Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase...Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.展开更多
Diabetic retinopathy is a leading cause of blindness among working-age adults.Despite many years of research,treatment options for diabetic retinopathy remain limited and with adverse effects.Discovery of new molecula...Diabetic retinopathy is a leading cause of blindness among working-age adults.Despite many years of research,treatment options for diabetic retinopathy remain limited and with adverse effects.Discovery of new molecular entities with adequate clinical activity for diabetic retinopathy remains one of the key research priorities in ophthalmology.This review is focused on the therapeutic effects of cannabidiol(CBD),a nonpsychoactive native cannabinoid,as an emerging and novel therapeutic modality in ophthalmology based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy-a retinal disease associated with vascular-neuroinflammation.Special emphasis is placed on novel mechanisms which may shed light on the pharmacological activity asso c iated with CBD preclinically.These include a selfdefence system against inflammation and neurodegeneration mediated by inhibition of equilibrat ive nucleoside transporter and activation of adenosine receptor by treatment with CBD.展开更多
Nowadays, there are still many challenges to skin regeneration. As a new type of skin substitute, hydrogel has emerging gradually with its excellent properties. However, it is still a challenge to combine with biologi...Nowadays, there are still many challenges to skin regeneration. As a new type of skin substitute, hydrogel has emerging gradually with its excellent properties. However, it is still a challenge to combine with biological active agents to facilitate skin regeneration. Under the circumstance, we synthesized argininebased poly(ester amide)(Arg-PEA) and hyaluronic acid(HA-MA), and combined them into new hybrid hydrogels via photo-crosslinking. We found that the internal structure and physicochemical properties of hybrid hydrogels were greatly improved with the increase of content of Arg-PEA. Therefore, we designed hybrid hydrogels with 5 wt% and 10 wt% of Arg-PEA content, respectively. Besides, we selected the corresponding anti-inflammatory(CRP, TNF-α) indicators to detect the anti-inflammatory properties of the hybrid hydrogels at the protein level, and the corresponding antioxidant indicators(SOD, GSH/GSSG, MDA)were selected to investigate the antioxidant properties of hybrid hydrogels at the cellular level in vitro.In addition, we also selected relevant genes to test the effect of hybrid hydrogels on fibrosis and vascularization in the process of skin wound healing in vitro and verified them in vivo with a mouse dorsum wound model. The results confirmed that Arg-PEA/HA-MA(AH) hybrid hydrogel was a prospective scaffold material for skin regeneration.展开更多
A novel near-infrared light photothemal-activated H2S-donating nanocomposite hydrogel was developed,through combination of a thermo-labile H2S donor and photothermal nanoparticles in agarose hydrogel.The polyethylenim...A novel near-infrared light photothemal-activated H2S-donating nanocomposite hydrogel was developed,through combination of a thermo-labile H2S donor and photothermal nanoparticles in agarose hydrogel.The polyethylenimine dithiocarbamate polymer,a thermo-labile compound,was synthesized as a novel H2S donor.The combination of a thermo-labile hydrogen sulfide donor and photothermal nanoparticles enabled the generation of H2S in agarose hydrogel upon irradiation with near-infrared light.The ability to modulate the photoirradiation for controlled generation and spatiotemporally release of H2S are its specific advantages.This photothermal spatiotemporally controlled H2S-releasing strategy was successfully applied to anti-inflammation treatment in a rat model,demonstrating its utility as a novel H2S-based therapeutic approach.展开更多
Rosemary(Rosmarius officinalis L.), an endemic plant species in south region of China, is traditionally used as a spice. In this research, the anti-inflammatory activities of essential oil and the antibacterial activi...Rosemary(Rosmarius officinalis L.), an endemic plant species in south region of China, is traditionally used as a spice. In this research, the anti-inflammatory activities of essential oil and the antibacterial activities of ethanol extraction were determined, respectively. Results showed that based on the GC-MS analysis there were 35 kinds of active ingredients in the essential oil in totally, mainly including D-limonene(24.158 ml/L), α-Pinene(23.325 ml/L), Camphor(9.855 ml/L),Camphene(7.076 ml/L), Verbenone(6.685 ml/L), Borneol(5.580 ml/L), etc. The LCUV determination indicated that the main components in the ethanol extractionwere rosmarinic acid(3 910 mg/kg) and carnosic acid(2 970 mg/kg). By mice peritoneal macrophage phagocytosis of chicken erythrocytes experiment, the essential oil of rosemary was shown having a significant role in anti-inflammation. And the ethanol extraction had broad-spectrum antibacterial effects, but had no effect on mold by the agar diffusion method of 8 bacteria. As a result, both rosemary essential oil and ethanol extraction had good potential medicinal values.展开更多
A series of mono L-amino acid ester, mono non-steroid anti-inflammation drug （NSAID）, carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a ＂one pot synthesis＂ method and their in ...A series of mono L-amino acid ester, mono non-steroid anti-inflammation drug （NSAID）, carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a ＂one pot synthesis＂ method and their in vitro anti-HBV activity were evaluated in HepG 2.2.15 cells. Compound 9a exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with IC50 and selective index （SI） values of 0.48μmol/L and 763.72, respectively.展开更多
Aim Forsythia suspensa （Thunb.） Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine （TCM） with heat-clearing and detoxicating properties. In this study, we aimed to stud...Aim Forsythia suspensa （Thunb.） Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine （TCM） with heat-clearing and detoxicating properties. In this study, we aimed to study the antitumor activity of Lianqiao aqueous extract against melanoma using cancer cell line-based in vitro and mouse allografl tumor in vivo models. Furthermore, we also investigated the underlying molecular mechanisms, par- ticularly the involvement of anti-inflammation and anti-oxidation properties in its antitumor activity. Methods The proliferation of cancer cells was measured by MTT assay. The transplanted B16-F10 melanoma in C57BL/6 mice were established and used for the evaluation of in vivo antitumor effect of LQ. Tumor growth was monitored twice a week. Ki67 and CD31 were used to detect cancer cell proliferation and angiogenesis in tumor, respectively. The anti-oxidative property of LQ was determined by measuring the levels of ROS, MDA and GSH. The anti-inflamma- tory effect of LQ was evaluated by measuring TNF-α and IL-6 using ELISA kits. Other protein expression was deter- mined by Western Blot. Results LQ strongly inhibited the growth of B16-F10 cells in vitro and the tumor growth in vivo. The survival time of tumor-bearing mice was significantly prolonged by LQ. LQ inhibited cancer cell prolif- eration and angiogenesis in tumor as evidenced by decreased expressions of Ki67 and CD31. Levels of ROS, MDA TNF-α and IL-6 decreased, while GSH increased in LQ treatment group, indicating a strong anti-oxidative and an- ti-inflammatory activity of LQ. The expression of antioxidant proteins Nff-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by LQ treatment. Conclusions LQ exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of LQ in- volved the decreased oxidative stress and inflammation in tumor, which is closely related to the heat-clearing and detoxicating properties of LQ.展开更多
OBJECTIVE To investigate the therapeutic effects and related signaling pathways involved in the actions of resveratrol on experimental pneumoconiosis in vivo and in vitro.METHODS The pneumoconiosis animal model was in...OBJECTIVE To investigate the therapeutic effects and related signaling pathways involved in the actions of resveratrol on experimental pneumoconiosis in vivo and in vitro.METHODS The pneumoconiosis animal model was induced by exposing male SD rats to 15mg·m-3 silica aerosol in an inhalation chamber system for 6h·d-1,5d·week-1 for up to 8 weeks.The vehicle or resveratrol(10or 20mg·kg-1)was preventively or remedially administered to the rats during or after the 4-or 8-week silica exposure(SE)period,respectively.After 4-,8-,and up to 14-week treatment,in vivo near-infrared fluorescence imaging analysis and histological analysis were performed to evaluate the pathological changes in rat lung.Inflammatory cytokines level in bronchoalveolar lavage fluid(BALF)was measured by ELISA testing,and the deposition of fibrotic collagen proteins in lung parenchyma was determined by western blotting and immunohistochemistry analysis.Microarray analysis was performed to screen the signaling pathways involved in the actions of resveratrol on pneumoconiosis in vitro models.Anti-inflammation action and signaling of resveratrol was evaluated on silica-stimulated rat alveolar macrophage,which is one of the crucial effector cells for silica-induced inflammatory response;anti-fibrosis action and signaling of resveratrol was evaluated on TGF-β-induced human lung fibroblast,which acts as a promoter in the later fibrotic process of pneumoconiosis.RESULTS Silica aerosol exposure significantly increased macrophage infiltration and matrix metalloproteinases activity in lung tissue concomitant with the increased levels of inflammatory mediators in BALF.Preventive treatment with resveratrol(20mg·kg-1·d-1)reversed all these biochemical indices as well as histopathological alterations induced by silica exposure.Post-SE resveratrol treatment mildly reduced silica-induced inflammatory response in rat lung with no statistical significance.In vitro study revealed that resveratrol could inhibit alveolar macrophage cell death and decrease the levels of IL-1β and TNF-αinduced by silica particle exposure to cultured alveolar macrophages.Resveratrol was further shown to inhibit the nuclear transition of NF-κB and formation of cleaved caspase-1.Encouragingly,resveratrol preventively attenuated the lung fibrosis,evidenced by less fibrotic nodules formation and collagen proteins expression.No significant improvement on lung fibrosis was observed with post-SE resveratrol treatment.Invitrostudy further demonstrated that resveratrol suppressed TGF-β-induced lung fibroblast proliferation and collagen deposition,concomitant with the depressed activity of TGF-β/Smad signaling in lung fibroblast.CONCLUSION Resveratrol shows the anti-inflammation and anti-fibrosis actions on experimental pneumoconiosis in vivo and in vitro models.The depression of NF-κB,NALP3-inflammasome,and TGF-β/Smad signaling pathways may be involved in the anti-inflammation and anti-fibrosis actions of resveratrol,respectively.Resveratrol could be a potential therapeutic agent for the intervention of pneumoconiosis.展开更多
The ocean possesses a complex setting with high pressure,high salinity,oligotrophy,low temperature and weak illumination conditions.To survive and evolve in such harsh surroundings,marine organisms metabolize a series...The ocean possesses a complex setting with high pressure,high salinity,oligotrophy,low temperature and weak illumination conditions.To survive and evolve in such harsh surroundings,marine organisms metabolize a series of chemicals known as secondary metabolites which indicate structural and functional diversity to adapt interspecific survival competition.During recent decades,the anti-inflammatory property of marine natural products has come under scrutiny as inflammation involves in the vast majority of diseases.Correspondingly,a myriad of marine bioactive molecules including terpenes,polypeptides,polysaccharides,sterols and many others may bring a new insight into inflammation therapies with multifarious sources and minimal side effects.And a better understanding of their mechanisms of anti-inflammation may lead to better treatments for numerous diseases.Herein,the research progress of marine-derived anti-inflammation compounds and the relevant mechanisms were reviewed,to provide a basis for the research and development of anti-inflammatory marine drugs.展开更多
Parkinson’s disease（PD）is characterized by the progressive loss of midbrain dopaminergic（m DA）neurons and a subsequent decrease in striatal dopamine levels,which cause the typical clinical motor symptoms such as ...Parkinson’s disease（PD）is characterized by the progressive loss of midbrain dopaminergic（m DA）neurons and a subsequent decrease in striatal dopamine levels,which cause the typical clinical motor symptoms such as muscle rigidity,bradykinesia and tremor.展开更多
Cartilage tissue engineering offers hope for tracheal cartilage defect repair.Establishing an anti-inflammatory microenvironment stands as a prerequisite for successful tracheal cartilage restoration,especially in imm...Cartilage tissue engineering offers hope for tracheal cartilage defect repair.Establishing an anti-inflammatory microenvironment stands as a prerequisite for successful tracheal cartilage restoration,especially in immunocompetent animals.Hence,scaffolds inducing an anti-inflammatory response before chondrogenesis are crucial for effectively addressing tracheal cartilage defects.Herein,we develop a shell–core structured PLGA@ICA-GT@KGN nanofilm using poly(lactic-co-glycolic acid)(PLGA)and icariin(ICA,an antiinflammatory drug)as the shell layer and gelatin(GT)and kartogenin(KGN,a chondrogenic factor)as the core via coaxial electrospinning technology.The resultant PLGA@ICA-GT@KGN nanofilm exhibited a characteristic fibrous structure and demonstrated high biocompatibility.Notably,it showcased sustained release characteristics,releasing ICA within the initial 0 to 15days and gradually releasing KGN between 11 and 29days.Subsequent in vitro analysis revealed the potent anti-inflammatory capabilities of the released ICA from the shell layer,while the KGN released from the core layer effectively induced chondrogenic differentiation of bone marrow stem cells(BMSCs).Following this,the synthesized PLGA@ICA-GT@KGN nanofilms were loaded with BMSCs and stacked layer by layer,adhering to a‘sandwich model’to form a composite sandwich construct.This construct was then utilized to repair circular tracheal defects in a rabbit model.The sequential release of ICA and KGN facilitated by the PLGA@ICA-GT@KGN nanofilm established an anti-inflammatory microenvironment before initiating chondrogenic induction,leading to effective tracheal cartilage restoration.This study underscores the significance of shell–core structured nanofilms in temporally regulating anti-inflammation and chondrogenesis.This approach offers a novel perspective for addressing tracheal cartilage defects,potentially revolutionizing their treatment methodologies.展开更多
Background:The aim was to elucidate the function of IL-37 in middle east respiratory syndrome coronavirus(MERS-CoV)infection,thereby providing a novel therapeutic strategy for managing the clinical treatment of inflam...Background:The aim was to elucidate the function of IL-37 in middle east respiratory syndrome coronavirus(MERS-CoV)infection,thereby providing a novel therapeutic strategy for managing the clinical treatment of inflammatory response caused by respiratory virus infection.Methods:We investigated the development of MERS by infecting hDPP4 mice with hCoV-EMC(107 TCID50[50%tissue culture infectious dose])intranasally.We infected A549 cells with MERS-CoV,which concurrently interfered with IL-37,detecting the viral titer,viral load,and cytokine expression at certain points postinfection.Meanwhile,we administered IL-37(12.5μg/kg)intravenously to hDPP4 mice 2 h after MERS-CoV-2 infection and collected the serum and lungs 5 days after infection to investigate the efficacy of IL-37 in MERS-CoV infection.Results:The viral titer of MERS-CoV-infected A549 cells interfering with IL-37 was significantly reduced by 4.7-fold,and the viral load of MERS-CoV-infected hDPP4 mice was decreased by 59-fold in lung tissue.Furthermore,the administration of IL-37 suppressed inflammatory cytokine and chemokine(monocyte chemoattractant protein 1,interferon-γ,and IL-17A)expression and ameliorated the infiltration of inflammatory cells in hDPP4 mice.Conclusion:IL-37 exhibits protective properties in severe pneumonia induced by MERS-CoV infection.This effect is achieved through attenuation of lung viral load,suppression of inflammatory cytokine secretion,reduction in inflammatory cell infiltration,and mitigation of pulmonary injury.展开更多
In this paper,the anti-tumor,anti-inflammatory,antibacterial and anti-asthma effects of isobavachalcone and their molecular mechanisms were reviewed to provide theoretical support for further research of isobavachalco...In this paper,the anti-tumor,anti-inflammatory,antibacterial and anti-asthma effects of isobavachalcone and their molecular mechanisms were reviewed to provide theoretical support for further research of isobavachalcone and development of new drugs.展开更多
Ten novel xanthones,garpedunxanthones A-G(1-5,6a/6b,7a/7b) and nujiangxanthone Q(8),along with sixteen known analogs(9-24),were isolated from Garcinia pedunculata and G.nujiangensis.Their structures were elucidated th...Ten novel xanthones,garpedunxanthones A-G(1-5,6a/6b,7a/7b) and nujiangxanthone Q(8),along with sixteen known analogs(9-24),were isolated from Garcinia pedunculata and G.nujiangensis.Their structures were elucidated through high-resolution electrospray ionization mass spectrometry(HR-ESI-MS) data,comprehensive nuclear magnetic resonance(NMR) spectroscopic analyses,and electronic circular dichroism(ECD) calculations.All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide(NO) production in lipopolysaccharide(LPS)-induced RAW264.7cells.Structure-activity relationships are also discussed.Compounds 7b,19,and 21 exhibited significant anti-inflammatory activity with IC_(50) values of 16.44±0.69,14.28±0.78,and 10.67±3.28 μmol·L^(-1),respectively.Enzyme-linked immunosorbent assay(ELISA) demonstrated that compounds 7b,19,and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner.The inhibitory effect of compo und 21 on IL-6 at 20 μmol·L^(-1)was comparable to that of the positive control.In network pharmacology studies,potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation,including positive regulation of mitogen-activated protein kinase(MAPK) cascade,protein kinase activity,NO synthase regulator activity,MAPK signaling pathway,and EGFR tyrosine kinase inhibitor resistance.展开更多
The inflammatory response is a crucial physiological process that can lead to tissue damage and is considered a causative factor for various chronic diseases,such as rheumatoid arthritis.Recent research has focused on...The inflammatory response is a crucial physiological process that can lead to tissue damage and is considered a causative factor for various chronic diseases,such as rheumatoid arthritis.Recent research has focused on exploring valuable nutrients derived from Cannabis sativa L.(hemp)seeds,particularly hemp seed proteins.Therefore,this study aimed to investigate the release of anti-inflammatory peptides from Lactobacillus paraplantarum-fermented hemp seed proteins.To confirm the complete hydrolysis of hemp seed proteins during the fermentation process,sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)was employed.Further,the isolation and purification of peptides were achieved through ultrafiltration.The identity of peptides was nextly established using ultra-high performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS).The results revealed a total of 39 identified peptides in fermented hemp seeds,with 9 peptides selected based on their relative quantity.Notably,AAELIGVP(P1),AAVPYPQ(P2),VFPEVAP(P4),DVIGVPLG(P6),and PVPKVL(P9)demonstrated strong anti-inflammatory abilities in lipopolysaccharide(LPS)-induced RAW264.7 macrophage cells.Molecular docking was used to understand the potential anti-inflammatory mechanism of these 5 peptides,and in silico results indicated that P1,P2,P4,P6,and P9 could bind to the active sites of toll-like receptor 4(TLR-4),nuclear factor-κB(NF-κB),and inhibitor of NF-κB kinase(IKK)with higher binding energies.Overall,these findings indicate that hemp seeds have potential to be a source of bioactive peptides for functional foods with anti-inflammatory properties.展开更多
This study aimed to investigate the anti-inflammatory properties and underlying molecular mechanisms of 2,4',5'-trihydroxyl-5,2'-dibromo diphenylmethanone(LM49)using a carrageenan-induced paw edema model i...This study aimed to investigate the anti-inflammatory properties and underlying molecular mechanisms of 2,4',5'-trihydroxyl-5,2'-dibromo diphenylmethanone(LM49)using a carrageenan-induced paw edema model in mice,which serves as a well-established model for acute inflammation.Mice were randomly assigned into six groups,and acute inflammation was induced by injecting 1%carrageenan solution into the paw.To elucidate the anti-inflammatory effects and mechanisms of LM49,a comprehensive approach was employed,including pathology,transcriptomics,flow cytometry,RT-qPCR,Western blotting analysis,and molecular docking analysis.The results demonstrated that LM49 exerted a significant protective effect by reducing paw edema and lowering serum levels of pro-inflammatory cytokines IL-1βand TNF-a,while concurrently elevating anti-inflammatory cytokine IL-10 levels.Transcriptomic analysis identified 453 differentially expressed genes in the LM49-treated group.KEGG and GO enrichment analyses indicated that LM49 suppressed the NF-kB signaling pathway and modulated several other immuneinflammatory pathways.Molecular docking studies identified eight key targets of LM49 within the NF-kB signaling pathway.Furthermore,Western blotting analysis confirmed that LM49 inhibited the phosphorylation of p65 and IB-αand downregulated the expression of MYD88 and TLR4 in mouse paw tissues.These findings provided a foundational understanding of the anti-inflammatory effects and molecular mechanisms of LM49,paving the way for further in-depth studies in this field.展开更多
Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer.At present,most of wound repair materials are passive and can’t response to t...Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer.At present,most of wound repair materials are passive and can’t response to the wound microenvironment,resulting in a low utilization of bioactive substances and hence a poor therapeutic effect.Therefore,it’s essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality.In this work,metformin-laden CuPDA NPs composite hydrogel(Met@CuPDA NPs/HG)was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine(Gel-DA),Cu-loaded polydopamine nanoparticles(CuPDA NPs)with hyaluronic acid modified by phenyl boronate acid(HA-PBA),which possessed good injectability,self-healing,adhesive and DPPH scavenging performance.The slow release of metformin was achieved by the interaction with CuPDA NPs,boric groups(B-N coordination)and the constraint of hydrogel network.Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently.Moreover,CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of>95%within 10 min and also the slow release of Cu^(2+)to protect wound from infection for a long time.Met@CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu^(2+).More importantly,Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway.Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria,inhibiting inflammation,improving angiogenesis and accelerating the deposition of ECM and collagen.Therefore,Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.展开更多
Objective To investigate the inhibitory effect of Tripterygium wilfordii polycoride（TWP） towards the pro-inflammatory factors（TNF-α and IL-1β） on the inflammatory reaction in macrophages induced by LPS and its r...Objective To investigate the inhibitory effect of Tripterygium wilfordii polycoride（TWP） towards the pro-inflammatory factors（TNF-α and IL-1β） on the inflammatory reaction in macrophages induced by LPS and its regulatory effect and influence on the inflammation via TLR4/NF-k B. Methods The MTT method was adopted to test the effect of drugs, TWP, dexamethasone（DXM） and azathioprine（AZA） on cell growth and to select the appropriate concentration. LPS was used to induce the inflammatory reaction in RAW264.7 cell line of mice. Elisa kit was adopted to test the levels of TNF-α and IL-1β. Western blotting was adopted to test the protein expression of TNF-α and IL-1β. RT-PCR was adopted to test the expression of TLR4 and NF-κB. Results The inhibiting effect of TWP on the release of TNF-α and IL-1β in a dose dependent manner. The inhibitory effect of three different TWP dose groups is weaker than that in DXM group. However, TWP in high dose is better than AZA on TNF-α and is as strong as AZA on IL-1β. The dose dependent manner also exits in the effect on the expression of TLR4 and NF-κB, the effect is not weaker, but even stronger than that of DXM and AZA. Conclusion The research shows that down regulation of TLR4 and NF-k B p65 may be one of the mechanisms about the TWP inhibitory effect on TNF-α and IL-1β.展开更多
The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alz...The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.展开更多
The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and diversity.Previous studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket...The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and diversity.Previous studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket of protein kinase B(AKT),and swertiamarin(Swe)acts on the pleckstrin homology(PH)domain of AKT.However,the combined synergistic effect of relieving the inflammatory response has yet to be elucidated.Based on high sensitivity,specificity and fast-responsibility fluorescent sensors,the Förster resonance energy transfer(FRET)technique offers a route to provide clear insights into physiological and pathological processes.In the study,molecular docking,the fluorescent probes of Phi and Swe for FRET were designed and synthesized.FRET analysis shown that Swe and Phi concurrently acted on the PH domain and allosterically inhibited pocket of AKT,respectively.The combination of Swe and Phi significantly increased the heat stability of AKT and decreased protease-induced degeneration.In lipopolysaccharides(LPS)-induced mice and cells,the combination arrested AKT activation,nuclear factor kappa-B(NF-κB)phosphorylation,and the expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8.In conclusion,FRET revealed Phi and Swe concurrently targeted AKT on different domains and the combination of Phi and Swe enhanced the anti-inflammatory effect.展开更多
基金supported in part by grants from the Young Scientists Awards Foundation of Shandong Province of China,No.BS2013YY049the China Postdoctoral Science Foundation,No.2012M511036
文摘Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.
文摘Diabetic retinopathy is a leading cause of blindness among working-age adults.Despite many years of research,treatment options for diabetic retinopathy remain limited and with adverse effects.Discovery of new molecular entities with adequate clinical activity for diabetic retinopathy remains one of the key research priorities in ophthalmology.This review is focused on the therapeutic effects of cannabidiol(CBD),a nonpsychoactive native cannabinoid,as an emerging and novel therapeutic modality in ophthalmology based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy-a retinal disease associated with vascular-neuroinflammation.Special emphasis is placed on novel mechanisms which may shed light on the pharmacological activity asso c iated with CBD preclinically.These include a selfdefence system against inflammation and neurodegeneration mediated by inhibition of equilibrat ive nucleoside transporter and activation of adenosine receptor by treatment with CBD.
基金supported by the National Natural Science Foundation of China (No. 52103039)Sichuan University postdoctoral interdisciplinary Innovation Fund。
文摘Nowadays, there are still many challenges to skin regeneration. As a new type of skin substitute, hydrogel has emerging gradually with its excellent properties. However, it is still a challenge to combine with biological active agents to facilitate skin regeneration. Under the circumstance, we synthesized argininebased poly(ester amide)(Arg-PEA) and hyaluronic acid(HA-MA), and combined them into new hybrid hydrogels via photo-crosslinking. We found that the internal structure and physicochemical properties of hybrid hydrogels were greatly improved with the increase of content of Arg-PEA. Therefore, we designed hybrid hydrogels with 5 wt% and 10 wt% of Arg-PEA content, respectively. Besides, we selected the corresponding anti-inflammatory(CRP, TNF-α) indicators to detect the anti-inflammatory properties of the hybrid hydrogels at the protein level, and the corresponding antioxidant indicators(SOD, GSH/GSSG, MDA)were selected to investigate the antioxidant properties of hybrid hydrogels at the cellular level in vitro.In addition, we also selected relevant genes to test the effect of hybrid hydrogels on fibrosis and vascularization in the process of skin wound healing in vitro and verified them in vivo with a mouse dorsum wound model. The results confirmed that Arg-PEA/HA-MA(AH) hybrid hydrogel was a prospective scaffold material for skin regeneration.
基金financial support of the National Natural Science Foundation of China(Nos.21735002,21575037,21778016,21675046,21877030)Natural Science Foundation of Hunan Province(No.2177JJ3026)Keypoint Research and Invention Program of Hunan Province(No.2017DK2011)。
文摘A novel near-infrared light photothemal-activated H2S-donating nanocomposite hydrogel was developed,through combination of a thermo-labile H2S donor and photothermal nanoparticles in agarose hydrogel.The polyethylenimine dithiocarbamate polymer,a thermo-labile compound,was synthesized as a novel H2S donor.The combination of a thermo-labile hydrogen sulfide donor and photothermal nanoparticles enabled the generation of H2S in agarose hydrogel upon irradiation with near-infrared light.The ability to modulate the photoirradiation for controlled generation and spatiotemporally release of H2S are its specific advantages.This photothermal spatiotemporally controlled H2S-releasing strategy was successfully applied to anti-inflammation treatment in a rat model,demonstrating its utility as a novel H2S-based therapeutic approach.
基金Department of Fermentation Research of Institute of Bio-engineering from Henan University of Technology for providing strains and Key Scientific Research Project of Henan province in China (No.102102310027) for financial support
文摘Rosemary(Rosmarius officinalis L.), an endemic plant species in south region of China, is traditionally used as a spice. In this research, the anti-inflammatory activities of essential oil and the antibacterial activities of ethanol extraction were determined, respectively. Results showed that based on the GC-MS analysis there were 35 kinds of active ingredients in the essential oil in totally, mainly including D-limonene(24.158 ml/L), α-Pinene(23.325 ml/L), Camphor(9.855 ml/L),Camphene(7.076 ml/L), Verbenone(6.685 ml/L), Borneol(5.580 ml/L), etc. The LCUV determination indicated that the main components in the ethanol extractionwere rosmarinic acid(3 910 mg/kg) and carnosic acid(2 970 mg/kg). By mice peritoneal macrophage phagocytosis of chicken erythrocytes experiment, the essential oil of rosemary was shown having a significant role in anti-inflammation. And the ethanol extraction had broad-spectrum antibacterial effects, but had no effect on mold by the agar diffusion method of 8 bacteria. As a result, both rosemary essential oil and ethanol extraction had good potential medicinal values.
基金supported by the National Natural Science Foundation of China(Nos.20962004,81260473)Projects of Guizhou Science and Technology Department(Nos.2013-3031,2012-3013)Excellent Youth Scientific Talents Foundation of Guizhou(No.2013-45)
文摘A series of mono L-amino acid ester, mono non-steroid anti-inflammation drug （NSAID）, carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a ＂one pot synthesis＂ method and their in vitro anti-HBV activity were evaluated in HepG 2.2.15 cells. Compound 9a exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with IC50 and selective index （SI） values of 0.48μmol/L and 763.72, respectively.
文摘Aim Forsythia suspensa （Thunb.） Vahl, Lianqiao in Chinese, is one of the most fundamental herbs in traditional Chinese medicine （TCM） with heat-clearing and detoxicating properties. In this study, we aimed to study the antitumor activity of Lianqiao aqueous extract against melanoma using cancer cell line-based in vitro and mouse allografl tumor in vivo models. Furthermore, we also investigated the underlying molecular mechanisms, par- ticularly the involvement of anti-inflammation and anti-oxidation properties in its antitumor activity. Methods The proliferation of cancer cells was measured by MTT assay. The transplanted B16-F10 melanoma in C57BL/6 mice were established and used for the evaluation of in vivo antitumor effect of LQ. Tumor growth was monitored twice a week. Ki67 and CD31 were used to detect cancer cell proliferation and angiogenesis in tumor, respectively. The anti-oxidative property of LQ was determined by measuring the levels of ROS, MDA and GSH. The anti-inflamma- tory effect of LQ was evaluated by measuring TNF-α and IL-6 using ELISA kits. Other protein expression was deter- mined by Western Blot. Results LQ strongly inhibited the growth of B16-F10 cells in vitro and the tumor growth in vivo. The survival time of tumor-bearing mice was significantly prolonged by LQ. LQ inhibited cancer cell prolif- eration and angiogenesis in tumor as evidenced by decreased expressions of Ki67 and CD31. Levels of ROS, MDA TNF-α and IL-6 decreased, while GSH increased in LQ treatment group, indicating a strong anti-oxidative and an- ti-inflammatory activity of LQ. The expression of antioxidant proteins Nff-2 and HO-1, tumor suppressors P53 and p-PTEN, and the MAPK pathways in tumor tissues were upregulated by LQ treatment. Conclusions LQ exhibited strong antitumor activity against B16-F10 murine melanoma both in vitro and in vivo. The antitumor effect of LQ in- volved the decreased oxidative stress and inflammation in tumor, which is closely related to the heat-clearing and detoxicating properties of LQ.
基金The project is supported by Pneumoconiosis Compensation Fund Board(6903114),HKSAR Government,Hong Kong
文摘OBJECTIVE To investigate the therapeutic effects and related signaling pathways involved in the actions of resveratrol on experimental pneumoconiosis in vivo and in vitro.METHODS The pneumoconiosis animal model was induced by exposing male SD rats to 15mg·m-3 silica aerosol in an inhalation chamber system for 6h·d-1,5d·week-1 for up to 8 weeks.The vehicle or resveratrol(10or 20mg·kg-1)was preventively or remedially administered to the rats during or after the 4-or 8-week silica exposure(SE)period,respectively.After 4-,8-,and up to 14-week treatment,in vivo near-infrared fluorescence imaging analysis and histological analysis were performed to evaluate the pathological changes in rat lung.Inflammatory cytokines level in bronchoalveolar lavage fluid(BALF)was measured by ELISA testing,and the deposition of fibrotic collagen proteins in lung parenchyma was determined by western blotting and immunohistochemistry analysis.Microarray analysis was performed to screen the signaling pathways involved in the actions of resveratrol on pneumoconiosis in vitro models.Anti-inflammation action and signaling of resveratrol was evaluated on silica-stimulated rat alveolar macrophage,which is one of the crucial effector cells for silica-induced inflammatory response;anti-fibrosis action and signaling of resveratrol was evaluated on TGF-β-induced human lung fibroblast,which acts as a promoter in the later fibrotic process of pneumoconiosis.RESULTS Silica aerosol exposure significantly increased macrophage infiltration and matrix metalloproteinases activity in lung tissue concomitant with the increased levels of inflammatory mediators in BALF.Preventive treatment with resveratrol(20mg·kg-1·d-1)reversed all these biochemical indices as well as histopathological alterations induced by silica exposure.Post-SE resveratrol treatment mildly reduced silica-induced inflammatory response in rat lung with no statistical significance.In vitro study revealed that resveratrol could inhibit alveolar macrophage cell death and decrease the levels of IL-1β and TNF-αinduced by silica particle exposure to cultured alveolar macrophages.Resveratrol was further shown to inhibit the nuclear transition of NF-κB and formation of cleaved caspase-1.Encouragingly,resveratrol preventively attenuated the lung fibrosis,evidenced by less fibrotic nodules formation and collagen proteins expression.No significant improvement on lung fibrosis was observed with post-SE resveratrol treatment.Invitrostudy further demonstrated that resveratrol suppressed TGF-β-induced lung fibroblast proliferation and collagen deposition,concomitant with the depressed activity of TGF-β/Smad signaling in lung fibroblast.CONCLUSION Resveratrol shows the anti-inflammation and anti-fibrosis actions on experimental pneumoconiosis in vivo and in vitro models.The depression of NF-κB,NALP3-inflammasome,and TGF-β/Smad signaling pathways may be involved in the anti-inflammation and anti-fibrosis actions of resveratrol,respectively.Resveratrol could be a potential therapeutic agent for the intervention of pneumoconiosis.
基金This work was financially supported by National Key R&D Project of China(No.2019YFC1708902,2019YFC1711000)National Natural Science Foundation(No.81973505,81773932).
文摘The ocean possesses a complex setting with high pressure,high salinity,oligotrophy,low temperature and weak illumination conditions.To survive and evolve in such harsh surroundings,marine organisms metabolize a series of chemicals known as secondary metabolites which indicate structural and functional diversity to adapt interspecific survival competition.During recent decades,the anti-inflammatory property of marine natural products has come under scrutiny as inflammation involves in the vast majority of diseases.Correspondingly,a myriad of marine bioactive molecules including terpenes,polypeptides,polysaccharides,sterols and many others may bring a new insight into inflammation therapies with multifarious sources and minimal side effects.And a better understanding of their mechanisms of anti-inflammation may lead to better treatments for numerous diseases.Herein,the research progress of marine-derived anti-inflammation compounds and the relevant mechanisms were reviewed,to provide a basis for the research and development of anti-inflammatory marine drugs.
文摘Parkinson’s disease（PD）is characterized by the progressive loss of midbrain dopaminergic（m DA）neurons and a subsequent decrease in striatal dopamine levels,which cause the typical clinical motor symptoms such as muscle rigidity,bradykinesia and tremor.
基金Funded by National Natural Science Foundation of China(82172076)Key Scientific Program of Jiangsu Provincial Health Commission(ZD2021033)+3 种基金Gusu Health Leading Talent Program of Suzhou(GSWS2021020)Discipline construction project of the Second Affiliated Hospital of Soochow University(XKTJXK202004)Scientific Program of Suzhou Municipal Health and Health Committee(LCZX202004)Project of Medical New Technology Assistance of the Second Affiliated Hospital of Soochow University(23ZL004 and 23ZL012).
文摘Cartilage tissue engineering offers hope for tracheal cartilage defect repair.Establishing an anti-inflammatory microenvironment stands as a prerequisite for successful tracheal cartilage restoration,especially in immunocompetent animals.Hence,scaffolds inducing an anti-inflammatory response before chondrogenesis are crucial for effectively addressing tracheal cartilage defects.Herein,we develop a shell–core structured PLGA@ICA-GT@KGN nanofilm using poly(lactic-co-glycolic acid)(PLGA)and icariin(ICA,an antiinflammatory drug)as the shell layer and gelatin(GT)and kartogenin(KGN,a chondrogenic factor)as the core via coaxial electrospinning technology.The resultant PLGA@ICA-GT@KGN nanofilm exhibited a characteristic fibrous structure and demonstrated high biocompatibility.Notably,it showcased sustained release characteristics,releasing ICA within the initial 0 to 15days and gradually releasing KGN between 11 and 29days.Subsequent in vitro analysis revealed the potent anti-inflammatory capabilities of the released ICA from the shell layer,while the KGN released from the core layer effectively induced chondrogenic differentiation of bone marrow stem cells(BMSCs).Following this,the synthesized PLGA@ICA-GT@KGN nanofilms were loaded with BMSCs and stacked layer by layer,adhering to a‘sandwich model’to form a composite sandwich construct.This construct was then utilized to repair circular tracheal defects in a rabbit model.The sequential release of ICA and KGN facilitated by the PLGA@ICA-GT@KGN nanofilm established an anti-inflammatory microenvironment before initiating chondrogenic induction,leading to effective tracheal cartilage restoration.This study underscores the significance of shell–core structured nanofilms in temporally regulating anti-inflammation and chondrogenesis.This approach offers a novel perspective for addressing tracheal cartilage defects,potentially revolutionizing their treatment methodologies.
基金the National Natural Science Foundation of China,Grant/Award Number:32000358the CAMS initiative for Innovative Medicine of China,Grant/Award Number:2021-I2M-1-035Young Elite Scientists Sponsorship Program by CAST(YESS),Grant/Award Number:2020QNRC001。
文摘Background:The aim was to elucidate the function of IL-37 in middle east respiratory syndrome coronavirus(MERS-CoV)infection,thereby providing a novel therapeutic strategy for managing the clinical treatment of inflammatory response caused by respiratory virus infection.Methods:We investigated the development of MERS by infecting hDPP4 mice with hCoV-EMC(107 TCID50[50%tissue culture infectious dose])intranasally.We infected A549 cells with MERS-CoV,which concurrently interfered with IL-37,detecting the viral titer,viral load,and cytokine expression at certain points postinfection.Meanwhile,we administered IL-37(12.5μg/kg)intravenously to hDPP4 mice 2 h after MERS-CoV-2 infection and collected the serum and lungs 5 days after infection to investigate the efficacy of IL-37 in MERS-CoV infection.Results:The viral titer of MERS-CoV-infected A549 cells interfering with IL-37 was significantly reduced by 4.7-fold,and the viral load of MERS-CoV-infected hDPP4 mice was decreased by 59-fold in lung tissue.Furthermore,the administration of IL-37 suppressed inflammatory cytokine and chemokine(monocyte chemoattractant protein 1,interferon-γ,and IL-17A)expression and ameliorated the infiltration of inflammatory cells in hDPP4 mice.Conclusion:IL-37 exhibits protective properties in severe pneumonia induced by MERS-CoV infection.This effect is achieved through attenuation of lung viral load,suppression of inflammatory cytokine secretion,reduction in inflammatory cell infiltration,and mitigation of pulmonary injury.
基金Supported by the Key Research and Development Plan Guidance Project of Heilongjiang Province(GZ20220039)Central Support for Local Universities Reform and Development Fund Talent Training Project(2020GSP16).
文摘In this paper,the anti-tumor,anti-inflammatory,antibacterial and anti-asthma effects of isobavachalcone and their molecular mechanisms were reviewed to provide theoretical support for further research of isobavachalcone and development of new drugs.
文摘Ten novel xanthones,garpedunxanthones A-G(1-5,6a/6b,7a/7b) and nujiangxanthone Q(8),along with sixteen known analogs(9-24),were isolated from Garcinia pedunculata and G.nujiangensis.Their structures were elucidated through high-resolution electrospray ionization mass spectrometry(HR-ESI-MS) data,comprehensive nuclear magnetic resonance(NMR) spectroscopic analyses,and electronic circular dichroism(ECD) calculations.All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide(NO) production in lipopolysaccharide(LPS)-induced RAW264.7cells.Structure-activity relationships are also discussed.Compounds 7b,19,and 21 exhibited significant anti-inflammatory activity with IC_(50) values of 16.44±0.69,14.28±0.78,and 10.67±3.28 μmol·L^(-1),respectively.Enzyme-linked immunosorbent assay(ELISA) demonstrated that compounds 7b,19,and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner.The inhibitory effect of compo und 21 on IL-6 at 20 μmol·L^(-1)was comparable to that of the positive control.In network pharmacology studies,potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation,including positive regulation of mitogen-activated protein kinase(MAPK) cascade,protein kinase activity,NO synthase regulator activity,MAPK signaling pathway,and EGFR tyrosine kinase inhibitor resistance.
基金the 4^(th) Brain Korea(BK)21 Plus Project(4299990913942)financed by the Korean Government,Republic of Korea.
文摘The inflammatory response is a crucial physiological process that can lead to tissue damage and is considered a causative factor for various chronic diseases,such as rheumatoid arthritis.Recent research has focused on exploring valuable nutrients derived from Cannabis sativa L.(hemp)seeds,particularly hemp seed proteins.Therefore,this study aimed to investigate the release of anti-inflammatory peptides from Lactobacillus paraplantarum-fermented hemp seed proteins.To confirm the complete hydrolysis of hemp seed proteins during the fermentation process,sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)was employed.Further,the isolation and purification of peptides were achieved through ultrafiltration.The identity of peptides was nextly established using ultra-high performance liquid chromatography coupled with hybrid quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS).The results revealed a total of 39 identified peptides in fermented hemp seeds,with 9 peptides selected based on their relative quantity.Notably,AAELIGVP(P1),AAVPYPQ(P2),VFPEVAP(P4),DVIGVPLG(P6),and PVPKVL(P9)demonstrated strong anti-inflammatory abilities in lipopolysaccharide(LPS)-induced RAW264.7 macrophage cells.Molecular docking was used to understand the potential anti-inflammatory mechanism of these 5 peptides,and in silico results indicated that P1,P2,P4,P6,and P9 could bind to the active sites of toll-like receptor 4(TLR-4),nuclear factor-κB(NF-κB),and inhibitor of NF-κB kinase(IKK)with higher binding energies.Overall,these findings indicate that hemp seeds have potential to be a source of bioactive peptides for functional foods with anti-inflammatory properties.
基金The National Natural Science Foundation of China(Grant No.82003770)the National Science and Technology Major Project of China(Grant No.2018ZX09711001-001-017)the Key Research and Development Plan of Shanxi Province(Grant No.202102130501005)。
文摘This study aimed to investigate the anti-inflammatory properties and underlying molecular mechanisms of 2,4',5'-trihydroxyl-5,2'-dibromo diphenylmethanone(LM49)using a carrageenan-induced paw edema model in mice,which serves as a well-established model for acute inflammation.Mice were randomly assigned into six groups,and acute inflammation was induced by injecting 1%carrageenan solution into the paw.To elucidate the anti-inflammatory effects and mechanisms of LM49,a comprehensive approach was employed,including pathology,transcriptomics,flow cytometry,RT-qPCR,Western blotting analysis,and molecular docking analysis.The results demonstrated that LM49 exerted a significant protective effect by reducing paw edema and lowering serum levels of pro-inflammatory cytokines IL-1βand TNF-a,while concurrently elevating anti-inflammatory cytokine IL-10 levels.Transcriptomic analysis identified 453 differentially expressed genes in the LM49-treated group.KEGG and GO enrichment analyses indicated that LM49 suppressed the NF-kB signaling pathway and modulated several other immuneinflammatory pathways.Molecular docking studies identified eight key targets of LM49 within the NF-kB signaling pathway.Furthermore,Western blotting analysis confirmed that LM49 inhibited the phosphorylation of p65 and IB-αand downregulated the expression of MYD88 and TLR4 in mouse paw tissues.These findings provided a foundational understanding of the anti-inflammatory effects and molecular mechanisms of LM49,paving the way for further in-depth studies in this field.
基金supported by the National Natural Science Foundation of China(Grant No.52272276,52073103,52203164)the Key-Area Research and Development Program of Guangdong Province(Grant No.2020B090924004)+2 种基金the funds for Zhongshan Innovation Project of high-end Scientific Research Institutions(Grant No.2020AG020)the Fundamental Research Funds for the Central Universities(No.2022ZYGXZR105)Guangdong Basic and Applied Basic Research Foundation(Grant No.2021A1515010905).
文摘Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer.At present,most of wound repair materials are passive and can’t response to the wound microenvironment,resulting in a low utilization of bioactive substances and hence a poor therapeutic effect.Therefore,it’s essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality.In this work,metformin-laden CuPDA NPs composite hydrogel(Met@CuPDA NPs/HG)was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine(Gel-DA),Cu-loaded polydopamine nanoparticles(CuPDA NPs)with hyaluronic acid modified by phenyl boronate acid(HA-PBA),which possessed good injectability,self-healing,adhesive and DPPH scavenging performance.The slow release of metformin was achieved by the interaction with CuPDA NPs,boric groups(B-N coordination)and the constraint of hydrogel network.Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently.Moreover,CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of>95%within 10 min and also the slow release of Cu^(2+)to protect wound from infection for a long time.Met@CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu^(2+).More importantly,Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway.Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria,inhibiting inflammation,improving angiogenesis and accelerating the deposition of ECM and collagen.Therefore,Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.
基金National Natural Science Foundation of China Granted Project(81273903)
文摘Objective To investigate the inhibitory effect of Tripterygium wilfordii polycoride（TWP） towards the pro-inflammatory factors（TNF-α and IL-1β） on the inflammatory reaction in macrophages induced by LPS and its regulatory effect and influence on the inflammation via TLR4/NF-k B. Methods The MTT method was adopted to test the effect of drugs, TWP, dexamethasone（DXM） and azathioprine（AZA） on cell growth and to select the appropriate concentration. LPS was used to induce the inflammatory reaction in RAW264.7 cell line of mice. Elisa kit was adopted to test the levels of TNF-α and IL-1β. Western blotting was adopted to test the protein expression of TNF-α and IL-1β. RT-PCR was adopted to test the expression of TLR4 and NF-κB. Results The inhibiting effect of TWP on the release of TNF-α and IL-1β in a dose dependent manner. The inhibitory effect of three different TWP dose groups is weaker than that in DXM group. However, TWP in high dose is better than AZA on TNF-α and is as strong as AZA on IL-1β. The dose dependent manner also exits in the effect on the expression of TLR4 and NF-κB, the effect is not weaker, but even stronger than that of DXM and AZA. Conclusion The research shows that down regulation of TLR4 and NF-k B p65 may be one of the mechanisms about the TWP inhibitory effect on TNF-α and IL-1β.
基金supported by the National Natural Science Foundation of China,Nos.82072051 and 81771964(both to JG)the Natural Science Foundation of Shanghai Municipal Science and Technology Commission,No.22ZR147750(to YY)+2 种基金Science and Technology Support Projects in Biomedicine Field of Shanghai Science and Technology Commission,No.19441907500(to YY)Innovative Clinical Research Project of Changzheng Hospital,No.2020 YLCYJ-Y02(to YY)Characteristic Medical Service Project for the Army of Changzheng Hospital,No.2020 CZWJFW12(to YY)。
文摘The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.
基金supported by the National Natural Science Foundation of China(No.81973449).
文摘The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and diversity.Previous studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket of protein kinase B(AKT),and swertiamarin(Swe)acts on the pleckstrin homology(PH)domain of AKT.However,the combined synergistic effect of relieving the inflammatory response has yet to be elucidated.Based on high sensitivity,specificity and fast-responsibility fluorescent sensors,the Förster resonance energy transfer(FRET)technique offers a route to provide clear insights into physiological and pathological processes.In the study,molecular docking,the fluorescent probes of Phi and Swe for FRET were designed and synthesized.FRET analysis shown that Swe and Phi concurrently acted on the PH domain and allosterically inhibited pocket of AKT,respectively.The combination of Swe and Phi significantly increased the heat stability of AKT and decreased protease-induced degeneration.In lipopolysaccharides(LPS)-induced mice and cells,the combination arrested AKT activation,nuclear factor kappa-B(NF-κB)phosphorylation,and the expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8.In conclusion,FRET revealed Phi and Swe concurrently targeted AKT on different domains and the combination of Phi and Swe enhanced the anti-inflammatory effect.
