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Constituents from leaves of Macaranga hemsleyana

Chinese Herbal Medicines 2024年第3期16卷 481-486页

作者： Joseph Sakah Kaunda Jia Liu Yaojun Xu Yuansi Chen Chenfang Yue Xingjie Zhang Ruihan Zhang Muhammad Amin Weilie Xiao Hongliang Li Xiaoli Li Key laboratory of medicinal Chemistry for Natural Resource Ministry of EducationYunnan Characteristic Plant Extraction LaboratoryYunnan Provincial Center for Research&Development of Natural ProductsState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanSchool of PharmacySchool of MedicineChemical Science and TechnologyYunnan UniversityKunming 650500China Yunnan Key laboratory of pharmacology for Natural Products Haiyuan CollegeKunming Medical UniversityKunming 650500China

Objective:To study constituents of the leaves of Macaranga hemsleyana,and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activation,and antiproliferative ***:The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120,silica gel,Sephadex LH-20,and *** structures of compounds were determined by 1D,2D NMR,and HR-ESI-MS *** inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase(LDH)*** antiproliferative activity was evaluated using MTT ***:The study led to the isolation of 23 compounds,including one new compound,identified as(2Z)-3-[4-(β-D-glucopyranosyloxy)-2′-hydroxy-5′-methoxyphenyl]-2-propenoic acid(1),together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile(2),methyl 4-methoxynicotinate(3),4-methoxynicotinonitrile(4),1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone(5),neoisoastilbin(6),isoastilbin(7),aromadendrin(8),neoastilbin(9),astilbin(10),quercitrin(11),neoschaftoside(12),apigenin 6,8-bis-C-α-L-arabinoside(13),vitexin(14),bergenin(15),scopoletin(16),glucopyranoside salicyl(17),koaburside(18),benzylβ-D-glucoside(19),icariside B5(20),roseoside(21),loliolide(22),and adenosine(23).The tested compounds did not show LDH inhibition nor antiproliferative ***:Compound 1 was a new *** 2 and 3 were obtained for the first time from natural *** 22 known compounds constituted of alkaloids(2–4,23),phenolics(5,15,17,18),flavonoids(6–14),coumarin(16),benzyl glycoside(19),and norsesquiterpenes(20–22).All the compounds,1–23,were revealed from *** for the first *** is the initial uncovering of molecules 1–10,12,13,17–19,and 23 from the genus *** isolated compounds,11,14–16,and 20–22 established taxonomic classification of *** in Euphorbiaceae *** were outstanding as

关键词： antiproliferative activity chemotaxonomic significance flavonoids glycoside Macaranga hemsleyana Pax et Hoffm NLRP3 inflammasome

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Contemporary strategies and approaches for characterizing composition and enhancing biofilm penetration targeting bacterial extracellular polymeric substances

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Journal of Pharmaceutical Analysis 2024年第4期14卷 506-524页

作者： Lan Lu Yuting Zhao Mingxing Li Xiaobo Wang Jie Zhu Li Liao Jingya Wang Key laboratory of medicinal and Edible Plants Resources Development of Sichuan Education Department Sichuan Industrial Institute of AntibioticsSchool of PharmacyChengdu UniversityChengdu610000China Meishan Pharmaceutical Vocational College School of PharmacyMeishanSichuan620200China laboratory of Molecular pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhouSichuan646000China Hepatobiliary Surgery Langzhong People's HospitalLangzhongSichuan646000China

Extracellular polymeric substances(EPS)constitutes crucial elements within bacterial biofilms,facili-tating accelerated antimicrobial resistance and conferring defense against the host's immune *** precise and effective antibiofilm approaches and strategies,tailored to the specific charac-teristics of EPS composition,can offer valuable insights for the creation of novel antimicrobial ***,in turn,holds the potential to mitigate the alarming issue of bacterial drug *** analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias,which is likely due to the selection of a standard compound and the cross-interference of various EPS *** the pivotal role of EPS in biofilm functionality,it is imperative for EPS research to delve deeper into the analysis of intricate compositions,moving beyond the current focus on polymeric *** ne-cessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical *** this study,we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS ***,novel strategies aimed at targeting EPS to enhance biofilm penetration were explored,with a specific focus on high-lighting the limitations associated with colorimetric ***,we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these *** review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS,thereby inhibiting biofilm *** insight opens up a new avenue for exploration within this research domain.

关键词： Analytic strategies and approaches Composition characterization Extracellular polymeric substances(EPS) Promoting biofilm penetration

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Phomaketals A and B,pentacyclic meroterpenoids from a eupC overexpressed mutant strain of Phoma sp.

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Chinese Chemical Letters 2024年第7期35卷 350-354页

作者： Chuan Li Yangyang Han Yanan Zhai Ke Li Xingzhong Liu Zhuan Zhang Cai Jia Yongsheng Che NHC Key laboratory of biotechnology of Antibiotics Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key laboratory of Toxicology&Medical Countermeasures Beijing Institute of Pharmacology&ToxicologyBeijing 100850China Department of Microbiology College of Life SciencesNankai UniversityTianjin 300071China

Phomaketals A(1)and B(2),two tropolonic meroterpenoids with the unprecedented pentacyclic skeletons,were isolated from the solid-substrate fermentation cultures of a eupC overexpressed mutant strain of the fungus Phoma sp.,together with a biogenetically related secondary metabolite pughiinin B(3),and the known one noreupenifeldin B(4).The structures of 1–3 were elucidated primarily by nuclear magnetic resonance(NMR)*** absolute configurations of 1 and 2 were assigned by electronic circular dichroism calculations and the calculated NMR with DP4+analysis,while that of 3 was established by single-crystal X-ray diffraction analysis using Cu Kα***,phomaketals A(1)and B(2)could be derived from the hypothetical tropolonic sesquiterpene intermediates neosetophomone B(6)and 9-R-neosetophomone B(6),respectively,via different reactions *** 1 showed antiproliferative effect only against the SUPB15 cells,with an 50%inhibitory concentration(IC50)value of 4.85μmol/L,while the co-isolated known meroterpenoid 4 displayed potent effects against three tumor cell lines,SUPB15,EL4,and H9,showing IC50values of 0.36–27.08μmol/L.

关键词： Phoma sp. Tropolonic sesquiterpenes biosynthetic pathways Hetero-Diels–Alder Cytotoxicity

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The Multiple Roles of Autophagy in Neural Function and Diseases

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Neuroscience Bulletin 2024年第3期40卷 363-382页

作者： Yan-Yan Li Zheng-Hong Qin Rui Sheng Department of pharmacology and laboratory of Aging and Nervous Diseases Jiangsu Key laboratory of Neuropsychiatric DiseasesCollege of Pharmaceutical Sciences of Soochow UniversitySuzhou 215123China

Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes,where proteins,lipids,and organelles are degraded and *** to the way the cytoplasmic components are engulfed,autophagy can be divided into macroautophagy,microautophagy,and chaperone-mediated ***,many studies have found that autophagy plays an important role in neurological diseases,including Alzheimer's disease,Parkinson's disease,Huntington's disease,neuronal excitotoxicity,and cerebral *** maintains cell homeostasis in the nervous system via degradation of misfolded proteins,elimination of damaged organelles,and regulation of apoptosis and ***-mTOR,Beclin 1,TP53,endoplasmic reticulum stress,and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological ***,we discuss the role,functions,and signal pathways of autophagy in neurological diseases,which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies.

关键词： Autophagy Neurodegenerative diseases Cerebral ischemia AMPK mTOR Beclin 1 TP53 Endoplasmic reticulum stress

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An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

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Engineering 2024年第7期38卷 52-68页

作者： Xinyi Yang Congran Li Xiukun Wang Zhonghui Zheng Peiyi Sun Chunjie Xu Luni Chen Jiandong Jiang Staffan Normark Birgitta Henriques-Normark Xuefu You Beijing Key laboratory of Antimicrobial Agents/laboratory of pharmacology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Division for medicinal Microorganism-Related Strains CAMS Collection Center of Pathogenic MicroorganismsChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key laboratory of bioactive Substances and Functions of Natural Medicines Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Shandong Xinhua Pharmaceutical Co. Ltd.Zibo 255005China Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholm SE-17177Sweden State Key laboratory of bioactive Substances and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of medicinal biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Clinical Microbiology Karolinska University HospitalBioclinicumStockholm SE-17176Sweden

Antibacterial resistance is a global health threat that requires further concrete action on the part of all *** this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and *** several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in *** this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since *** was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other *** of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and *** them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in *** of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial ***,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in ***,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

关键词： Antimicrobial resistance New antibiotics Clinical pipelines WHO priority pathogens National Mega-Project for Innovative Drugs

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Isoimperatorin alleviates acetic acid-induced colitis in rats

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Asian Pacific Journal of Tropical biomedicine 2024年第4期14卷 147-153页

作者： Saied Goodarzi Amir Hossein Abdolghaffari Behnaz Najafi Mostafa Pirali Hamedani Saeed Tavakoli Mahshad Marvi Maryam Baeeri Narguess Yassa Abbas Hadjiakhoondi Mohammad Abdollahi Zahra Tofighi medicinal Plants Research Center Faculty of PharmacyTehran University of Medical SciencesTehranIran Department of Toxicology and pharmacology Faculty of PharmacyTehran Medical SciencesIslamic Azad UniversityTehranIran Department of Pharmacognosy Faculty of PharmacyTehran University of Medical SciencesTehranIran medicinal Plants Research Center Institute of Medicinal PlantsACECRKarajIran International Campus School of Pharmacy Tehran University of Medical SciencesTehranIran Toxicology and Diseases group The Pharmaceutical Sciences Research CenterTehran University of Medical SciencesTehranIran Department of Toxicology and pharmacology Faculty of PharmacyTehran University of Medical SciencesTehranIran

Objective:To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis ***:Colitis was induced by intracolonic administration of acetic acid solution(4%v/v)in *** were divided into six groups including the sham group,the negative control group,the dexamethasone-treated group,and the groups treated with isoimperatorin(0.1,1,and 10 mg/kg/d by gavage).The treatments were administered for three days and then colonic status was assessed by macroscopic,histopathological,and biochemical ***:Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced *** also significantly reduced myeloperoxidase,TNF-α,IL-1β,and malodialdehyde ***:Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

关键词： Isoimperatorin Inflammatory bowel disease Acetic acid Colitis TNF-α IL-1β

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Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway

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Chinese Journal of Integrative Medicine 2024年第11期30卷 1027-1034页

作者： GUO Fan HAN Xiao YOU Yue XU Shu-juan ZHANG Ye-hao CHEN Yuan-yuan XIN Gao-jie LIU Zi-xin REN Jun-guo CAO Ce LI Ling-mei FU Jian-hua Institute of Basic Medical Sciences of Xiyuan Hospital China Academy of Chinese Medical Sciences Beijing Key laboratory of Chinese Materia pharmacology Department of Central laboratory Kunshan Hospital of Chinese Medicine

Objective: To observe the protective effect and mechanism of hydroxyl safflower yellow A(HSYA)from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells(HUVECs). Methods:HUVECs were treated with oxygen-glucose deprivation reperfusion(OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations(1.25–160 μmol/L)of HSYA on HUVECs after OGD/R. HSYA 80 μmol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin(IL)-18, IL-1β, monocyte chemotactic protein 1(MCP-1), tumor necrosis factor α(TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3(NLRP3), gasdermin D(GSDMD) and GSDMD-N-terminal domain(GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt(CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1(Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. Results: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18,IL-1β, MCP-1, TNF-α and IL-6(P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3,Caspase-1, GSDMD and GSDMD-N proteins(P<0.01). Conclusions: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

关键词： Chinese medicine NLRP3 inflammasome human umbilical vein endothelial cells hydroxysafflor yellow A myocardial reperfusion injury oxygen-glucose deprivation reperfusion pyroptosis

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Ailanthone ameliorates pulmonary fibrosis by suppressing JUN-dependent MEOX1 activation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3543-3560页

作者： Lixin Zhao Yuguang Zhu Hua Tao Xiying Chen Feng Yin Yingyi Zhang Jianfeng Qin Yongyin Huang Bikun Cai Yonghao Lin Jiaxiang Wu Yu Zhang Lu Liang Ao Shen Xi-Yong Yu The Fifth Affiliated Hospital Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical PharmacologyNMPA&State Key LaboratorySchool of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China

Pulmonary fibrosis poses a significant health threat with very limited therapeutic options *** this study,we reported the enhanced expression of mesenchymal homobox 1(MEOX1)in pulmonary fibrosis patients,especially in their fibroblasts and endothelial cells,and confirmed MEOX1 as a central orchestrator in the activation of profibrotic *** high-throughput screening,we identified Ailanthone(AIL)from a natural compound library as the first small molecule capable of directly targeting and suppressing *** demonstrated the ability to inhibit both the activation of fibroblasts and endothelial-to-mesenchymal transition of endothelial cells when challenged by transforming growth factor-b1(TGF-b1).In an animal model of bleomycin-induced pulmonary fibrosis,AIL effectively mitigated the fibrotic process and restored respiratory ***,AIL acted as a suppressor of MEOX1 by disrupting the interaction between the transcription factor JUN and the promoter of MEOX1,thereby inhibiting MEOX1 expression and *** summary,our findings pinpointed MEOX1 as a cell-specific and clinically translatable target in ***,we demonstrated the potent anti-fibrotic effect of AIL in pulmonary fibrosis,specifically through the suppression of JUN-dependent MEOX1 activation.

关键词： Ailanthone MEOX1 Pulmonary fibrosis JUN TGF-b1 High-throughput screening Natural product

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Uncovering Chemical Interactions between Danshen and Danggui Using Liquid Chromatography–Mass Spectrometry and Network pharmacology-Based Research on Stroke

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 230-243页

作者： Han-Qing Pang Jia-Xiu Guo Xiao-Yu Shang Jian Wang Hui Liu Jing Tian Lu Zhang Jian-Bin Wang Wei Shi Bing-Chun Yan Liang Liu Department of Pharmacy School of MedicineInstitute of Translational MedicineYangzhou UniversityYangzhouChina School of Medicine Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile DiseasesYangzhou UniversityYangzhouChina School of Chemistry and Pharmaceutical Sciences State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources(Guangxi Normal University)GuilingChina Yangzhou Food and Drug Inspection and Testing Center YangzhouChina

Objective: The objective of this study was to decipher chemical interactions between Danshen and Danggui using liquid chromatography–mass spectrometry(LC-MS) and explore the mechanisms of Danshen–Danggui against stroke using network pharmacology and molecular docking. Materials and Methods: First, the chemical compounds of Danshen–Danggui were profiled using ultra-high-performance liquid chromatography(HPLC)-quadrupole time-of-flight MS. Accurately characterized compounds in various proportions of Danshen–Danggui were quantified using HPLC combined with triple quadrupole electrospray tandem MS. Network pharmacology was used to uncover the essential mechanisms of action of Danshen–Danggui against stroke. Discovery Studio Software was used for the molecular docking verification of key active chemicals and stroke-related targets. Results: A total of 53 compounds were characterized, and 22 accurately identified constituents(10 phenolic acids, 8 phthalides, and 4 tanshinones) were quantified in 15 proportions of Danshen–Danggui. The quantification results showed that Danggui significantly increased the dissolution of most phenolic acids(compounds from Danshen), whereas Danshen promoted the dissolution of most phthalides(compounds from Danggui). Overall, the combination of Danshen and Danggui at a 1:1 ratio resulted in the maximum total dissolution rate. Further network pharmacology and molecular docking results indicated that Danshen–Danggui exerted anti-stroke effects mainly by regulating inflammation-related(tumor necrosis factor, hypoxia-inducible factor, and toll-like receptor) signaling pathways, which ranked among the top three pathways based on Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Conclusion: The chemical compounds in Danshen–Danggui could interact with each other to increase the dissolution of the most active compounds, which could provide a solid basis for uncovering the compatibility mechanisms of Danshen–Danggui and Danshen–Danggu

关键词： Chemical interactions Danggui Danshen liquid chromatography–mass spectrometry network pharmacology

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Inhibition of tubulin detyrosination:a novel strategy to promote central nervous system regeneration

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Neural Regeneration Research 2024年第12期19卷 2557-2558页

作者： Charlotte Zeitler Marco Leibinger Dietmar Fischer Center of pharmacology Institute for PharmacologyMedical Faculty and University of CologneCologneGermany

The adult mammalian central nervous system(CNS) coordinates essential functions such as sensation,movement,autonomic control,thought processes,and ***,injuries or diseases of the CNS are often associated with devastating and permanent functional impairments because damaged axons normally fail to *** insufficient neuron-intrinsic growth capacity and an inhibitory environment at the injury site are the leading causes of this regenerative failure.

关键词： injuries sensation diseases

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