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Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第01期 288-296页

作者： Shuai Liu Wen-Qiang Xu Ying-Tong Di Man-Cheng Tang Ding-Kang Chen Ming-Ming Cao Yao-Wen Chang Hong-Yu Tang Chun-Mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo Zi-Fei Xu Ying Zeng Yun-Dong Wu Xiao-Jiang Hao key laboratory of Phytochemistry and natural medicines (Chinese Academy of Sciences) Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Lab of Computational Chemistry and drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay laboratory state key laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University state key laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan key laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

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Identification of a dual functional betulinic acid analog for the treatment of osteoarthritis by phenotypic screening

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Science China Life Sciences 2025年第1期 300-302页

作者： Ze-Min Lin Mai Xiang Wen-Hui Wei Shu-Hui Fan Li Chen Jie Wang Xiao-Qian Yang Chun-Hao Yang Shi-Jun He Jian-Ping Zuo laboratory of Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy University of Chinese Academy of Sciences School of Pharmacy Nanjing University of Chinese Medicine state key laboratory of drug Research Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of Sciences Innovation Research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Experiment center for Science and Technology Shanghai University of Traditional Chinese Medicine

Dear Editor, Phenotypic drug discovery, which observes compound effects on physiology,has given way to targeting specific molecules, but has revived by using modern methods to find drugs based on therapeutic outcomes in disease models(Vincent et al., 2022). Osteoarthritis(OA) is a prevalent chronic joint disorder, primarily affecting knee joints, with osteoclast activation due to low-grade inflammation resulting in increased bone resorption and structural changes in the joint(Katz et al.,2021).

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New flavonoids and methylchromone isolated from the aerial parts of Baeckea frutescens and their inhibitory activities against cyclooxygenases-1 and -2

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Chinese Journal of natural medicines 2018年第8期16卷 615-620页

作者： ZHOU Jun-Neng YAN Ming GAO Peng HOU Ji-Qin PHAM Thi-Anh WANG Hao state key laboratory of natural medicines Department of Natural Medicinal ChemistryChina Pharmaceutical University Jiangsu key laboratory of drug screening China Pharmaceutical University

In the present study,we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens,which resulted in the isolation of two new flavonoid glycosides,myricetin 3-O-(5'-O-galloyl)-α-L-arabinofuranoside(1),6-methylquercetin 7-O-β-D-glucopyranoside(2),one new methylchromone glycoside,7-O-(4',6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone(3),together with three known compounds(4-6).The structures of these isolated compounds were established on the basis of 1 D and 2 D NMR techniques and chemical *** anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and-2 in *** 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC50 values ranging from 1.95 to 5.54 μmol·L^(-1) and ranging from 1.01 to 2.27 μmol·L^(-1),respectively.

关键词： Baeckea frutescens Flavonoid Methylchromone Cyclooxygenase-1 Cyclooxygenase-2

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Fast-onset antidepressant targeting the nNOS-SERT interaction in the DRN

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Chinese Journal of natural medicines 2023年第1期21卷 1-2页

作者： GUAN Xin PANG Tao state key laboratory of natural medicines New Drug Screening CenterChina Pharmaceutical UniversityNanjing 210009China

Major depressive disorder is one of the most deleterious mental disorders with a high suicide rate,incidence and recurrence rate,which is manifested as continuous depression,retardation of thinking as well as loss of ... 详细信息

关键词： Depression nNOS SERT Antidepressant Fast-onset

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Commentary:brain endothelial GSDMD as a novel target for brain disorders associated with BBB damage

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Chinese Journal of natural medicines 2024年第7期22卷 580-581页

作者： LIU Kui PANG Tao state key laboratory of natural medicines New Drug Screening and Pharmacodynamics Evaluation CenterChina Pharmaceutical UniversityNanjing 210009China

The blood-brain barrier(BBB)is a highly selective and critical interface between the blood and the central nervous system(CNS),essential for maintaining the microenvironment necessary for normal brain function and homeostasis[1].The BBB is primarily formed by brain endothelial cells(bECs),pericytes,and astrocytes,and it operates in concert with microglia/macrophages and neurons[2,3]to constitute the neurovascular unit(Fig.1).Disruption of the BBB or the presence of systemic inflammation can precipitate or exacerbate various CNS pathologies,including Alzheimer’s disease[4],amyotrophic lateral sclerosis[5],Huntington’s disease[6]and multiple sclerosis.

关键词： Brain endothelial cells GSDMD Blood-brain barrier natural products Neuroinflammation Brain disorders

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Nitric oxide donating anti-glaucoma drugs:advances and prospects

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Chinese Journal of natural medicines 2020年第4期18卷 275-283页

作者： MAO Yu-Jie WU Jian-Bing YANG Ze-Qiu ZHANG Yi-Hua HUANG Zhang-Jian state key laboratory of natural medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Drug DiscoveryChina Pharmaceutical UniversityNanjing 210009China

Glaucoma is a disease that causes irreversible blindness. Reducing intraocular pressure(IOP) is the main treatment at present. Nitric oxide(NO), an endogenous gas signaling molecule, can increase aqueous humor outflow facility, inhibit aqueous humor production thereby reducing IOP, as well as regulate eye blood flow and protect the optic nerve. Therefore, NO donating antiglaucoma drugs have broad research prospects. In this review, we summarize NO-mediated therapy for glaucoma, and the state of the art of some NO donating molecules, including latanoprostene bunod in market and some other candidate compounds, for the intervention of glaucoma, as well as prospects and challenges ahead in this field.

关键词： Nitric oxide Glaucoma Intraocular pressure Trabecular meshwork Prostaglandin analogues

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Design, synthesis, and biological evaluation of ligustrazine/resveratrol hybrids as potential anti-ischemic stroke agents

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Chinese Journal of natural medicines 2020年第8期18卷 633-640页

作者： ZHANG Yin-Qiu WU Jian-Bing YIN Wei ZHANG Yi-Hua HUANG Zhang-Jian state key laboratory of natural medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Drug DiscoveryChina Pharmaceutical UniversityNanjing 210009China

To search for potent anti-ischemic stroke agents,a series of tetramethylpyrazine(TMP)/resveratrol(RES)hybrids 6 a-t were designed and *** hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,6 d,6 g-i,6 o and 6 q were more active than *** most active compound 6 h exhibited more potent antiplatelet aggregation activity than TMP,RES,as well as positive control ticlopidine(Ticlid)and aspirin(ASP).Furthermore,6 h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide(H2 O2)or hydroxyl radical(·OH).Importantly,6 h significantly protected primary neuronal cells suffered from oxygen-glucose deprivation/reoxygenation(OGD/R)injury,comparable to an anti-ischemic drug edaravone(Eda).Together,our findings suggest that 6 h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.

关键词： Ligustrazine Resveratrol Hybrids Anti-platelet aggregation Antioxidant Ischemic stroke

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Collaborative assembly-mediated siRNA delivery for relieving inflammation-induced insulin resistance

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Nano Research 2020年第11期13卷 2958-2966页

作者： Shiyang Shen Li Zhang Mengru Li Zhizi Feng Huixia Li Xiao Xu Shiqi Lin Ping Li Can Zhang Xiaojun Xu Ran Mo state key laboratory of natural medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Advanced Pharmaceuticals and BiomaterialsChina Pharmaceutical UniversityNanjing210009China

Obesity plays a primary causative role in insulin resistance and hyperglycemia that contributes to type 2 *** lipid storage in the liver renders activation of the resident macrophages and chronic secretion of inflammatory mediators,therefore causing or aggravating insulin ***,we develop collaborative assemblies using a“one-pot”synthesis method for macrophage-specific delivery of small interfering RNAs(siRNAs)that target the inflammatory *** nanocomplex(NC)composed of the siRNA molecule,a synthetic thiol-bearing methacrylated hyaluronic acid(sm-HA)and protamine forms through an electrostatic-driven physical assembly,which is chemically crosslinked to acquire the collaboratively assembled nanocapsule(cNC)*** obtained cNC displays significantly higher stability than *** moieties as flexible assembly units can be easily equipped on cNC for long circulation,active targeting,or controlled siRNA ***-F decorated with folic acid,a macrophage-targeting ligand promotes the siRNA accumulation in the activated macrophages in the liver of the obese mouse ***-F loaded with siRNA targeting inflammatory indicators efficiently control the macrophage inflammatory response by reducing the expression of the inflammatory proteins(>40%reduction)and ameliorating the insulin resistance symptoms of the obese mice.

关键词： small interfering RNA(siRNA)delivery collaborative assembly nanomedicine insulin resistance diabetes

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Cell-based drug delivery systems for biomedical applications

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Nano Research 2018年第10期11卷 5240-5257页

作者： Teng Li He Dong Can Zhang Ran Mo state key laboratory of natural medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of AdvancedPharmaceuticals and 8iomaterials China Pharmaceutical University Nanjing 210009 China

Spurred by numerous achievements in nanoscience and nanotechnology, the evolution of nanoparticulate drug delivery systems （nano-DDSs） is in its rapid growth period and attracting considerable attention due to their unique advantages in biomedical applications. natural particulates ranging from mammalian cells to bacteria possess their own distinctive delivery processes and mechanisms, which inspires more design and development of cell-based DDSs by integrating the innate functions of cells with the nanoscale characteristics of nanoparticles. In this review article, we focus on the recent advances in cell-based DDSs for site-specific delivery of therapeutics and enhanced treatment of diseases. The promise and perils of cell-based DDSs are also discussed.

关键词： natural particulates nanotechnology bioinspired drug delivery biomedical application

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Ultra-warm artificial aerogel fibers:a biomimetic material based on polar bear hair

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Chinese Journal of natural medicines 2024年第6期22卷 481-482页

作者： LI Yu LI Siwen state key laboratory of natural medicines Jiangsu Key Laboratory of Drug ScreeningDepartment of Biomedical EngineeringSchool of EngineeringChina Pharmaceutical UniversityNanjing 211198China

Aerogels are widely recognized as the premier thermal insulation materials due to their high porosity and exception-ally low thermal conductivity^([1,2]).Regrettably,their wide-spread application in thermal insulation textiles is signific-antly limited by their fragility and poor ***-though many aerogel fibers made with silica^([3]),graphene^([4,5]),carbon nanotube^([6]),titanium oxide^([7]),and cellulose^([8])have been prepared through various methods.

关键词： Aerogel fibers Biomimetic materials Green technologies

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