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Three rare anti-inflammatory sesquiterpene lactones from Magnolia grandiflora

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Chinese Journal of natural Medicines 2024年第3期22卷 265-272页

作者： XU Shuangyu ZHANG Feng TAO Linlan JIANG Yangming HUANG Tao LI Yanan HU Zhanxing YANG Jue HAO Xiaojiang YUAN Chunmao State Key Laboratory of Functions and Applications of medicinal plants Guizhou Medical UniversityGuiyang 550014China School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang 550025China natural products research center of Guizhou Province Guiyang 550014China State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China

Four new sesquiterpene lactones(SLs)(1–4),along with a biosynthetically related SL(5),have been isolated from the leaves of Magnolia *** A(1)is notable as the first C18 homogemarane type SL,featuring a unique 1,7-dioxaspiro[4.4]nonan-6-one *** 2 and 3,representing the first instances of chlorine-substituted gemarane-type SL analogs in natural products,were also *** structures of these isolates were elucidated through a combination of spectroscopic data analysis,electronic circular dichroism calculations,and X-ray single-crystal diffraction *** isolates demonstrated anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 ***,3–5 showed a significant inhibitory effect on nitric oxide production,with IC50 values ranging from 0.79 to 4.73μmol·L^(−1).Additionally,4 and 5 exhibited moderate cytotoxic activities against three cancer cell lines,with IC50 values between 3.09 and 11.23μmol·L^(−1).

关键词： Magnolia grandiflora Sesquiterpene lactones Isolation and identification Anti-inflammatory activity

Five quinolizidine alkaloids with anti-tobacco mosaic virus activities from two species of Sophora

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Chinese Chemical Letters 2024年第6期35卷 380-384页

作者： Ji Zhang Tong Zhang Qiao An Peng Zhang Cai-Yan Tian Chun-Mao Yuan Ping Yi Zhan-Xing Hu Xiao-Jiang Hao State Key Laboratory of Functions and Applications of medicinal plants Guizhou Medical UniversityGuiyang 550014China natural products research center of Guizhou Province Guiyang 550014China School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang 550025China School of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyang 550025China State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of ScienceKunming 650201China research Unit of Chemical Biology of natural Anti-Virus products Chinese Academy of Medical SciencesKunming 650201China

Three novel matrine-type alkaloids(1-3)and two unprecedented aloperine-type alkaloids(4 and 5)were isolated from the root of Sophora tonkinensis and the seeds of Sophora alopecuroides ***,compound 1 possessed an unprecedented 6/5/6 tricyclic skeleton,while compounds 2 and 3 characterized by rare 6/6/5/6 tetracyclic system and 6/6/6/6/6 pentacyclic system ***,compound 4 possessed an unprecedented 6/7/6/6 tetracyclic core,and compound 5 characterized by rare 6/6/6/6tetracyclic *** structures were elucidated by comprehensive spectroscopic data analysis and electronic circular dichroism(ECD)*** tests indicated that compound 5 displayed significant anti-tobacco mosaic virus(TMV)activity compared with the positive control ningnanmycin.

关键词： Matrine-type alkaloids Aloperine-type alkaloids Sophora tonkinensis Sophora alopecuroides Anti-tobacco mosaic virus

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

Constituents from leaves of Macaranga hemsleyana

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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 University Yunnan Key Laboratory of Pharmacology for natural products Haiyuan CollegeKunming Medical University

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 22known 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),benzyl β-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 Macaranga,The isolated compounds,11,14-16,and 20-22established taxonomic classification of *** in Euphorbiaceae *** were outstanding a

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

Josephin domain containing 2(JOSD2)promotes lung cancer by inhibiting LKB1(Liver kinase B1)activity

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Signal Transduction and Targeted Therapy 2024年第2期9卷 693-708页

作者： Tao Yuan Chenming Zeng Jiawei Liu Chenxi Zhao Fujing Ge Yuekang Li Meijia Qian Jiamin Du Weihua Wang Yonghao Li Yue Liu Xiaoyang Dai Jianya Zhou Xueqin Chen Shenglin Ma Hong Zhu Qiaojun He Bo Yang Institute of Pharmacology&Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 311199China Ministry of Education Key Laboratory of Chinese medicinal plants Resource from Lingnan Research Center of Medicinal Plants Resource Science and EngineeringGuangzhou University of Chinese MedicineGuangzhou 510006China center for Drug Safety Evaluation and research of Zhejiang University Hangzhou 310058China Department of Respiratory Disease Thoracic Disease CenterThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310006China Department of Oncology Hangzhou Cancer HospitalHangzhou 310002China Cancer center of Zhejiang University HangzhouChina Engineering research center of Innovative Anticancer Drugs Ministry of EducationHangzhouChina

Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths *** the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC ***,the need for novel strategies addressing NSCLC remains ***(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic ***,the mechanisms by which DUBs promote NSCLC remain poorly *** a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of *** of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in ***,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 ***,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in *** findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.

关键词： LKB1 inhibiting removing

Polyaspers A and B,the First Ergosterol-Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus ***507

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Chinese Journal of Chemistry 2024年第7期42卷 743-751页

作者： Hong Hu Lanqin Li Zhengyi Shi Xueqi Lan Yeting Zhang Xinye Huang Xincai Hao Qun Zhou Weiguang Sun Changxing Qi Yonghui Zhang Hubei Key Laboratory of natural medicinal Chemistry and Resource Evaluation Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Institute of Organ Transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Key Laboratory of Organ TransplantationMinistry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhanHubei 430030China Hubei Key Laboratory of Wudang Local Chinese Medicine research Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal PlantsCollege of PharmacyHubei University of MedicineShiyanHubei 442000China

Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this *** our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and B(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol B(4),were iso-lated from Aspergillus *** elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction *** A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder *** screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the EC50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control *** bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HaCaT *** an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic *** such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.

关键词： Psoriasis Aspergillus sp.TJ507 TNF-α Ergosterol-polyether adducts Inflammatory skin disease

Inhibiting the oligomerization of mycobacterial DNA-directed RNA polymerase(RNAP)using natural compound via in-silico techniques

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Medicine in Novel Technology and Devices 2024年第1期21卷 97-109页

作者： Ehssan H.Moglad Department of Pharmaceutics College of PharmacyPrince Sattam Bin Abdulaziz UniversityP.O.Box 173 Alkharj 11942Saudi Arabia Department of Microbiology and Parasitology Institute of Medicinal and Aromatic Plants ResearchThe National Center for ResearchP.O.Box 2404KhartoumSudan

Mycobacterium tuberculosis(Mtb)is responsible for the spread of tuberculosis(TB).The current study employed virtual screening of 2569 natural compounds against the DNA-directed RNA polymerase(RNAP)of Mtb to identify the possible binders that can inhibit its *** in-silico methodology included molecular docking to the compounds,further,the stability and flexibility of the best complexes were studied using molecular dynamics simulation,the MM/GBSA binding free energy technique with energy decomposition,PCA,FEL,steered MD simulation,and umbrella *** virtual screenings were conducted for the five RNAP subunits(chains A,B,C,D,and E)to identify a compound capable of inhibiting RNAP oligomerization.A promising compound,isoestradiol 3-benzoate,exhibited a low binding score(−7.28kcal/mol to−8.21kcal/mol)and showed binding ability with all subunits of the ***,the five complexes with isoestradiol 3-benzoate were selected for molecular dynamics simulation ***,RMSD showed that isoestradiol 3-benzoate bound with chain E showed the lowest RMSD of 0.49nm,while with chains A and B it had the most stable and consistent conformations with RMSD of 1.75nm and 1.2nm,*** H-bond between isoestradiol 3-benzoate and chains C and E showed the highest occupancy(58.27%,45.33%,and 50.80%,42.25%,11.75%).Moreover,the MMPBSA technique showed that isoestradiol 3-benzoate had a strong association with chains B and C(ΔGbind=−126.25±2.03 and−129.27±2.25).Additionally,free energy decomposition,PCA,FEL-steered MD simulation,and umbrella sampling were also performed to validate the association of the ligand with the *** 3-benzoate binds strongly to chains B and E;therefore,it should be considered as viable candidate for inhibiting the formation of RNAP protein complex,concluded in this study.

关键词： Mycobacterium tuberculosis DNA-Directed RNA polymerase Docking Steered MD simulation natural compounds Binding free energy Umbrella sampling

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan Qiyong Gong Zhongwei Gu Hao Cai Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of medicinal Chemistry for natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

Physiology of medicinal and aromatic plants under drought stress

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The Crop Journal 2024年第2期12卷 330-339页

作者： Zohreh Emami Bistgani Allen V.Barker Masoud Hashemi Isfahan Agricultural and natural Resources research and Education center Agricultural Research Education and Extension Organization(AREEO)Isfahan 81748-35117Iran Stockbridge School of Agriculture University of MassachusettsAmherstMA 01002USA

Drought poses a significant challenge,restricting the productivity of medicinal and aromatic *** strain induced by drought can impede vital processes like respiration and photosynthesis,affecting various aspects of plants’growth and *** response to this adversity,medicinal plants employ mechanisms such as morphological and structural adjustments,modulation of drought-resistant genes,and augmented synthesis of secondary metabolites and osmotic regulatory substances to alleviate the *** water scarcity can lead to leaf wilting and may ultimately result in plant *** cultivation and management of medicinal plants under stress conditions often differ from those of other *** is because the main goal with medicinal plants is not only to increase the yield of the above-ground parts but also to enhance the production of active ingredients such as essential *** elucidate these mechanisms of drought resistance in medicinal and aromatic plants,the current review provides a summary of recent literature encompassing studies on the morphology,physiology,and biochemistry of medicinal and aromatic plants under drought conditions.

关键词： Drought stress medicinal and aromatic plants Phytochemistry Physiology