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Gut microbiome:A revolution in typeⅱdiabetes mellitus

World Journal of diabetes 2024年第9期15卷 1874-1888页

作者： Madhan Jeyaraman Tejaswin Mariappan Naveen Jeyaraman Sathish Muthu Swaminathan Ramasubramanian Gabriel Silva Santos Lucas Furtado da Fonseca JoséFábio Lana Department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennai 600077Tamil NaduIndia Department of Orthopaedics Brazilian Institute of Regenerative MedicineIndaiatuba 13334-170São PauloBrazil Department of Orthopaedics Orthopaedic Research GroupCoimbatore 641045Tamil NaduIndia Department of Community Medicine Government Stanley Medical College and HospitalChennai 600001Tamil NaduIndia Department of Orthopaedics Government Medical CollegeKarur 639004Tamil NaduIndia Department of Biotechnology Faculty of EngineeringKarpagam Academy of Higher EducationCoimbatore 641021Tamil NaduIndia Department of Orthopaedics Government Medical CollegeOmandurar Government EstateChennai 600002Tamil NaduIndia

typeⅱdiabetes mellitus(T2DM)has experienced a dramatic increase globally across countries of various income levels over the past three *** persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental *** numerous pharmaceutical therapies have been developed,there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse *** this context,the exploration of the gut microbiome presents a promising *** has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals,suggesting its potential role in the disease’s pathogenesis and *** emerging field offers diverse applications,particularly in modifying the gut environment through the administration of prebiotics,probiotics,and fecal microbiome *** interventions aim to restore a healthy microbiome balance,which could potentially alleviate or even reverse the metabolic dysfunctions associated with *** current results from clinical trials have not yet shown dramatic effects on diabetes management,the groundwork has been laid for deeper *** and future clinical trials are critical to advancing our understanding of the microbiome’s impact on *** further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism,researchers can develop more targeted *** potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM,potentially reducing the disease’s burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic,systemic health improvements.

关键词： typeⅱdiabetes Gut microbiome Probiotics Prebiotics Fecal microbiota transplantation

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Mimicking natural cholesterol assimilation to elevate the oral delivery of liraglutide for type Ⅱ diabetes therapy

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Asian Journal of Pharmaceutical Sciences 2022年第5期17卷 653-665页

作者： Ruinan Wu Zhanghan Wu Liyun Xing Xi Liu Lei Wu Zhou Zhou Lian Li Yuan Huang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡ***,administration of GLP-RA is mainly through repetitive subcutaneous injection,which may seriously decrease the compliance and ***,a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide(Lira),a kind of GLP-1 RA,by mimicking the natural cholesterol assimilation.25-hydroxycholesterol(25HC),a cholesterol derivative,was modified on the surfaced of Lira-loaded PLGA nanoparticles(Lira 25HC NPs)and functioned as a“top-down”actuator to facilitate unidirectional transcytosis across the intestinal *** oral delivery,Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on typeⅱdiabetes db/db mice,as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance,repressed weight growth,improved liver glucose metabolism,decreased fasting blood glucose,HbA 1c,serum lipid,and increasedβcells ***,the fasting blood glucose,liver glucose metabolism,and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free *** mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1(NPC1L1)and then basolateral ATP binding cassette transporter A1(ABCA1)overexpressed on the opposite side of intestinal *** cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium,thus improving the oral absorption of *** general,this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.

关键词： Glucagon-like peptide-1 Oral delivery Cholesterol assimilation Liraglutide typeⅱdiabetes HbA 1c

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Design, Synthesis and SAR Studies of Novel and Potent Dipeptidyl Peptidase 4 Inhibitors

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Chinese Journal of Chemistry 2021年第1期39卷 115-120页

作者： Na Luo Xiaoyu Fang Mingbo Su Xinwen Zhang Dan Li Honglin Li Shiliang Li Zhenjiang Zhao Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and Technology130 Meilong RoadShanghai 200237China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences555 Zhuchongzhi RoadShanghai 201203China Shandong Biopolar Dichang Pharmaceutical Co. LtdRM2306No.786 Linzi AvenueZiboShandong 255400China

Dipeptidyl peptidase 4(DPP-4)is a clinically validated target for the treatment of type 2 diabetes mellitus(T2DM).To discover novel and potent DPP-4 inhibitors,three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]*** the designed compounds,41d-1 was the most po tent one with an IC_(50) value of 16.00 nM.

关键词： typeⅱdiabetes Dipeptidyl peptidaseⅣ Inhibitors Molecular docking Structure-activity relationship

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Role of phenolics as antioxidants,biomolecule protectors and as anti-diabetic factors-Evaluation on bark and empty pods of Acacia auriculiformis

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Asian Pacific Journal of Tropical Medicine 2012年第10期5卷 757-765页

作者： Arumugam Sathya Perumal Siddhuraju Bioresource Technology Lab Department of Environmental SciencesBharathiar University

Objective:To search for an efficient and inexpensive source of phytoconstituents with antioxidant potential and health promoting traits from bark and empty pods of Acacia auriculiformis （***）.Methods:Samples of bark and empty pod extracts were analyzed for bioactives（phenolics,flavonoids and proanthocyanidins） and subjected to free radical scavenging activity on DPPH*,ABTS?,OH?,O2*,and NO along with the determination of reducing power, iron chelating activity and peroxidation *** action of extracts on biomolecules and cell membranes were evaluated by DNA nicking assay and haemolysis inhibition assay respectively,α-amylase andα-glucosidase inhibitory potentials were also determined. Results:All the bioactives analyzed were higher in bark（B） than empty pods（EP）[TPC:B （574.51±16.11）;EP（96.80±3.45） mg GAE/***:B（94.71±7.65）;EP（24（?）87±20.45） mg RE/g. Proanthocyanidins:B（2.81±0.31）;EP（1.25±0.01） mg LE/100 g DM]except *** the extracts showed higher quenching capacity on DPPH and ABTS（DPPH:B（0.21±0.01）;EP（1.51±0.17） g extract/g ***:B（111 519.14±79 340.91）;EP（80 232.55±32 894.12） mmol TE/g） with the FRAP of B（84 515.63±3 350.69） and EP（47 940.79±1 257.60） mmol Fe（（?））/*** chelation was not *** addition,they showed lower quenching activity on OH?（B（48.95±1.72）;EP（34.94±1.62）%） and equivalent quenching on O2?（B（53.47±3.92）;EP（24.41±2.61）%）,NO（B（49.04±5.04）; EP（51.00±5.13）%）,peroxidation inhibition（B（67.50±5.50）;EP（55.l±2.3）%） and antihaemolytic potential（B（87.60±6.84）%） towards authentic antioxidant ***,Empty pod extracts are devoid of antihaemolytic *** the extracts showed dose dependent DNA *** this,bark and empty pod extracts exhibited dual inhibiting potential againstα-amylase andα-glucosidase ***:On summarization,it insinuated that both bark and empty pods can be us

关键词： Phenolics Bark Empty pods Acacia auriculiformis Antioxidant activity typeⅱdiabetes

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3D Pharmacophore Model Construction of Selective DPP-IV Inhibitors and Subsequent Validation and in Silico Screening of New Hits

3D Pharmacophore Model Construction of Selective DPP-IV Inhi...

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2011年全国药物化学学术会议——药物的源头创新

作者： Tianjiao Han~1 Yueqing Li~(1,*) Junfeng Gu~2 Zhi Cao~1 Weijie Zhao~1 Xicheng Wang~2 (1 School of Pharmaceutical Science and Technology,Dalian University of Technology,Dalian 116024, China 2 State Key Laboratory of Structure Analyses for Industrial Equipment,Dalian University of Technology,Dalian,116024,China)

＜正＞The 3D pharmacophore model of DPP-Ⅳinhibitors was established using the Discovery Studio software with the training set of 20 selective DPP-Ⅳ*** best pharmacophore hypothesis（Hypol） consists of one hydrogen-bond acceptor,one hydrophobic point,one positive ionizable feature,one aromatic ring as well as five excluded ***’s validation clearly shows that proposed Hypol has highly predictive ability and can be efficiently used as a 3D query for virtual screening to retrieve potential inhibitors from ZINC *** hit compounds subsequently were docked into the DPP-Ⅳactive site and 21 compounds were obtained based on PLP2 scoring ***,this study will be helpful to screen selective DPP-Ⅳinhibitors and provide scientific basis for de novo design of DPP-Ⅳinhibitors.

关键词： typeⅱdiabetes Dipeptidyl-peptidaseⅣ Discovery Studio Pharmacophore model Database searching

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