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natural products

World Journal of Traditional Chinese Medicine 2017年第2期 53-53页

THE WONDER OF THE natural WORLD.THE POWER OF natural products.GO SEAMLESSLY.From biomarker and drug discovery to safety,quality control and manufacturing efficiency,Waters is equipped and committed to help labs navigate the wonderful complexity of natural products.Together as industry pioneers,let’s embrace the challenges and pursue new possibilities that are waiting to be uncovered.

关键词： EN natural products

Potential protective effects of the water-soluble Chinese propolis on experimental ulcerative colitis

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中医杂志:英文版 2023年第5期43卷 925-933页

作者： ZHOU Hua LI Hui WANG Haihua Department of Physiology Anhui Medical CollegeHefei 230601China Department of Physiology Wannan Medical CollegeWuhu 241002China

OBJECTIVE: To investigate the outcome of Chinese water-soluble propolis(WSP) on the inflammatory response and oxidative stress(OS) of colonic mucosa in rats with ulcerative colitis. METHODS: Dextran sulfate sodium(DSS) was employed to establish the ucerative colitis(UC) rat model. Fortyeight male rats were arbitrarily separated into six groups, namely control, UC, low-dose water-soluble propolis(LWSP), medium-dose water-soluble propolis(M-WSP), high-dose water-soluble propolis(H-WSP), and sulfasalazine(Sulfa). In this study, we adopted a method of pre-administration and reconstruction of the model that assessed the water-soluble propolis mediated protection against DSS-induced UC rats. Moreover, we examined the body weight(BW), disease activity index(DAI), bloody stool, colon length, and intestinal mucosal injury index of rats. In addition, using enzyme linked immunosorbent assays, we assessed indicators, such as, colonic myeloperoxidase(MPO), interleukin-6(IL-6), interleukin-9(IL-9), tumor necrosis factor-ɑ(TNF-ɑ), superoxide dismutase(SOD), malondialdehyde, and glutathione peroxidase(GSH-Px) levels. RESULTS: The pro-inflammatory cytokine expression, as well as OS, was increased in the model rats. However, upon WSP intervention, both pro-inflammatory cytokine levels and OS reduced dramatically, and the therapeutic effect was dose-dependent. CONCLUSION: WSP downregulates OS by enhancing the function of endogenous antioxidant enzymes like SOD and GSH-Px, that inhibit neutrophil activity, as well as diminish pro-inflammatory cytokines like TNF-ɑ, IL-6, and IL-9, along with mechanisms that attenuate intestinal inflammation in UC rat model.

关键词： ulcerative colitis natural products oxidative stress water-soluble propolis pro-inflammatory cytokine

natural product-based radiopharmaceuticals:Focus on curcumin and its analogs,flavonoids,and marine peptides

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Journal of Pharmaceutical Analysis 2022年第3期12卷 380-393页

作者： Hendris Wongso Labeled Compound and Radiometry Division Center for Applied Nuclear Science and TechnologyNational Nuclear Energy AgencyBandung40132Indonesia

natural products provide a bountiful supply of pharmacologically relevant precursors for the development of various drug-related molecules,including radiopharmaceuticals.However,current knowledge regarding the importance of natural products in developing new radiopharmaceuticals remains limited.To date,several radionuclides,including gallium-68,technetium-99m,fluorine-18,iodine-131,and iodine-125,have been extensively studied for the synthesis of diagnostic and therapeutic radiopharmaceuticals.The availability of various radiolabeling methods allows the incorporation of these radionuclides into bioactive molecules in a practical and efficient manner.Of the radiolabeling methods,direct radioiodination,radiometal complexation,and halogenation are generally suitable for natural products owing to their simplicity and robustness.This review highlights the pharmacological benefits of curcumin and its analogs,flavonoids,and marine peptides in treating human pathologies and provides a perspective on the potential use of these bioactive compounds as molecular templates for the design and development of new radiopharmaceuticals.Additionally,this review provides insights into the current strategies for labeling natural products with various radionuclides using either direct or indirect methods.

关键词： natural products Radiopharmaceuticals Radiolabeling Curcumin Flavonoids Marine peptides

Covalent flavoproteins:types,occurrence,biogenesis and catalytic mechanisms

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Chinese Journal of natural Medicines 2022年第10期20卷 749-760页

作者： WANG Minjun ZHANG Wenyuan WANG Nan Ocean College Zhejiang UniversityZhoushan 316021China

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin:flavin adenine dinucleotide(FAD)or flavin mononucleotide(FMN).Flavoproteins are involved in a wide array of biological processes,such as photosynthesis,DNA repair and natural product biosynthesis.It should be noted that 5%-10%of flavoproteins have a covalently linked flavin prosthetic group.Such covalent linkages benefit the holoenzyme in several ways including improving the stability and catalytic potency.During the past decade,significant progress has been made in covalent flavoproteins,especially with respect to enzyme-dependent biogenesis and discovery of novel linkage types.The present review gives a condensed overview of investigations published from March 2009 to December 2021,with emphasis on the discovery,biogenesis and their catalytic role in natural product biosynthesis.

关键词： Flavoprotein Covalent linkage Biosynthesis natural products

Screening potential P-glycoprotein inhibitors by combination of a detergent-free membrane protein extraction with surface plasmon resonance biosensor

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Acta Pharmaceutica Sinica B 2022年第7期12卷 3113-3123页

作者： Yuhong Cao Jiahao Fang Yiwei Shi Hui Wang Xiaofei Chen Yue Liu Zhenyu Zhu Yan Cao Zhanying Hong Yifeng Chai School of Pharmacy Second Military Medical UniversityShanghai Key Laboratory for Pharmaceutical Metabolites ResearchShanghai 200433China Zhejiang Institute for Food and Drug Control Hangzhou 310057China

P-glycoprotein(P-gp)highly expressed in cancer cells can lead to multidrug resistance(MDR)and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment.In this study,we established a label-free and detergent-free system combining surface plasmon resonance(SPR)biosensor with styrene maleic acid(SMA)polymer membrane proteins(MPs)stabilization technology to screen potential P-gp inhibitors.First,P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes(SMALPs).Following that,SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system,and the affinity between P-gp and small molecule ligand was determined.The methodological investigation proved that the screening system had good specificity and stability.Nine P-gp ligands were screened out from 50 natural products,and their affinity constants with P-gp were also determined.The in vitro cell verification experiments demonstrated that tetrandrine,fangchinoline,praeruptorin B,neobaicalein,and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin(Adr).Moreover,tetrandrine,praeruptorin B,and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp.This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system.SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp.The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.

关键词： Styrene maleic acid P-Glycoprotein Surface plasmon resonance Membrane proteins Inhibitor screening Affinity calculation natural products Multidrug resistance

Heterologous production of bioactive xenoacremone analogs in Aspergillus nidulans

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Chinese Journal of natural Medicines 2023年第6期21卷 436-442页

作者： LIU Zhiguo LI Wei ZHANG Peng SUN Yi YIN Wen-Bing State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China

Tyrosine-decahydrofluorene derivatives are a class of hybrid compounds that integrate the properties of polyketides and nonribosomal peptides.These compounds feature a[6.5.6]tricarbocyclic core and a para-cyclophane ether moiety in their structures and exhibit anti-tumor and anti-microbial activities.In this study,we constructed the biosynthetic pathway of xenoacremones from Xenoacremonium sinensis ML-31 in the Aspergillus nidulans host,resulting in the identification of four novel tyrosine-decahydrofluorene analogs,xenoacremones I–L(1-4),along with two known analogs,xenoacremones A and B.Remarkably,compounds 3 and 4 contained a 12-membered para-cyclophane ring system,which is unprecedented among tyrosine-decahydrofluorene analogs in X.sinensis.The successful reconstruction of the biosynthetic pathway and the discovery of novel analogs demonstrate the utility of heterologous expression strategy for the generation of structurally diverse natural products with potential biological activities.

关键词： Heterologous expression Xenoacremones Tyrosine-decahydrofluorene PKS-NRPS natural products

Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury

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Neural Regeneration Research 2022年第5期17卷 1080-1087页

作者： Rui Zhao Xue Wu Xue-Yuan Bi Hao Yang Qian Zhang College of Pharmacy Shaanxi University of Chinese MedicineXi’anShaanxi ProvinceChina Key Laboratory of the Ministry of Education for Medicinal Resources and natural Pharmaceutical Chemistry National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest ChinaCollege of Life SciencesShaanxi Normal UniversityXi’anShaanxi ProvinceChina Translational Medicine Center Hong Hui HospitalXi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Department of Pharmacy Hong Hui HospitalXi’an Jiaotong UniversityXi’anShaanxi ProvinceChina

Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases.However,the mechanism behind the neuroprotective effects remains unclear.In this study,rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin.The results revealed that Baicalin greatly increased the Basso,Beattie,Bresnahan Locomotor Rating Scale score,reduced blood-spinal cord barrier permeability,decreased the expression of Bax,Caspase-3,and nuclear factorκB,increased the expression of Bcl-2,and reduced neuronal apoptosis and pathological spinal cord injury.SH-SY5 Y cell models of excitotoxicity were established by application of 10 m M glutamate for 12 hours and then treated with 40μM Baicalin for 48 hours to investigate the mechanism of action of Baicalin.The results showed that Baicalin reversed tight junction protein expression tendencies(occludin and ZO-1)and apoptosis-related protein expression(Bax,Bcl-2,Caspase-3,and nuclear factor-κB),and also led to up-regulation of PI3 K and Akt phosphorylation.These effects on Bax,Bcl-2,and Caspase-3 were blocked by pretreatment with the PI3 K inhibitor LY294002.These findings suggest that Baicalin can inhibit bloodspinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis,possibly by activating the PI3 K/Akt signaling pathway.This study was approved by Animal Ethics Committee of Xi'an Jiaotong University on March 6,2014.

关键词： apoptosis baicalin blood-spinal cord barrier natural products neuron PI3K/Akt signaling pathway spinal cord injury tight junction

Total Synthesis of UCS1025A via Tandem Carbonylative Stille Cross Coupling and Diels-Alder Reactiont

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Chinese Journal of Chemistry 2023年第22期41卷 3019-3024页

作者： Chengsen Cui Mingi Dai Deparment of Chemistry and Center for Cancer Research Purdue University West Lfaytte IN 47907United States Department of Chemistry Emory UniversityAtlantaGA 30322United States

We report an efficient and convergent strategy for the total synthesis of UCS1025A and its diastereomer tetra-epi-UCS1025A.Ucs1025A is a representative member of the naturally occurring pyrrolizidinone polyketides,from which members with potent antibacterial,antifungal,and anticancer activities have been identified.Our approach features a tandem carbonylative Stille cross coupling and Diels-Alder reaction to forge a key C-C bond and build the trans-decalin system.This tandem process utilizes carbon monoxide as a one-carbon linchpin to stitch a vinyl triflate and a vinylstannane together and form the desired enone moiety for the subsequent intramolecular Diels-Alder cyclization.Our synthesis also provides a versatile approach for the synthesis of other related pyrrolizidinone-containing polyketides.

关键词： natural products Total synthesis UCS1025A Carbonylation Diels-Alder reaction Tandem reaction

The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer's disease:a narrative review

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Neural Regeneration Research 2023年第12期18卷 2582-2591页

作者： Qian Zhang Yaping Yan National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China Key Laboratory of Medicinal Resources and Natural Pharmaceutical ChemistryThe Ministry of EducationCollege of Life SciencesShaanxi Normal UniversityXi’anShaanxi ProvinceChina

Alzheimer's disease is a neurodegenerative disease that affects a large proportion of older adult people and is characterized by memory loss,progressive cognitive impairment,and various behavioral disturbances.Although the pathological mechanisms underlying Alzheimer's disease are complex and remain unclear,previous research has identified two widely accepted pathological characteristics:extracellular neuritic plaques containing amyloid beta peptide,and intracellular neurofibrillary tangles containing tau.Furthermore,research has revealed the significant role played by neuroinflammation over recent years.The inflammatory microenvironment mainly consists of microglia,astrocytes,the complement system,chemokines,cytokines,and reactive oxygen intermediates;collectively,these factors can promote the pathological process and aggravate the severity of Alzheimer's disease.Therefore,the development of new drugs that can target neuroinflammation will be a significant step forward for the treatment of Alzheimer's disease.Flavonoids are plant-derived secondary metabolites that possess various bioactivities.Previous research found that multiple natural flavonoids could exert satisfactory treatment effects on the neuroinflammation associated with Alzheimer's disease.In this review,we describe the pathogenesis and neuroinflammatory processes of Alzheimer's disease,and summarize the effects and mechanisms of 13 natural flavonoids(apigenin,luteolin,naringenin,quercetin,morin,kaempferol,fisetin,isoquercitrin,astragalin,rutin,icariin,mangiferin,and anthocyanin)derived from plants or medicinal herbs on neuroinflammation in Alzheimer's disease.As an important resource for the development of novel compounds for the treatment of critical diseases,it is essential that we focus on the exploitation of natural products.In particular,it is vital that we investigate the effects of flavonoids on the neuroinflammation associated with Alzheimer's disease in greater detail.

关键词： Alzheimer's disease astrocytes flavonoids microglia natural products neuroinflammation