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Acta Pharmaceutica Sinica B 2024年第7期14卷 3266-3280页

作者： Wenfeng Li Shuming Chen Jing Lang Jing Luo Jiahui Chen Liping Zhang Zhijie Sun Deli Dong department of Pharmacology China Pharmaceutical UniversityNanjing 210009China

The drugs extending healthspan in clinic have always been *** is an FDA-approved clinical antiprotozoal *** is rapidly metabolized to tizoxanide after absorption in *** previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and ***,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 ***,both nitazoxanide and tizoxanide improve high glucose-induced shortening of *** *** has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.

关键词： Nitazoxanide Tizoxanide C.elegans Healthspan Lifespan AMPK Akt Mitochondrial uncoupling

A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent Prunus species of southeast Asia

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Journal of Traditional Chinese Medicine 2024年第3期44卷 620-628页

作者： Shikha Agrawal Adarsh Kumar Ankit Kumar Singh Harshwardhan Singh Suresh Thareja Pradeep Kumar department of pharmaceutical Sciences and Natural Products Central University of Punjab

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian subcontinent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent,it extends from the Himalayas to Sikkim, Meghalaya,Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological,microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory,hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus species from its distribution, morphological characters to phytoconstituents, and pharmacological activity.

关键词： Prunus Rosaceae antineoplastic agents distribution hypoglycemic agents phytochemistry review

Pharmacological potential of Manilkara zapota(L.)***(Sapodilla):a narrative review

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Journal of Traditional Chinese Medicine 2024年第2期44卷 403-407页

作者： Priyanka Sharma Aakash Deep Harish Kumar Nitin Bansal Sanjiv Kumar Arun Davinder Kumar department of pharmaceutical Sciences Chaudhary Bansi Lal UniversityBhiwani 127021India department of pharmaceutical Sciences Maharishi Dayanand UniversityRohtak 124001India

Herbal medicine is safe and effective in treating various *** herbal medicine plays a tremendous role in treatment of various diseases and accompanying complications,hence herbal medicine requires remarkable attention in further research for the development of numerous active formulations for treatment of health *** plant needs special consideration for development and research of unidentified compound and characterization of novel active molecules that overcome multiple pathological *** genus Manilkara contains 135 plants around the *** overview discusses all the virtues of most important and commonly used plant Manilkara zapota(L.)***(***),also known as *** has various traditional beneficial effects in treatment of various diseases and disorders dating back to prehistoric times and used in ancient traditional system of herbal medicine.

关键词： herbal medicine Manilkara zapota phytoconstituents pharmacological activity review

Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization

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Nano Research 2024年第4期17卷 2908-2918页

作者： Guanting Li Fengli Xia Hongying Xiao Shunzhe Zheng Shuwen Fu Han Qiao Qianhui Jin Xuanbo Zhang Dun Zhou Chutong Tian Jin Sun Zhonggui He Bingjun Sun department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Emergency department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery ***,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous *** rational design of camptothecins-based prodrug nanoassemblies remains a ***,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug ***,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical *** length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and ***,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and *** findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based nanomedicines.

关键词： prodrug nanoassembly self-assembly antitumor efficacy tolerance 7-ethyl-10-hydroxycamptothecin(SN_(3)8)

Ethanol changes Nestin-promoter induced neural stem cells to disturb newborn dendritic spine remodeling in the hippocampus of mice

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Neural Regeneration Research 2024年第2期19卷 416-424页

作者： Guixiang Wang Wenjia Wang Ye Zhang Xiaoying Gou Qingqing Zhang Yanmiao Huang Kuo Zhang Haotian Zhang Jingyu Yang Yuting Li Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyangLiaoning ProvinceChina department of Pharmacology Shenyang Pharmaceutical UniversityShenyangLiaoning ProvinceChina

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system,particularly aberrant hippocampal *** this study,we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells(NSCs)and dendritic spine formation of newborn neurons in the subgranular zone of the dentate *** found abnormal orientation of tamoxifen-induced tdTomato+(tdTom^(+))NSCs in adult mice 2 months after treatment with EtOH(5.0 g/kg,i.p.)for 7 consecutive *** markedly inhibited tdTom^(+)NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to ***(100 mM)also significantly inhibited the proliferation to 39.2%and differentiation of primary NSCs in *** mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus,which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycinenhancer of zeste homolog 2 *** vivo tracing revealed that EtOH induced abnormal orientation of tdTom+NSCs and spatial misposition defects of newborn neurons,thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

关键词： adolescence adulthood ethanol dentate gyrus EZH2 in vivo tracing lineage progression mTOR neural stem cell newborn dendritic spine newborn neurons

Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

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Chinese Chemical Letters 2024年第2期35卷 323-328页

作者： Qiu Wang Qikun Jiang Dan Li Zimeng Yang Lin Gao Fan Liu Chang Li Yao Feng Zhonggui He Cong Luo Jin Sun department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Kangya of Ningxia pharmaceutical Co.Ltd. Yinchuan 750000China

Small interfering RNA(siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory ***,the effective delivery of siRNA to desired destination still remains challenging due to poor stability,high molecular weight and negative ***,ionizable lipid nanoparticle(LNP)has been extensively used as vector for effective delivery of ***,we report a mannose-modified LNP(M-MC_(3) LNP@TNFα)loading tumor necrosis factorα(TNFα)siRNA for targeting liver macrophages,achieving effectively inhibit acute liver *** M-MC_(3) LNP@TNFαnot only increases the internalization of LNP by macrophages,but also enhances the gene silencing efficiency of TNFαin ***,the M-MC_(3) LNP@TNFαexhibits higher accumulation in liver of healthy mice than that of MC_(3) LNP@TNFα(un-modified LNP)owing to the targeting effect of *** expected,the M-MC_(3) LNP@TNFαsignificantly suppresses the expression of TNFαand ameliorates liver damage in acute liver injury *** a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

关键词： Lipid nanoparticle Targeting siRNA delivery Acute liver injury Gene silencing Tumor necrosis factorα

Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

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Journal of Traditional Chinese Medicine 2024年第3期44卷 515-523页

作者： WANG Xiang HUANG Jianping WANG Yupeng WANG Qilong JING Yajiang ZHANG Gang PENG Liang GAO Jing WANG Hongyan YAN Yonggang department of Key Laboratory of "Qin pharmaceutical" Research and Development Shaanxi University of Traditional Chinese Medicine department of Yupeng Shaanxi Haitian pharmaceutical Co. Ltd. department of Acupuncture and Tuina Shaanxi University of Traditional Chinese Medicine

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

关键词： Dahuang () Taoren () differential metabolites kernel drug pairs metabolic networks and pathways metabolomics

Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics

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Journal of pharmaceutical Analysis 2024年第6期14卷 785-804页

作者： Patanachai K.Limpikirati Sorrayut Mongkoltipparat Thinnaphat Denchaipradit Nathathai Siwasophonpong Wudthipong Pornnopparat Parawan Ramanandana Phumrapee Pianpaktr Songsak Tongchusak Maoxin Tim Tian Trairak Pisitkun department of Food and pharmaceutical Chemistry Faculty of Pharmaceutical SciencesChulalongkorn UniversityPathumwanBangkok10330Thailand pharmaceutical Sciences and Technology(PST)Graduate Program Faculty of Pharmaceutical SciencesChulalongkorn UniversityPathumwanBangkok10330Thailand Center of Excellence in Systems Biology(CUSB) Faculty of MedicineChulalongkorn UniversityPathumwanBangkok10330Thailand department of pharmaceutical Chemistry Faculty of Pharmaceutical SciencesHuachiew Chalermprakiet UniversityBang PhliSamut Prakan10540Thailand Division of Research Affairs Faculty of MedicineChulalongkorn UniversityPathumwanBangkok10330Thailand

In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and *** specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered *** of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance *** attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the *** criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric *** in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial *** are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

关键词： Biopharmaceutical analysis Biopharmaceutical quality control Biopharmaceutical specifications Monoclonal antibodies Protein therapeutics Regulatory science

An efficient approach for the treatment of radioactive waste perfluoropolyether lubricants via a synergistic effect of thermal catalysis and immobilization

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Journal of Environmental Sciences 2024年第2期136卷 512-522页

作者： Xinhang Du Wenhua Tong Xinyu Zhou Jia Luo Yuqiu Liu Yabo Wang Panyu Li Yongkui Zhang department of pharmaceutical&Biological Engineering School of Chemical EngineeringSichuan UniversityChengdu 610065China

Perfluoropolyether(PFPE)lubricants are a kind of high-molecular polymer with many excellent ***,the use of PFPEs in the nuclear industry can lead to partial decomposition and carrying radionuclides,resulting in a large amount of radioactive waste PFPE lubricants ***,radioactive waste PFPE lubricants are difficult to be effectively treated due to their high stability,the risk of possible leakage of radionuclides,and hypertoxic fluorine-containing *** this study,without any precedent,a strategy of Mn O_(2)-catalyzed decomposition and Na_(2)CO_(3)-immobilized conversion was proposed for PFPE lubricant decomposition and fluorine immobilization simultaneously based on the Lewis acid-base and oxygen vacancies concept.A high fluorine conversion efficiency of 95.4%was ***,the mechanism of decomposition suggested that Mn O_(2)mainly provided Lewis acid sites and attacked the(basic)fluorine or oxygen atoms in PFPE *** decomposition of PFPE chains was proceed down and volatile fluorine-containing gas was released by partial electron transfer,intramolecular disproportionation reaction,and unzipping ***,gas by-products could be further oxidized and then immobilized into fluoride salts by carbonate solid ***,this study provides a simple,safe,and potentially practical strategy for the harmless conversion of refractory fluorinated organic wastes,especially perfluoropolymers.

关键词： Perfluoropolyether lubricants Catalyzed decomposition Fluorine-containing gas Immobilized conversion Fluoride

Reversibly size-switchable polyion complex micelles for antiangiogenic cancer therapy

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Chinese Chemical Letters 2024年第7期35卷 377-382页

作者： Mengjuan Sun Muye Zhou Yifang Xiao Hailei Tang Jinhua Chen Ruitao Zhang Chunjiayu Li Qi Ya Qian Chen Jiasheng Tu Qiyue Wang Chunmeng Sun NMPA Key Laboratory for Research and Evaluation of pharmaceutical Preparations and Excipients China Pharmaceutical UniversityNanjing 210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 211198China department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics China Pharmaceutical UniversityNanjing 210009China School of pharmaceutical Science Nanjing Tech UniversityNanjing 211816China

Size is one of the most important characteristics of nanoparticles to influence their biodistribution and antitumoral *** with large sizes have difficulty in deep tumor penetration,while small particles are easily removed from tumor tissues due to the high tumor interstitial fluid *** address these issues,an intelligent core-crosslinked polyion complex micelle(cPCM)with a reversibly sizeswitchable feature was engineered in this *** micelles are consisting of methoxy poly(ethylene glycol)-poly(D,L-lactide)copolymer(mPEG-PLA),mPEG-PLA-(HE)6CC,and mPEG-PLA-(RG)6CC at an optimal mass ratio of 6:1:1 with an antiangiogenic compound,dabigatran etexilate(DE),*** net charge inside the micelles is switchable when exposed to different pH conditions,thereby leading to revisable size-change of ***-loaded micelles(DE@cPCM)can swell and release drugs at the tumor sites with a mildly acidic pH,while they shrink and protect the cargo from leaking into the blood circulation with a neutral *** indicated that DE@cPCM can inhibit tumor angiogenesis in vitro and in vivo,thereby efficiently restraining tumor growth in a 4T1-bearing mouse ***,the sizeswitchable cPCM is a promising nanoplatform for targeting delivery of anticarcinogens into the matrix of tumor tissues.

关键词： Polyion complex micelle Size-switchable Revisable size-change pH response Antiangiogenic cancer