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The delivery of N-myc downstream-regulated gene 2(NDRG2)self-amplifying mRNA via modified lipid nanoparticles as a potential treatment for drug-resistant and metastatic cancers

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Medical Review 2024年第3期4卷 235-238页

作者： Sandra E.Reznik Amit K.Tiwari Vivek Chavda Charles R.Ashby Jr. Department of pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensUSA Departments of Pathology and Obstetrics and Gynecology and Women’s Health Montefiore Medical Center/Albert Einstein College of MedicineBronxUSA Department of pharmaceutical Sciences College of Pharmacy University of Arkansas for Medical Sciences Little RockUSA Department of Pharmaceutics and pharmaceutical Technology L.M.college of Pharmacy AhmedabadIndia Department of pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA

The protein,N-myc downstream-regulated gene 2(NDRG2),a tumor suppressor,is significantly decreased or absent in many types of *** is a significant negative correlation between the levels of NDRG2 and the development and progression of cancer tumor recurrence and tumor invasion,in different *** contrast,the in vitro and in vivo overexpression of the NDRG2 protein decreases the proliferation,growth,adhesion and migration of many types of cancer *** in vitro overexpression of NDRG2 increases the efficacy of certain anticancer drugs in specific types of cancer *** hypothesize that the delivery of the mRNA of the NDRG2 protein,encapsulated by lipid nanoparticles,could represent a potential treatment of metastatic and drug-resistant *** would be accomplished using a self-amplifying mRNA that encodes the NDRG2 protein and an RNA-dependent-RNA polymerase,obtained from an in vitrotranscribed(IVT)*** IVT mRNA would be encapsulated in a lipid *** efficacy of the nanoformulation would be determined in cultured cancer cells and if the results are positive,nude mice transplanted with either drug-resistant or metastatic drug-resistant cancer cells,would be treated with the nanoformulation and monitored for efficacy and adverse *** the appropriate preclinical studies indicate this formulation is efficacious and safe,it is possible it could be evaluated in clinical trials.

关键词： N-myc downstream-regulated gene 2(NDRG2) cancer self-amplifying mRNA nanoparticle

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Asymmetric Synthesis of Dihydrospirotryprostatin B via a Silica Gel-Mediated Cyclization of Tryptamine-Ynamide

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Chinese Journal of Chemistry 2024年第12期42卷 1355-1359页

作者： Changhong Han Lu Yang Kaizong Yao Sen Zhang Jiayue Fu Hanyang Sun Hongsheng Xu Bin Lin Maosheng Cheng Yongxiang Liu Key Laboratory of Structure:Based Drug Design and Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China Wuya college of Innovation Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China Institute of Drug Research in Medicine Capital of China BenxiLiaoning 117000China Zhejiang Shapuaisi pharmaceutical Co. LtdPinghuZhejiang 314299China

Comprehensive Summary An asymmetric synthesis of dihydrospirotryprostatin B was achieved in 15 steps(8 purifications)from *** main feature of our synthetic strategy is the efficient construction of spirocyclic oxindole intermediate containing a chiral quaternary carbon center,involving the silica gel-mediated cyclization of tryptamine-ynamide and oxidation under neat conditions.

关键词： Asymmetric synthesis Alkaloids Dihydrospirotryprostatin B Tryptamine-ynamide Cross-coupling Silica gel-mediated cyclization Oxidation

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Structure-guided isolation of anti-neuroinflammatory sesquiterpene coumarins from Ferula sinkiangensis

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Chinese Journal of Natural Medicines 2024年第7期22卷 643-653页

作者： DANG Wen GUO Tingting ZHOU Di MENG Qingqi FANG Mingxia CHEN Gang LIN Bin HOU Yue LI Ning School of Traditional Chinese Materia Medica Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning ProvinceKey Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110016China college of Life and Health Sciences Northeastern UniversityShenyang 110004China School of pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

The resin of Ferula sinkiangensis has been traditionally utilized for treating gastrointestinal disorders,inflammation,tumors,various cancers,and alopecia *** primary bioactive constituents,sesquiterpene coumarins,have demonstrated notable therapeutic potential against *** this study,a structure-guided fractionation method was used to isolate nine novel sesquiterpene coumarins from the resin of *** compounds were characterized and structurally elucidated using comprehensive physicochemical and spectroscopic techniques,including calculated electronic circular dichroism(ECD).Anti-neuroinflammatory assays revealed that compounds 2,3,and 6 significantly inhibited nitric oxide(NO)production in lipopolysaccharide(LPS)-stimulated BV2 microglial cells,with IC_(50)values ranging from 1.63 to 12.25μmol·L^(−1).

关键词： Ferula sinkiangensis Sesquiterpene coumarins Structure elucidation Anti-neuroinflammatory activity

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ROS-responsive nanoparticles targeting inflamed colon for synergistic therapy of inflammatory bowel disease via barrier repair and anti-inflammation

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Nano Research 2024年第6期17卷 5409-5423页

作者： Ding Wang Qi Jiang Ruoyu Shen Lijun Peng Wentao Zhou Tingting Meng Fuqiang Hu Jianwei Wang Hong Yuan college of pharmaceutical Science Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009China

The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological *** studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease(IBD).Oral administration is the most common route for intestinal *** this study,a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment,which can interrupt the pathological process of IBD,resulting in the significantly improved efficacy of existing *** on the specific pH values and high reactive oxygen species(ROS)levels in inflammatory sites of IBD,an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed,and confirmed in vitro and in *** anti-inflammatory drug dexamethasone acetate(Dex)and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions(TJs).The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with *** brief,a drug delivery system and a therapeutic strategy for IBD are successfully developed.

关键词： nanotechnology reactive oxygen species(ROS)-responsive targeted delivery inflammatory bowel disease(IBD) intestinal barrier combination treatment

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Dammarane-type triterpenoids from Gynostemma longipes and their protective activities on hypoxia-induced injury in PC12 cells

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Chinese Journal of Natural Medicines 2024年第5期22卷 466-480页

作者： LIANG Haizhen CHEN Xiaojuan LI Qi ZHANG Mengmeng LU Pengxin ZHANG Jie SONG Juan ZHANG Tao GUO Baolin MA Baiping Department of pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China AnKang Chia Tai pharmaceutical Co. Ltd.Shaanxi 725000China

Sixteen new dammarane-type triterpenoid saponins(1-16)featuring diverse structural variations in the side chain at C-17,along with twenty-one known analogues(17-37),have been isolated from the rhizomes of Gynostemma longipes ***,a plant renowned for its medicinal and edible *** structural elucidation of these compounds was accomplished through comprehensive analyses of 1D and 2D NMR and HRMS spectroscopic data,supplemented by comparison with previously reported *** assays on the isolates for their protective effects against hypoxia-induced damage in pheochromocytoma cells(PC12 cells)revealed that nine saponins exhibited significant anti-hypoxic *** investigation into the anti-hypoxia mechanisms of the representative saponins demonstrated that compounds 22 and 36 markedly reduced the levels of hypoxia-induced ***,these compounds were found to decrease the release of lactate dehydrogenase(LDH)and malondialdehyde(MDA),while increasing the activity of superoxide dismutase(SOD),thereby indicating that the saponins could mitigate hypoxia-induced injuries by ameliorating apoptosis and oxidative *** findings offer substantial evidence for the future utilization and development of ***,identifying dammarane-type triterpenoid saponins as its active anti-hypoxic constituents.

关键词： Gynostemma longipes Dammarane-type saponins Anti-hypoxia effect Apoptosis

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Human extracellular matrix(ECM)-like collagen and its bioactivity

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Regenerative Biomaterials 2024年第4期3卷 14-26页

作者： Hui Zhou Wenwei Li Lixin Pan Tianci Zhu Teng Zhou E.Xiao Qiang Wei State Key Laboratory of Polymer Materials and Engineering College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China Hunan Maybio Bio-pharmaceutical Co. LtdChangsha 410000China

Collagen,the most abundant structural protein in the human extracellular matrix(ECM),provides essential support for tissues and guides tissue *** its widespread use in tissue engineering,there remains uncertainty regarding the optimal selection of collagen ***-derived sources pose challenges such as immunogenicity,while the recombinant system is hindered by diminished *** this study,we hypothesized that human ECM-like collagen(hCol)could offer an alternative for tissue *** this study,a facile platform was provided for generating hCol derived from mesenchymal stem cells with a hierarchical structure and biochemical properties resembling native *** results further demonstrated that hCol could facilitate basal biological behaviors of human adipose-derived stem cells,including viability,proliferation,migration and adipocyte-like ***,it could promote cutaneous wound *** to its high similarity to native collagen and good bioactivity,hCol holds promise as a prospective candidate for in vitro and in vivo applications in tissue engineering.

关键词： extracellular matrix native-like collagen cell-derived matrix hierarchical structure

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High-throughput discovery of highly selective reversible hMAO-B inhibitors based on at-line nanofractionation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1772-1786页

作者： Yu Fan Jincai Wang Jingyi Jian Yalei Wen Jiahao Li Hao Tian Jacques Crommen Wei Bi Tingting Zhang Zhengjin Jiang Institute of pharmaceutical Analysis/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China/college of Pharmacy Jinan UniversityGuangzhou 510632China KU Leuven-University of Leuven Pharmaceutical AnalysisDepartment of Pharmaceutical and Pharmacological SciencesLeuven 3000Belgium Laboratory of Analytical pharmaceutical Chemistry Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium Department of Neurology the First Affiliated Hospital of Jinan University/Clinical Neuroscience Institutethe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

Human monoamine oxidase B(hMAO-B)has emerged as a pivotal therapeutic target for Parkinson's *** to adverse effects and shortage of commercial drugs,there is a need for novel,highly selective,and reversible hMAO-B inhibitors with good blood-brain barrier *** this study,a high-throughput at-line nanofractionation screening platform was established with extracts from Chuanxiong Rhizoma,which resulted in the discovery of 75 active compounds,including phenolic acids,volatile oils,and phthalides,two of which were highly selective novel natural phthalide hMAO-B inhibitors that were potent,selective,reversible and had good blood‒brain *** docking and molecular dynamics simulations elucidated the inhibition ***(IC_(50)=103 nmol/L;SI=645)and neocnidilide(IC_(50)=131 nmol/L;SI=207)demonstrated their excellent potential as hMAO-B *** offset the limitations of deactivating enzymes associated with irreversible hMAO-B inhibitors such as *** SH-SY5Y cell assays,sedanolide(EC_(50)=0.962μmol/L)and neocnidilide(EC_(50)=1.161μmol/L)exhibited significant neuroprotective effects,comparable to the positive drugs rasagiline(EC_(50)=0.896μmol/L)and safinamide(EC_(50)=1.079μmol/L).These findings underscore the potential of sedanolide as a novel natural hMAO-B inhibitor that warrants further development as a promising drug candidate.

关键词： Human monoamine oxidase B inhibitors High-throughput screening At-linenanofractionation Parkinson's disease Cellular neuroprotection Traditional Chinese medicines(TCMs)

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Protective effect of Zhizi Huangqi Shanzha formula(栀子黄芪山楂方) on aflatoxin poisoning in mice and its effect on intestinal flora

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Journal of Traditional Chinese Medicine 2024年第5期44卷 926-933页

作者： SUN Chuanbo XU Guangpei JIANG Ping HUANG Shipping CHEN Cunwu HE Yanfei college of Biotechnology and pharmaceutical Engineering West Anhui University

OBJECTIVE: To evaluate the protective effect of Zhizi Huangqi Shanzha formula(栀子黄芪山楂方, ZHSF) on aflatoxin-induced liver injury. METHODS: The protective effect of ZHSF on the aflatoxin-induced liver injury was evaluated by histological observation, blood cell analysis, evaluation of liver function and immunity, and gut microbiota analysis. RESULTS: ZHSF can significantly up-regulate the percentage of lymphocytes and eosinophils in the blood of Aflatoxin B1-intoxicated mice, down-regulate the levels of serum aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, and recover the liver tissue structure. Aflatoxin poisoning induces a variation of the intestinal flora of mice, and ZHSF may recover the variation of intestinal flora induced by Aflatoxin B1. Cluster analysis showed that the intestinal flora of mice in the intervention group was more similar to that of the control group. Correlation analysis showed that Lachnospiraceae, Desulfovibrio, and Lactobacillus may be the key flora for the pharmacological effects of ZHSF. CONCLUSIONS: ZHSF may protect against aflatoxininduced liver damage, improve immunity, and inhibit oxidative stress by regulating the composition and relative abundance of intestinal flora, which makes it a promising liver-protective candidate drug.

关键词： Zhizi Huangqi Shanzha formula aflatoxicosis gastrointestinal microbiome liver injury mice protective effect

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Veratrilla baillonii Franch alleviate the symptoms of diabetes in type 2 diabetic rats induced by high-fat diet and streptozotocin

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Food Science and Human Wellness 2024年第3期13卷 1378-1389页

作者： Chunlan Yan Zhihao Zhang Liqun Ma Xinyi Xu Muhammad Azhar Xianju Huang Jianxun Shi Jun Li college of Life Sciences South-Central Minzu UniversityWuhan 430074China college of pharmaceutical Science South-Central Minzu UniversityWuhan 430074China Department of Biosciences COMSATS University IslamabadSahiwal 57000Pakistan Zhejiang pharmaceutical University Ningbo 315100China Ethnopharmacology Level 3 Laboratory National Administration of Traditional Chinese MedicineSouth-Central Minzu UniversityWuhan 430074China

Our previous research studies have shown that Veratrilla baillonii Franch,a food supplement used by ethnic minorities in Southwest China,has multiple pharmacological activities,such as detoxification,antiinflammatory,antioxidant,and anti-insulin ***,the detailed signal pathways for its salutary effect on damages in multiple organs due to type 2 diabetes mellitus(T2DM)remains *** current study is to evaluate the therapeutic effects of *** on T2DM rats and to explore the underlying *** T2DM rat model was successfully established by a high-sugar and high-fat diet(HFD)combination with intraperitoneal injection of a small dose of streptozotocin(STZ,35 mg/kg).Biochemical analysis and histopatholgical examinations were conducted to evaluate the anti-diabetic potential of water extracts of ***(WVBF).The results showed that the WVBF treatment can improve hyperglycemia and insulin resistance,ameliorate the liver,kidney and pancreas injuries via decreasing inflammatory cytokines such as IL-6 and TNF-α,and oxidative *** investigation suggested that WVBF modulates the signal transductions of the IRS1/PI3K/AKT/GLUT4 and AMPK *** findings demonstrate potentials of WVBF in the treatment of T2DM and possible mechanisms for its hepatoprotective activities.

关键词： Veratrilla baillonii Franch Type 2 diabetes mellitus Liver injury Skeletal muscle GLUT4

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Silvestrol alleviates glioblastoma progression through ERK pathway modulation and MANBA and NRG-1 expression

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BIOCELL 2024年第7期48卷 1081-1093页

作者： LAN ZHOU QI ZHANG BO TIAN FENG YANG Neurosurgery Department The First Affiliated Hospital of Chongqing Medical and Pharmaceutical CollegeChongqingChina Neurosurgery Department Changdu People’s Hospital of TibetChangduChina

Background:Glioblastoma,a notably malignant tumor within the central nervous system,is distinguished by its aggressive ***,a robust inhibitor of the RNA helicase eukaryotic initiation factor 4A(eIF4A),has shown significant potential as an anticancer ***,the impact of silvestrol on glioblastoma,especially its molecular mechanisms,has not been fully ***:This investigation employed a variety of in vitro assays,such as cell counting kit-8(CCK-8),clonogenic,5-ethynyl-2′-deoxyuridine(EDU),wound healing,and flow cytometry,to evaluate cell cycle progression,apoptosis,cell viability,and *** blot analysis was also performed to study the apoptosis and extracellular regulated kinase(ERK)*** the ERK pathway was inhibited,differentially expressed genes(DEGs)in U87 cells were identified,followed by an analysis of target genes using the gene expression profiling interactive analysis(GEPIA)***:Silvestrol significantly suppressed the proliferation,migration,and colony formation of glioma *** caused cell cycle arrest and enhanced apoptosis in these ***,silvestrol stimulated the ERK pathway,with these effects being reversible by an ERK phosphorylation *** combined with GEPIA,GSCA,UALCAN,TIMER database screened 4 potential drug targets of silvestrol:chromosome 1 open reading frame 226(C1ORF226),mannosidase beta A(MANBA),IQ motif and Sec7 domain 2(IQSEC2),neuregulin 1(NRG-1).Among them,C1ORF226 was lower risk gene while MANBA,IQSEC2,and NRG-1 were high-risk ***,silvestrol notably reduced MANBA mRNA levels,which could be reversed by inhibiting ERK ***,silvestrol markedly decreased NRG-1 protein levels,with an additional reduction observed when the ERK pathway was ***:Silvestrol’s anti-glioma effects are primarily due to the suppression of MANBA expression via the ERK pathway and possibly by hindering the translation of N

关键词： Glioblastoma Silvestrol ERK pathway MANBA NRG-1

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