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Multiomics analyses of two Leonurus species illuminate leonurine biosynthesis and its evolution

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Molecular Plant 2024年第1期17卷 158-177页

作者： Peng Li Meng-Xiao Yan Pan Liu Dan-Jie Yang Ze-Kun He Yun Gao Yan Jiang Yu Kong Xin Zhong Sheng Wu Jun Yang Hong-Xia Wang Yan-Bo Huang Le Wang Xiao-Ya Chen Yong-Hong Hu Qing Zhao Ping Xu shanghai key laboratory of Plant Functional Genomics and Resources Shanghai Chenshan Botanical GardenShanghai Chenshan Plant Science Research CenterChineseAcademy of SciencesShanghaiChina College of Life Sciences Shanghai Normal UniversityShanghai 200234China State key laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghaiChina University of the chinese Academy of Sciences Beijing 100049China The research Center of Chiral Drugs Innovation Research Institute of Traditional Chinese MedicineShanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai 201203China College of Chemistry and chemical Engineering Shanghai University of Engineering ScienceShanghai 201620China

The Lamiaceae family is renowned for its terpenoid-based medicinal components,but Leonurus,which has traditional medicinal uses,stands out for its alkaloid-rich ***,the principal active compound found in Leonurus,has demonstrated promising effects in reducing blood lipids and treating ***,the biosynthetic pathway of leonurine remains largely ***,we present the chromosome-level genome sequence assemblies of Leonurus japonicus,known for its high leonurine production,and Leonurus sibiricus,characterized by very limited leonurine *** integrating genomics,RNA sequencing,metabolomics,and enzyme activity assay data,we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase(ADC),uridine diphosphate glucosyltransferase(UGT),and serine carboxypeptidase-like(SCPL)acyltransferase enzymes that catalyze key reactions in this *** analyses revealed that the UGT–SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in ***,which contributed to the accumulation of leonurine specifically in ***,our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.

关键词： Lamiaceae Leonurus japonicus Leonurus sibiricus genome sequence alkaloids leonurine gene cluster biosynthetic pathway evolution

Exosome-biomimetic nanocarriers for oral drug delivery

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chinese chemical Letters 2024年第9期35卷 65-71页

作者： Fengjie Liu Fansu Meng Zhenjiang Yang Huan Wang Yuehong Ren Yu Cai Xingwang Zhang Department of Pharmaceutics College of PharmacyJinan UniversityGuangzhou 511443China Zhongshan Hospital of traditional chinese medicine Affiliated to Guangzhou University of TCM Zhongshan 528400China Shenzhen traditional chinese medicine Hospital Shenzhen 518033China State key laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhou 511443China

Exosomes as authigenous nanovesicles secreted by living cells represent a significant class of *** virtue of their unique roles in intercellular communication,exosomes can mediate intercellular information/cargoes exchange as messenger and facilitate drug delivery as smart *** medication is the most clinically relied upon route of administration and can achieve both topical and systemic therapeutic effects after *** and exosome-derived vectors have shown to be of high value in oral drug delivery,since they enable efficient oral delivery of therapeutic molecules by targeting intestinal epithelial *** recent years,exosome-biomimetic nanocarriers have emerged as an important catalyzer in innovating oral drug delivery *** this work,we roundly reviewed the biogenesis and functions of exosomes,their extraction and characterization methods,resources available for exosomes harvest,and design philosophy of exosome-derived vehicles,particularly highlighting the oral delivery application of exosome-biomimetic nanocarriers for diverse *** evidence suggests that exosome-biomimetic nanocarriers hold great promise for oral delivery of intractable drugs with potential biopharmaceutic issues.

关键词： Exosomes Oral delivery Biomimetic nanocarriers Targeting Bioavailability

Composition analysis of Compound Shenhua Tablet,a seven-herb chinese medicine for IgA nephropathy:evaluation of analyte-capacity of the assays

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chinese Journal of Natural medicines 2024年第2期22卷 178-192页

作者： ZHANG Haiyan WANG Qiuyue WANG Jianan ZHANG Sichao JIA Weiwei HE Ning XIA Xiaoyan WANG Ting LAI Liyu LI Jiaying DU Jing OLALEYE Olajide E CHEN Xiangmei YANG Junling LI Chuan Graduate School Tianjin University of Traditional Chinese MedicineTianjin 301617China State key laboratory of Drug research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy University of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100049China Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People’s Liberation ArmyNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China Zhongshan Institute for Drug Discovery Zhongshan 528400China Haihe laboratory of Modern chinese medicine Tianjin 301617China

Compound Shenhua Tablet,a medicine comprising seven herbs,is employed in treating IgA *** study aimed to meticulously analyze its chemical *** on a list of candidate compounds,identified through extensive literature review pertinent to the tablet’s herbal components,the composition analysis entailed the systematic identification,characterization,and quantification of the *** analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was *** identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents’daily doses.A total of 283 constituents,classified into 12 distinct categories,were identified and characterized in the Compound Shenhua *** constituents exhibited content levels of 1−10982μg·g^(−1),with daily doses of 0.01−395μmol·d^(−1).The predominant constituents,with daily doses of≥10μmol·d^(−1),include nine organic acids(citric acid,quinic acid,chlorogenic acid,cryptochlorogenic acid,gallic acid,neochlorogenic acid,isochlorogenic acid C,isochlorogenic acid B,and linoleic acid),five iridoids(specnuezhenide,nuezhenoside G13,nuezhenidic acid,secoxyloganin,and secologanoside),two monoterpene glycosides(paeoniflorin and albiflorin),a sesquiterpenoid(curzerenone),a triterpenoid(oleanolic acid),and a phenylethanoid(salidroside).Additionally,there were 83,126,and 55 constituents detected in the medicine with daily doses of 1–10,0.1–1,and 0.01–0.1μmol·d^(−1),*** combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the *** comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.

关键词： Compound Shenhua Tablet Composition analysis Analyte-capacity

The chromosome-scale assembly of the Notopterygium incisum genome provides insight into the structural diversity of coumarins

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3760-3773页

作者： Qien Li Yiqun Dai Xin-Cheng Huang Lanlan Sun Kaixuan Wang Xiao Guo Dingqiao Xu Digao Wan Latai An Zixuan Wang Huanying Tang Qi Qi Huihui Zeng Minjian Qin Jia-Yu Xue Yucheng Zhao Tibetan medicine research Center of Qinghai University Tibetan Medical CollegeQinghai UniversityXining 810016China School of Pharmacy Bengbu Medical UniversityBengbu 233030China Department of Resources Science of traditional chinese medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China College of Horticulture Bioinformatics CenterAcademy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjing 210095China key laboratory of Shaanxi Administration of traditional chinese medicine for TCM Compatibility Shaanxi University of Chinese MedicineXi’an 712046China

Coumarins,derived from the phenylpropanoid pathway,represent one of the primary metabolites found in *** alignment of the tetrahydropyran(THP)and tetrahydrofuran(THF)rings with the lactone structure results in the formation of at least four types of complex ***,the mechanisms underlying the structural diversity of coumarin remain poorly ***,we report the chromosome-level genome assembly of Notopterygium incisum,spanning 1.64 Gb,with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding ***,we identified the key enzymes responsible for shaping the structural diversity of coumarins,including two p-coumaroyl CoA 2′-hydroxylases crucial for simple coumarins basic skeleton architecture,two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis,and five CYP736 cyclases involved in THP and THF ring ***,two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first *** analysis implies that tandem and ectopic duplications of the CYP736 subfamily,specifically arising in the Apiaceae,contributed to the structural diversity of coumarins in ***,this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

关键词： Notopterygium incisum Parallel evolution Biosynthesis Pyranocoumarins Furanocoumarins

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

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traditional medicine research 2024年第2期9卷 42-51页

作者： Shu-Man Liu Zi-Jie Yan Man Xiao Yi-Qiang Xie College of traditional chinese medicine Hainan Medical UniversityHaikou 571199China key laboratory of Biochemistry and Molecular biology Hainan Medical UniversityHaikou 571199China.

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against ***:We screened effective compounds and drug targets using chinese medicine systemic pharmacology database and analysis platform and chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene *** potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease *** software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key *** vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western ***:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were *** constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of *** vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expressi

关键词： Gualou Qumai pill diabetic kidney disease disorder of lipid metabolism network pharmacology molecular docking

Seco-cyclic phorbol derivatives and their anti-HIV-1 activities

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chinese Journal of Natural medicines 2024年第4期22卷 365-374页

作者： HUANG Xiaolei HUANG Xusheng LI Qirun MA Mengdi CUI Yadong YANG Liumeng WANG Haibo LUO Ronghua CHEN Jinglei YANG Jingxuan LIN Jinrong LI Duxin ZHENG Yongtang ZHANG Jian College of Pharmaceutical Science Soochow UniversitySuzhou 215123China key laboratory of Animal Models and Human Disease Mechanisms of the chinese Academy of Sciences/key laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming 650204China College of traditional chinese medicine Yunnan University of Chinese MedicineKunming 650500China

Phorbol esters are recognized for their dual role as anti-HIV-1 agents and as activators of protein kinase C(PKC).The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20,C3/C4,and C9 of ***,the lipids located at positions C12/C13 are essential for both the anti-HIV-1 activity and the formation of the PKC-ligand *** influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti-HIV-1 activity requires further *** research entailed the hydrolysis of phorbol,producing seco-cyclic phorbol *** anti-HIV-1 efficacy of these derivatives was assessed,and the affinity constant(Kd)for PKC-δprotein of selected seco-cyclic phorbol derivatives was determined through isothermal titration *** findings suggest that the chemical modification of cyclopropanols could affect both the anti-HIV-1 activity and the PKC binding ***,compound S11,with an EC_(50) of 0.27μmol·L^(−1) and a CC_(50) of 153.92μmol·L^(−1),demonstrated a potent inhibitory effect on the intermediate products of HIV-1 reverse transcription(ssDNA and 2LTR),likely acting at the viral entry stage,yet showed no affinity for the PKC-δ*** results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti-HIV-1 activity.

关键词： seco-Cyclic phorbol derivatives Hydrolysis reaction Cyclopropane ring Esterification Anti-HIV-1 agent

Human pangenome:far-reaching implications in precision medicine

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Frontiers of medicine 2024年第2期18卷 403-409页

作者： Yingyan Yu Hongzhuan Chen Department of General Surgery of Ruijin Hospital Shanghai Institute of Digestive Surgeryand Shanghai Key Laboratory for Gastric NeoplasmsShanghai Jiao Tong University School of MedicineShanghai200025China Shuguang Lab for Future Health Shanghai Frontier Science Center of TCM Chemical BiologyShanghai University of Traditional Chinese MedicineShanghai201203China

*** May 11,2023,the internationally renowned journal Nature announced that a first draft of the human pangenome reference has been constructed[1].This research was carried out by the Human Pangenome Reference Consortium(HPRC).One month later,on June 14,2023,a pangenome reference of 36 chinese populations was published on journal Nature[2],which was performed by chinese Pangenome Consortium(CPC).As the scientists pointed out that since the Human Genome Project(HGP)published the human reference genome,it provided a reference blueprint for genomic ***,the limitations of the human reference genome have gradually emerged,and it is difficult to reflect the genome diversity of the"human"species.

关键词： Human journal limitations

New strategies for asymmetric photocatalysis: asymmetric organocatalytic/photoredox relay catalysis for efficient synthesis of polycyclic compounds containing vicinal amino alcohols

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Science China Chemistry 2024年第3期67卷 945-952页

作者： Jia-Lu Zhang Wen-Bo He Xiu-Qin Hu Peng-Fei Xu State key laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou UniversityLanzhou 730000China State key laboratory of Veterinary Etiological biology College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730000China MOE Frontiers Science Center for Rare Isotopes Lanzhou UniversityLanzhou 730000China

An asymmetric catalytic strategy in photocatalysis utilizing a chirality-induced approach through an organocatalytic/photoredox relay catalysis strategy is successfully achieved for the rapid construction of polycyclic compounds containing vicinal amino alcohols in a one-pot protocol. This methodology facilitates the efficient synthesis of diverse substituted polycyclic tetrahydroquinoline and benzofuran-derived vicinal amino alcohols, each containing five consecutive chiral centers, with high yields,excellent diastereoselectivities and enantioselectivities(up to 95% yield, >20:1 dr and 98% ee), under mild reaction conditions driven by sequential bifunctional squaramide organocatalyst-catalyzed [4+2] annulation and photocatalyst-catalyzed ketyl radical addition cyclization reaction process. Furthermore, investigations into the stereoselectivity mechanism and high-resolution mass spectrometry(HRMS) experiments on free radical trapping have provided evidence for elucidating the detailed mechanism of chirality-induced processes and chiral intermediate conversions in this procedure.

关键词： enantioselective photocatalysis asymmetric organocatalytic/photocatalysis relay catalysis five consecutive chiral centers chirality-induced strategy chirality vicinal amino alcohols

Let-7i-5p maintains the stemness via R-spondin2/Wnt pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 20-23页

作者： Qinghua Wei Xueshan Dai Jiahui Wei Wenwei Sun Xiaoqian Yang Yuxin Zhang Xin Guo Yi Chen College of Pharmaceutical Sciences&chinese medicine Southwest UniversityChongqing 400716China Center for Basic Medical research TEDA International Cardiovascular HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300457China Chongqing key laboratory of New Drug Screening from traditional chinese medicine Chongqing 400716China pharmacology of chinese Materia Medica-the key Discipline Constructed by the State Administration of traditional chinese medicine Chongqing 400716China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510006China National Demonstration Center for Experimental Pharmacy Education(Southwest University) Chongqing 400716China Engineering research Center of Coptis Development and Utilization(Ministry of Education) College of Pharmaceutical Sciences and Chinese MedicineSouthwest UniversityChongqing 400716China

Cancer stem cells(CSCs)are related to tumorigenesis,recurrence,metastasis,and drug resistance in hepatocellular carcinoma(HCC).1 Let-7i is a noncoding small RNA,belonging to the famous miRNA let-7 ***,let-7i has been ... 详细信息

关键词： hepatocellular Cancer metastasis