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ROS-responsive hydrogels with spatiotemporally sequential delivery of antibacterial and Anti-inflammatory drugs for the repair of MRSA-infected wounds

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Regenerative Biomaterials 2024年第1期3卷 119-131页

作者： Bowen Qiao Jiaxin Wang Lipeng Qiao Aziz Maleki Yongping Liang Baolin Guo Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710049China State Key Laboratory for Mechanical Behavior of Materials Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an 710049China Zanjan Pharmaceutical Nanotechnology Research Center(ZPNRC) Zanjan 45139-56184Iran Department of Orthopaedics The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061People’s Republic of China

For the treatment of MRSA-infected wounds,the spatiotemporally sequential delivery of antibacterial and Anti-inflammatory drugs is a promising strategy.In this study,ROS-responsive HA-PBA/PVA(HPA)hydrogel was prepared by phenylborate ester bond cross-linking between hyaluronic acid-grafted 3-amino phenylboronic acid(HA-PBA)and polyvinyl alcohol(PVA)to achieve spatiotemporally controlled release of two kinds of drug to treat MRSA-infected wound.The hydrophilic antibiotic moxifloxacin(M)was directly loaded in the hydrogel.And hydrophobic curcumin(Cur)with Anti-inflammatory function was first mixed with Pluronic F127(PF)to form Cur-encapsulated PF micelles(Cur-PF),and then loaded into the HPA hydrogel.Due to the different hydrophilic and hydrophobic nature of moxifloxacin and Cur and their different existing forms in the HPA hydrogel,the final HPA/M&Cur-PF hydrogel can achieve different spatiotemporally sequential delivery of the two drugs.In addition,the swelling,degradation,self-healing,antibacterial,Anti-inflammatory,antioxidant property,and biocompatibility of hydrogels were tested.Finally,in the MRSA-infected mouse skin wound,the hydrogel-treated group showed faster wound closure,less inflammation and more collagen deposition.Immunofluorescence experiments further confirmed that the hydrogel promoted better repair by reducing inflammation(TNF-a)and promoting vascular(VEGF)regeneration.In conclusion,this HPA/M&CurPF hydrogel that can spatiotemporally sequential deliver antibacterial and Anti-inflammatory drugs showed great potential for the repair of MRSA-infected skin wounds.

关键词： MRSA-infected wounds spatiotemporally sequential delivery antibacterial Anti-inflammatory

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anti-oxidant and Anti-inflammatory Effects of Ethanol Extract from Polygala sibirica L.var megalopha Fr.on Lipopolysaccharide-Stimulated RAW264.7 Cells

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中国结合医学杂志:英文版 2023年第10期29卷 905-913页

作者： YANG Cheng-liu WANG Shi-bo HE Wen-ping LIU Jin-juan Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province School of Life ScienceJiangsu Normal UniversityXuzhouJiangsu Province221116China

Objective To investigate the anti-oxidant and Anti-inflammatory effects of ethanol extract of Polygala sibirica L.var megalopha Fr.(EEP)on RAW264.7 mouse macrophages.Methods RAW264.7 cells were pretreated with 0–200µg/mL EEP or vehicle for 2 h prior to exposure to 1µg/mL lipopolysaccharide(LPS)for 24 h.Nitric oxide(NO)and prostaglandin(PGE2)production were determined by Griess reagent and enzyme-linked immunosorbent assay(ELISA),respectively.The mRNA levels of inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),tumor necrosis factorα(TNF-α),interleukin-1beta(IL-1β),and IL-6 were determined using reverse transcription polymerase chain reaction(RT-PCR).Western blot assay was used to determine the protein expressions of iNOS,COX-2,phosphorylation of extracellular regulated protein kinases(ERK1/2),c-Jun N-terminal kinase(JNK),inhibitory subunit of nuclear factor Kappa B alpha(IκB-α)and p38.Immunofluorescence was used to observe the nuclear expression of nuclear factor-κB p65(NF-κB p65).Additionally,the anti-oxidant potential of EEP was evaluated by reactive oxygen species(ROS)production and the activities of catalase(CAT)and superoxide dismutase(SOD).The 2,2-diphenyl-1-picrylhydrazyl(DPPH),hydroxyl(OH),superoxide anion(O2−)radical and nitrite scavenging activity were also measured.Results The total polyphenol and flavonoid contents of EEP were 23.50±2.16 mg gallic acid equivalent/100 g and 43.78±3.81 mg rutin equivalent/100 g.With EEP treatment(100 and 150µg/mL),there was a notable decrease in NO and PGE2 production induced by LPS in RAW264.7 cells by downregulation of iNOS and COX-2 mRNA and protein expressions(Panti-oxidant enzymes activ

关键词： Polygala sibirica L.var megalopha Fr. Anti-inflammatory anti-oxidant RAW264.7 cells lipopolysaccharide Chinese medicine

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Anti-inflammatory mechanism of the non-volatile ingredients performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope and cell metabolomics

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Journal of Traditional Chinese Medicine 2024年第2期44卷 260-267页

作者： JING Wenguang LIN Xiaoyu LI Chu ZHAO Xiaoliang CHENG Xianlong WANG Penglong WEI Feng MA Shuangcheng Institute of Control of Chinese Traditional Medicine and Ethnic Medicine National Institutes for Food and Drug ControlBeijing 102629China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 102488China Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Diseases Experimental Research CenterChina Academy of Chinese Medical SciencesBeijing 100700China

OBJECTIVE:To explore the Anti-inflammatory components and mechanism of the non-volatile ingredients of patchouli.METHODS:High performance liquid chromatographyheated electron spray ionization-high resolution mass spectroscope(HPLC-HESI-HRMS)was used to analyze the chemical constituents of the non-volatile ingredients of patchouli.The Anti-inflammatory activity of ingredients was evaluated using lipopolysaccharide(LPS)induced RAW264.7 cell inflammation model,and the antiinflammatory mechanism was investigated using multivariate statistical analysis of cell metabolomics.RESULTS:The non-volatile ingredients of patchouli were characterized by HPLC-HESI-HRMS,and 36 flavonoids and 18 other components were identified.These ingredients of patchouli not only had a good protective effect on the LPS-induced inflammation model of RAW264.7 cells,but also regulated the expression levels of arginine,L-leucine,cholesterol,fructose and sorbitol by down-regulating arginine metabolism,aminoacyl-tRNA biosynthesis,polyol/sorbitol pathway,so as to reduce inflammation and reduce cell damage.CONCLUSION:The non-volatile ingredients of patchouli had good Anti-inflammatory effect and exerted its curative effect by regulating endogenous metabolic pathway to reduce inflammatory response.

关键词： Pogostemon non-volatile ingredients Anti-inflammatory cell metabolomics

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Discovery and identification of EIF2AK2 as a direct key target of berberine for Anti-inflammatory effects

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2138-2151页

作者： Wei Wei Qingxuan Zeng Yan Wang Xixi Guo Tianyun Fan Yinghong Li Hongbin Deng Liping Zhao Xintong Zhang Yonghua Liu Yulong Shi Jingyang Zhu Xican Ma Yanxiang Wang Jiandong Jiang Danqing Song Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Using chemoproteomic techniques,we first identified EIF2AK2,eEF1A1,PRDX3 and VPS4B as direct targets of berberine(BBR)for its synergistically Anti-inflammatory effects.Of them,BBR has the strongest affinity with EIF2AK2 via two ionic bonds,and regulates several key inflammatory pathways through EIF2AK2,indicating the dominant role of EIF2AK2.Also,BBR could subtly inhibit the dimerization of EIF2AK2,rather than its enzyme activity,to selectively modulate its downstream pathways including JNK,NF-κB,AKT and NLRP3,with an advantage of good safety profile.In EIF2AK2 gene knockdown mice,the inhibitory IL-1β,IL-6,IL-18 and TNF-a secretion of BBR was obviously attenuated,confirming an EIF2AK2-dependent Anti-inflammatory efficacy.The results highlight the BBR's network mechanism on Anti-inflammatory effects in which EIF2AK2 is a key target,and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammationrelated disorders.

关键词： Berberine Anti-inflammatory Target identification Chemoproteomic technology Photoaffinity probe EIF2AK2

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Anti-inflammatory and analgesic properties of Moroccan medicinal plants:Phytochemistry,in vitro and in vivo investigations,mechanism insights,clinical evidences and perspectives

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Journal of Pharmaceutical Analysis 2022年第1期12卷 35-57页

作者： Abdelhakim Bouyahya Fatima-Ezzahrae Guaouguaou Nasreddine El Omari Naoual El Menyiy Abdelaali Balahbib Mohamed El-Shazly Youssef Bakri Laboratory of Human Pathologies Biology Department of BiologyFaculty of Sciencesand Genomic Center of Human PathologiesFaculty of Medicine and PharmacyMohammed Ⅴ University in Rabat4014Morocco Mohammed Ⅴ University in Rabat LPCMIOMaterials Science Center(MSC)Ecole Normale SuperieureRabat1014Morocco Laboratory of Histology Embryology and CytogeneticFaculty of Medicine and PharmacyMohammed Ⅴ University in Rabat10100Morocco Department of Biology Faculty of Sciences Dhar El MahrazUniversity Sidi Mohamed Ben AbdellahFez30003Morocco Laboratory of Zoology and General Biology Faculty of SciencesMohammed Ⅴ University in RabatRabat1014Morocco Department of Pharmacognosy Faculty of PharmacyAin-Shams UniversityCairo11566Egypt Department of Pharmaceutical Biology Faculty of Pharmacy and BiotechnologyGerman University in CairoCairo11835Egypt

Moroccan medicinal plants exhibit several pharmacological properties such as antimicrobial,anticancer,antidiabetic,analgesic,and Anti-inflammatory effects,which are related to the presence of numerous bioactive compounds,including phenolic acids,flavonoids,and terpenoids.In the present review,we systematically evaluate previously published reports on the Anti-inflammatory and analgesic effects of Moroccan medicinal plants.The in vitro investigations revealed that Moroccan medicinal plants inhibit several enzymes related to inflammatory processes,whereas in vivo studies noted significant Anti-inflammatory and analgesic effects as demonstrated using different experimental models.Various bioactive compounds exhibiting in vitro and in vivo Anti-inflammatory and analgesic effects,with diverse mechanisms of action,have been identified.Some plants and their bioactive compounds reveal specific secondary metabolites that possess important Anti-inflammatory effects in clinical investigations.Our review proposes the potential applications of Moroccan medicinal plants as sources of Anti-inflammatory and analgesic agents.

关键词： Inflammation Medicinal plants Bioactive compounds Anti-inflammatory Analgesic

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Zinc-based metal organic framework with antibacterial and Anti-inflammatory properties for promoting wound healing

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Regenerative Biomaterials 2022年第1期9卷 163-174页

作者： Yuting Chen Jinhong Cai Dachang Liu Shuhan Liu Doudou Lei Li Zheng Qingjun Wei Ming Gao Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affiliated Hospital of Guangxi Medical UniversityNo.22 Shuangyong RoadQingxiu DistrictNanning 530021China Department of Orthopaedics Trauma and Hand Surgery The First Affiliated Hospital of Guangxi Medical UniversityNo.6 Shuangyong RoadQingxiu DistrictNanning 530021China Guangxi Collaborative Innovation Center of Regenerative Medicine and Medical Bioresource Development and Application The First Affiliated Hospital of Guangxi Medical UniversityNo.22 Shuangyong RoadQingxiu DistrictNanning 530021China Guangxi Key Laboratory of Regenerative Medicine The First Affiliated Hospital of Guangxi Medical UniversityNo.22 Shuangyong RoadQingxiu DistrictNanning 530021China

The synergistic effect of antibacterial and Anti-inflammatory is needed to overcome the problem of wound healing difficulties.Based on the favorable antibacterial and Anti-inflammatory effect of zinc ions(Zn^(2+))and the physicochemical properties of metal organic frameworks(MOFs),we prepared nanosized zinc-based MOF:Zn-BTC with the ability to slowly release Zn^(2+).In cellular levels,Zn-BTC possessed lower toxicity to fibroblasts and enhanced capacity of cell proliferation and migration.It also had good bactericidal effect on multiple drug-resistant bacteria by reducing 41.4%MRSA and 47.2%Escherichia coli.In addition,Zn-BTC also displayed the ability of lowering the expression of antioxidant genes:superoxide dismutase 1,superoxide dismutase 2 and interleukin 6,and enhancing the expression of wound healing genes:transforming growth factors-b and type I collagen.Finally,it also demonstrated that Zn-BTC could effectively improve the skin wound healing of SD rats and had no toxicity on major organs.The favorable biocompatibility,antibacterial and Anti-inflammatory properties of Zn-BTC gave a new insight of designing novel MOFs for promoting skin wound healing.

关键词： zinc ions metal organic framework antibacterial Anti-inflammatory skin wound healing

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Improvement of antibacterial, Anti-inflammatory, and osteogenic properties of OGP loaded Co-MOF coating on titanium implants for advanced osseointegration

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Journal of Materials Science & Technology 2023年第15期146卷 131-144页

作者： Bailong Tao Weiwei Yi Xian Qin Junjie Wu Kai Li Ai Guo Jie Hao Lixue Chen Laboratory Research Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Rehabilitation Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Obstetrics and Gynecology Chongqing Health Center for Women and ChildrenChongqing 401147China Women and Children’s Hospital of Chongqing Medical University Chongqing 401147China Department of Orthopedics The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Orthopedics The Third Affiliated Hospital of Chongqing Medical UniversityChongqing 400016Chin

The bacterial infection,especially for methicillin-resistant Staphylococcus aureus(MRSA),and the associated severe inflammatory response could extremely limit the crosstalk of RAW264.7 cells and mesenchymal stem cells(MSCs)and lead to the undesirable osseointegration of peri–implants.It is highly demanded to modify the surface of titanium(Ti)implant to improve its anti-bacterial and Anti-inflammatory properties and facilitate its disabled osseointegration.Herein,in our study,a multifunctional coating of zeolitic imidazolate frameworks-67 encapsulated osteogenic growth peptide(OGP)(ZO)was fabricated on titanium dioxide nanotubes(TNT)substrates(TNT-ZO)via the electrophoresis deposition(EPD)approach.The TNT-ZO substrates exhibited excellent antibacterial activity indicated by the reactive oxygen species(ROS)generation,outer membrane(OM)and inner membrane(IM)permeabilization change,adenosine triphosphate(ATP)decrease,and intracellular compounds(DNA/RNA)leakage.Importantly,the regulation effects of TNT-ZO coating modified titanium substrates on the RAW264.7-MSCs crosstalk could induce the Anti-inflammatory and osteogenic microenvironment via multiple paracrine signaling of Runx2,BMP2,VEGF,and TGF-β1.The promoted effects of coating structure were investigated in vivo,including antibacterial effect,osteogenic differentiation of mesenchymal stem cells,and anti-inflammation of RAW264.7 cells,as well as infected bone regeneration and repair in bone defect transplantation model.The results demonstrated that MRSA was effectively eliminated by the hydrolysis of ZIF-67 nanoparticles on TNT-ZO substrates.Furthermore,the excellent osseointegration of peri–implants was realized simultaneously by modulating the crosstalk of RAW264.7-MSCs.This study could provide a novel approach to designing a multifunctional coating on the Ti implants for infected bone regeneration in orthopedic applications.

关键词： Titanium implants Osteogenic growth peptide Anti-inflammatory antibacterial activity Osteoimmunomodulation

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Structurally Diverse Sesquiterpenoids from Chloranthus henryi var.hupehensis and Their Anti-inflammatory Activities

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Chinese Journal of Chemistry 2023年第10期41卷 1209-1225页

作者： Dan-Yang Zhang Yun-Ran Hu Hui Yang Ya-Nan Wang Shuai Liu Yun-He Zou Jing-Jing Zhou Peng-Yu Zhuang Xiao-Xia Wang Hang Liu School of Pharmacy North China University of Science and TechnologyTangshanHebei 063210China Department of Pharmacy Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu 210008China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China China Pharmaceutical University Nanjing Drum Tower Hospital NanjingJiangsu 210008China

In this study,27 new sesquiterpenoids:twenty monomers and seven dimers,with diverse structures,along with one known chlora-japonilide F(25)were isolated from the aerial parts of Chloranthus henryi var.hupehensis.Structurally,chlorahupetolides A(1)and B(2),two eudesmane-type merosesquiterpenoids with an undescribed C18 carbon framework,and chlorahupetene E(18)are the first example of dimers comprising two eudesmane sesquiterpenoids bridged by a four-membered ring in the Chloranthus.Their struc-tures were characterized by nuclear magnetic resonance(NMR),electronic circular dichroism(ECD),and X-ray diffraction analysis.In the RAW264.7 macrophages model of inflammation induced by LPS,compounds 12,18,and 25 significantly reduced NO production in a dose dependent manner and without cytotoxicity.The mRNA expression of COX-2 was considerably inhibited by treatments with compounds 12,18,and 25.

关键词： Bioorganic chemistry Chloranthus henryi var.hupehensis Anti-inflammatory X-ray diffraction NMR spectroscopy

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In-vitro antioxidant and Anti-inflammatory activities of ethanol stem-bark extract of Blighia sapida K.D.Koenig

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Journal of Pharmaceutical Analysis 2022年第2期12卷 350-354页

作者： Mukaila B.Adekola Jacob O.Areola Oladapo F.Fagbohun Funke T.Asaolu Gbenga E.Ogundepo Adeniyi O.Fajobi Olubunmi O.Babalola Department of Environmental Management and Toxicology Federal University of AgricultureAbeokuta110001Nigeria Department of Medical Biochemistry Obafemi Awolowo UniversityIle-Ife230001Nigeria Department of Biomedical Engineering First Technical University IbadanOyo StateIbadan200001Nigeria Department of Biochemistry and Molecular Biology Obafemi Awolowo UniversityIle-Ife230001Nigeria

Blighia sapida(B.sapida)K.D.Koenig(Family Sapindaceae)is a branchless straight bole approximately 15 m in length.The study evaluated the antioxidant and Anti-inflammatory activities of ethanol extract and fractions of B.sapida stem-bark using in vitro methods.Ethanol extract and its fractions were investigated for 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging activity,ferric reducing antioxidant power(FRAP),total antioxidant capacity(TAC),and quantitative phenolic and flavonoid contents.Anti-inflammatory activity was evaluated using albumin denaturation and membrane stabilization assays.The extract and its fractions exhibited radical scavenging and Anti-inflammatory properties.The ethyl acetate fraction possessed maximum phenolic and flavonoid contents(136.67±1.55 gallic acid equivalent mg/g and 75.76±4.03 quercetin equivalent mg/g,respectively).antioxidant studies revealed that the ethyl acetate fraction displayed superior activity with an IC_(50)=0.09±0.03 mg/mL DPPH,and values of 146.96±3.81 ascorbic acid equivalent(AAE)mg/g and 359.20±4.98 AAE mg/g for FRAP and TAC,respectively.Furthermore,the Anti-inflammatory activity was revealed by inhibition of heatinduced albumin denaturation and red blood cell membrane stabilization at concentrations of 200 -1000 mg/mL and 50-250 mg/mL,respectively.The ethanol extract and fractions exhibited antioxidant and Anti-inflammatory activities,with ethyl acetate fraction showing superior activity,which could be attributed to secondary metabolites,mainly phenolic compounds.Overall,the antioxidant and antiinflammatory activities of B.sapida can be exploited by ethnomedicinal users.

关键词： Blighia sapida Extract Anti-inflammatory antioxidant Radical scavenging

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A hydrogel spinal dural patch with potential Anti-inflammatory,pain relieving and antibacterial effects

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Bioactive Materials 2022年第8期7卷 389-401页

作者： Jiahao Li Jingjing Tian Chunxu Li Longyun Chen Yu Zhao Department of Orthopaedic Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Medical Science Research Center Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Pathology State Key Laboratory of Complex Severe and Rare DiseaseMolecular Pathology Research CenterPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

CSFL caused by spinal dural defect is a common complication of spinal surgery,which need repair such as suture or sealants.However,low intracranial pressure symptoms,wound infection and prolonged hospital associated with pin-hole leakage or loose seal effect were often occurred after surgical suture or sealants repair.Stable,pressure resistance and high viscosity spinal dural repair patch in wet environment without suture or sealants was highly needed.Herein,a bioactive patch composed of alginate and polyacrylamide hydrogel matrix cross-linked by calcium ions,and chitosan adhesive was proposed.This fabricated patch exhibits the capabilities of promoting defect closure and good tight seal ability with the bursting pressure is more than 790 mm H2O in wet environment.In addition,the chitosan adhesive layer of the patch could inhibit the growth of bacterial in vitro,which is meaningful for the postoperative infection.Furthermore,the patch also significantly reduced the expression of GFAP,IBA-1,MBP,TNF-α,and COX-2 in early postoperative period in vivo study,exerting the effects of Anti-inflammatory,analgesic and adhesion prevention.Thus,the bioactive patch expected to be applied in spinal dural repair with the good properties of withstanding high pressure,promoting defect closure and inhibiting postoperative infection.

关键词： Alginate hydrogel Chitosan adhesive Dural defect repair Anti-inflammatory Bacteriostasis

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