedicineNantongJiangsu ProvinceChina Shanghai Engineering research center of Organ Repair Shanghai University School of MedicineShanghaiChina Key Laboratory of Arrhythmias Ministry of EducationShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Human brain development is a complex process,and animal models often have significant *** address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and *** enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid *** involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid *** cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology *** a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental *** organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature *** exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic *** convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

关键词： cadmium cell death cell proliferation cortical development environmental toxins neural progenitor cells neurogenesis neurotoxicology organoids stem cells

Rapid identification of stigmastane-type steroid saponins from Vernonia amygdalina leaf based onα-glucosidase inhibiting activity and molecular networking

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Chinese Journal of natural medicines 2022年第11期20卷 846-853页

作者： GAO Juanjuan ZHAO Mengling SHAN Shujun LI Yongyi LUO Jun LI Yi School of Food Science and Pharmaceutical Engineering Testing&Analysis CenterNanjing Normal UniversityNanjing 210023China Jiangsu Key Laboratory of Bioactive natural Product research and State Key Laboratory of natural medicines China Pharmaceutical UniversityNanjing 210009China

Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines,especially Vernonia amygdalina,a famous nature medicine for the treatment of tonsillitis,diabetes,*** current study was designed to combine molecular networking(MN)with diagnostic ions for rapid identification ofΔ^(7,9(11))stigmastane-type saponins which were theα-glucosidase inhibitory active substances in ***,theα-glucosidase inhibitory activities of fiveΔ^(7,9(11))stigmastane-type steroid saponins that were previously isolated were screened,which indicated that theΔ^(7,9(11))stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating ***,a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN,MolNetEnhancer and unsupervised substructure annotation(MS2LDA).Based on this strategy,other sevenΔ^(7,9(11))stigmastane-type steroid saponins were identified from this *** research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of *** leaf.

关键词： Δ^(7,9(11))Stigmastane-type steroid saponins α-Glucosidase inhibitory activity Fragmentation pathways Diagnostic ions Molecular networking

Fast-onset antidepressant targeting the nNOS-SERT interaction in the DRN

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Chinese Journal of natural medicines 2023年第1期21卷 1-2页

作者： GUAN Xin PANG Tao State Key Laboratory of natural medicines New Drug Screening CenterChina Pharmaceutical UniversityNanjing 210009China

Major depressive disorder is one of the most deleterious mental disorders with a high suicide rate,incidence and recurrence rate,which is manifested as continuous depression,retardation of thinking as well as loss of ... 详细信息

关键词： Depression nNOS SERT Antidepressant Fast-onset

Red cell distribution width/platelet ratio predicts decompensation of metabolic dysfunction-associated steatotic liver disease-related compensated advanced chronic liver disease

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World Journal of Gastroenterology 2025年第3期31卷 1-10页

作者： Ming-Hua Zheng Amedeo Lonardo Department of Hepatology MAFLD Research CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Internal Medicine Azienda Ospedaliero-Universitaria of Modena(2023)Modena 41126Italy

Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical *** paper published by Dallio et al reports on red cell distribution width(RDW)/platelet ratio(RPR)as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease(MASLD)-related *** from other biomarkers and algorithms,RPR is inexpensive and widely available,based on parameters which are included in a complete blood *** is computed on the grounds of two different items,one of which,RDW,mirrors the host’s response to a variety of disease stimuli and is *** second parameter involved in RPR,platelet count,is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for *** disease is the primary cause of mortality among MASLD subjects,followed by extra-hepatic cancers and liver-related ***,MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic *** sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.

关键词： Cirrhosis Liver fibrosis natural course Prognostication Stratification

Collaborative assembly-mediated siRNA delivery for relieving inflammation-induced insulin resistance

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Nano research 2020年第11期13卷 2958-2966页

作者： Shiyang Shen Li Zhang Mengru Li Zhizi Feng Huixia Li Xiao Xu Shiqi Lin Ping Li Can Zhang Xiaojun Xu Ran Mo State Key Laboratory of natural medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Advanced Pharmaceuticals and BiomaterialsChina Pharmaceutical UniversityNanjing210009China

Obesity plays a primary causative role in insulin resistance and hyperglycemia that contributes to type 2 *** lipid storage in the liver renders activation of the resident macrophages and chronic secretion of inflammatory mediators,therefore causing or aggravating insulin ***,we develop collaborative assemblies using a“one-pot”synthesis method for macrophage-specific delivery of small interfering RNAs(siRNAs)that target the inflammatory *** nanocomplex(NC)composed of the siRNA molecule,a synthetic thiol-bearing methacrylated hyaluronic acid(sm-HA)and protamine forms through an electrostatic-driven physical assembly,which is chemically crosslinked to acquire the collaboratively assembled nanocapsule(cNC)*** obtained cNC displays significantly higher stability than *** moieties as flexible assembly units can be easily equipped on cNC for long circulation,active targeting,or controlled siRNA ***-F decorated with folic acid,a macrophage-targeting ligand promotes the siRNA accumulation in the activated macrophages in the liver of the obese mouse ***-F loaded with siRNA targeting inflammatory indicators efficiently control the macrophage inflammatory response by reducing the expression of the inflammatory proteins(>40%reduction)and ameliorating the insulin resistance symptoms of the obese mice.

关键词： small interfering RNA(siRNA)delivery collaborative assembly nanomedicine insulin resistance diabetes