BACKGROUND Malignant meningioma metastasizes systemically,primarily due to its role in epithelial-mesenchymal transition.Although the prognosis is extremely poor,drug development efforts have been limited,because this...BACKGROUND Malignant meningioma metastasizes systemically,primarily due to its role in epithelial-mesenchymal transition.Although the prognosis is extremely poor,drug development efforts have been limited,because this tumor is categorized as a rare form.AIM To examine growth suppressive effect of GO-Y030,a diarylpentanoid curcumin analog,(1E,4E)-1,5-bis[3,5-bis(methoxymethoxy)phenyl]penta-1,4-dien-3-one against the malignant meningioma.METHODS The growth suppression of malignant meningioma cells by GO-Y022 and GOY030 were examined,using IOMM-Lee and HKBMM cell lines.Male nude mice aged eight weeks,specifically BALB/cSlc-nu/nu mice received a subcutaneous inoculation of IOMM-Lee(107 cells/site)on their back and 30μg/kg of recombinant hepatocellular growth factor(HGF)was injected into the tumor every three days.After confirmed the growth tumor mass,500μL of GO-Y030 diluted with PBS were administrated intraperitoneally daily at doses of 1 mg/kg and 2 mg/kg,respectively.RESULTS GO-Y030 exhibits a growth inhibitory effect on malignant meningioma cell lines,IOMM-Lee and HKBMM ranging from 0.8-2.0μM in vitro.Notably,GO-Y030’s inhibitory effect is about 10 to 16th times more potent than that of curcumin,which has previously demonstrated potential in combating malignant meningioma.In mouse models,the intraperitoneal administration of GO-Y030 effectively suppresses the growth of malignant meningioma tumors that have been inoculated in the back(P=0.002).High-performance liquid chromatography analysis has confirmed the distribution of GO-Y030 in the bloodstream and brain tissue.Moreover,GOY030 demonstrates the ability to significantly suppress HGF(P<0.01),nuclear factor kappa B(P<0.001),and Ncadherin(P<0.001),all of which contribute to the epithelial-mesenchymal transition.CONCLUSION GO-Y030 holds promise as a potent compound for the systemic inhibition of malignant meningioma.GO-Y030 has higher tumor growth inhibitory effect against meningiomas than curcumin,which is known to have antitumor activity through multi-molecular target control resulting in apoptosis induction.GO-Y030 controls at least three molecules of HGF,nuclear factor kappa B,and N-cadherin.展开更多
The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of ...The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC targets.Key genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC patients.Molecular docking con-firmed strong binding affinity of curcumin to these genes.In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.展开更多
Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM...Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM)to induce hepatotoxicity,followed by treatment with turmeric extract and its isolated compounds including curcumin,demethoxycurcumin,bis-demethoxycurcumin and ar-turmerone at 5,25,and 125μg/mL.IL-1β,IL-6,and IL-10 levels were quantified with ELISA kits.Further,qRT-PCR was used to analyze the mRNA expression of JNK,Casp-9,and Casp-3.Meanwhile,the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.Results:Acetaminophen administration caused an increase in the levels of lactate dehydrogenase,nitric oxide,IL-1β,IL-6,and the mRNA expression of JNK,Casp-9,and Casp-3 in HepG2 cells while reducing IL-10 levels.Treatment with turmeric extract,curcumin,demethoxycurcumin,bis-demethoxycurcumin,and ar-turmerone lowered IL-1β,IL-6,nitric oxide,and lactate dehydrogenase levels,downregulated the mRNA expression of JNK,Casp-9,and Casp-3,and increased IL-10 levels.Conclusions:Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.展开更多
Micellar nanostructures formed by amphiphilic polymers are prone to dissociation when the in vivo environment changes.Polyprodrug micelles can cross-link with other hydrophobic drugs through noncovalent bonds,which ha...Micellar nanostructures formed by amphiphilic polymers are prone to dissociation when the in vivo environment changes.Polyprodrug micelles can cross-link with other hydrophobic drugs through noncovalent bonds,which has the advantage of fixed structure and avoids the use of chemical cross-linking agents.In this study,we prepared a polyprodrug with hydrophobic curcumin(CUR)and hydrophilic poly(ethylene glycol)(PEG)in the main chain through a click reaction between CUR derivatives containing azide groups and di-alkynly-capped PEG.Due to the presence of benzene rings in the structure of CUR,the polyprodrug can form non-covalent cross-linked nanoparticles(NCCL-CUR NPs)through hydrophobic andπ-πstacking interaction.The structure,molecular weight,and self-assembly properties of the polyprodrug were characterized.The anti-cancer drug camptothecin(CPT)was encapsulated in the polyprodrug nanoparticles,producing dual-drug-loaded nanoparticles(abbreviated as CPT@NCCL-CUR NPs).The test results indicate that the NPs have reductive responsiveness and can release the original drugs CUR and CPT in phosphate buffer(PB)solution containing glutathione(GSH),while remaining stability in physiological environment.Cell and in vivo experiments further demonstrate that the dualdrug-loaded CPT@NCCL-CUR NPs can inhibit the growth of tumor through synergistic effects.This work provides a valuable approach for the preparation of amphiphilic polyprodrug with anti-tumor CUR as the backbone,and the stable dual-drug-loaded NPs containing both CUR and CPT through non-covalent cross-linking for synergistic therapy.展开更多
We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepa...We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepared(by CM-β-CD and chitosan)and consequently characterized by DLS,TEM,FT-IR,~1H NMR,SEM,etc.In vitro release results show that Cur-loaded Chitosan-CM-β-CD nanogel(Cur-CS-CM-β-CD)released Cur rapidly under acidic conditions,and its cumulative release rate is 41%,56%and 67%at pH 7.4,6.5 and 5.5,respectively.The cell inhibition rate of Cur-CS-CM-β-CD on MCF-7 cell lines was detected by the MTT assay.The results suggest the cell inhibition rate of Cur-CS-CM-β-CD is(50.2±2.5)%at 10μM,(98.3±1.2)%at 40μM and(97.5±1.2)%at 80μM,respectively.It is revealed that the pH-responsive nanogel loaded Cur can effectively inhibit the growth of breast cancer cells and has the potential for clinical application.展开更多
The prevalence of ulcerative colitis(UC)is increasing annually,while current non-targeted drugs for UC have limited effectiveness,easily relapsed,and serious side effects.Herein,curcumin(Cur)-loaded nanoparticle with ...The prevalence of ulcerative colitis(UC)is increasing annually,while current non-targeted drugs for UC have limited effectiveness,easily relapsed,and serious side effects.Herein,curcumin(Cur)-loaded nanoparticle with conlon-targeted property based on Mesona chinensis polysaccharides(MCP)was developed for the synergistic and targeted improvement of UC.Results show that MCP-zein nanoparticles(ZmNPs)have good encapsulation of Cur,targeted delivery of Cur to the colon,and prolonged its retention time.In vivo safety assessments have shown that ZmNPs have good safety and biocompatibility.As expected,Cur-ZmNPs effectively alleviated the symptoms of Dextran sulfate sodium(DSS)-induced UC by decreasing colonic inflammation by inhibiting the TLR4/MAPK pathway,regulating the levels of oxidative stress and immune homeostasis of UC mice.Oral administration of Cur-ZmNPs can reduce apoptosis of intestinal epithelial cells,alleviate colonic mucosal damage and repair intestinal barrier function.Cur-ZmNPs also had a positive effect on improving gut microbiota disorders and promoting the production of SCFAs.This study provides a novel strategy for synergistic alleviation of UC by MCP-based NPs loaded with food bioactives.展开更多
The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curc...The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curcumin,a polyphenolic compound derived from turmeric,exhibits diverse pharmacological properties,including anti-inflammatory,antioxidant,and anticancer effects.Understanding how curcumin modulates gut microbiota composition and function is crucial for elucidating its therapeutic mechanisms.This review examines the current literature on the interactions between curcumin and the gut microbiome.A systematic search of relevant databases was conducted to identify studies investigating the effects of curcumin on gut microbial diversity and abundance.Key findings from studies exploring curcumin's efficacy in neurological disorders,gastrointestinal diseases,and metabolic dysfunction are synthesized and discussed.Studies have demonstrated that curcumin supplementation can modulate gut microbiota composition and function,leading to beneficial effects on gut health and homeostasis.Mechanisms underlying curcumin's therapeutic effects include immune modulation,neuroprotection,and inflammation regulation.However,challenges such as poor bioavailability and safety concerns remain significant hurdles to overcome.The interactions between curcumin and the gut microbiome hold promise for therapeutic interventions in a diverse range of health conditions.Further research is needed to optimize curcumin formulations,improve bioavailability,and address safety concerns.展开更多
Objective:To observed the effect of a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis(VVC)caused by Candida albicans.Methods:Temperature-sensitive in situ gels(IS...Objective:To observed the effect of a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis(VVC)caused by Candida albicans.Methods:Temperature-sensitive in situ gels(ISG)were prepared using poloxamers 407 and 188 as matrices.The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29℃ and gelation time of 2.5 min.Results:Electroporation increased the transmucosal permeability of the model drug,doxorubicin and improved the antifungal effects of curcumin.In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG.In vivo pharmacodynamic experiments showed that,compared to the model group,curcumin ISG with electroporation inhibited the growth of C.albicans,alleviated vaginal mucosal edema,and reduced the inflammatory response.Conclusion:Curcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.展开更多
Acute lung injury(ALI)is a critical respiratory disorder with a high mortality rate and is caused by several factors.Addressing oxidative stress and infiammation is a pivotal strategy for ALI treatment.In this study,w...Acute lung injury(ALI)is a critical respiratory disorder with a high mortality rate and is caused by several factors.Addressing oxidative stress and infiammation is a pivotal strategy for ALI treatment.In this study,we introduced a novel nanotherapeutic approach involving a curcumin-loaded ceria nanoenzyme delivery system tailored to counteract the multifaceted aspects of ALI.This system leverages the individual and combined effects of the components to provide a comprehensive therapeutic solution.The dual-action capability of this nanosystem was manifested by mitigating mitochondrial oxidative stress in lung epithelial cells and inhibiting the transient receptor potential melanosome-associated protein 2(TRPM2)-NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway,offering a highly effective therapeutic approach to ALI.Our findings reveal the underlying mechanisms of this innovative nanodelivery system,showcasing its potential as a versatile strategy for ALI treatment and encouraging further exploration of nanoenzyme-based therapies for ALI.展开更多
Soil salinization is a major abiotic stress that hampers plant development and significantly reduces agricultural productivity,posing a serious challenge to global food security.Akebia trifoliata(Thunb.)Koidz,a specie...Soil salinization is a major abiotic stress that hampers plant development and significantly reduces agricultural productivity,posing a serious challenge to global food security.Akebia trifoliata(Thunb.)Koidz,a species within the genus Akebia Decne.,is valued for its use in food,traditionalmedicine,oil production,and as an ornamental plant.Curcumin,widely recognized for its pharmacological properties including anti-cancer,anti-neuroinflammatory,and anti-fibrotic effects,has recently drawn interest for its potential roles in plant stress responses.However,its impact on plant tolerance to saline-alkali stress remains poorly understood.In this study,the effects of curcumin on saline-alkali resistance in A.trifoliata were examined by subjecting plants to a saline-alkali solution containing 150 mmol/L sodium ions(a mixture of Na_(2)SO_(4),Na_(2)CO_(3),and NaHCO_(3)).Curcumin treatment under these stress conditions leads to anatomical improvements in leaf structure.Furthermore,A.trifoliatamaintained a favorable Na^(+)/K^(+)ratio through increased potassium uptake and reduced sodium accumulation.Biochemical analysis revealed elevated levels of proline,soluble sugars,and soluble proteins,along with improved activities of antioxidant enzymes such as superoxide dismutase(SOD),catalase(CAT),and peroxidase(POD).Similarly,the concentrations of hydrogen peroxide(H_(2)O_(2))and malondialdehyde(MDA)were significantly reduced.Transcriptome analysis under saline-alkali stress conditions showed that curcumin influenced seven keymetabolic pathways annotated in the Kyoto Encyclopedia of Genes and Genomes(KEGG)database,with differentially expressed unigenes primarily enriched in transcription factor families such as MYB,AP2/ERF,NAC,bHLH,and C2C2.Moreover,eight differentially expressed genes(DEGs)associated with plant hormone signal transduction were linked to the auxin and brassinosteroid pathways,critical for cell elongation and plant growth.These findings indicate that curcumin increases saline-alkali stress tolerance in A.trifoliata by modulating physiological,biochemical,and transcriptional responses,ultimately supporting improved growth under adverse conditions.展开更多
Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug d...Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug delivery.In this study,we proposed a time-efficient method,PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles(GDNVs).Subsequently,curcumin(CUR)was loaded onto GDNV by ultrasonic incubation.The optimum conditions for ginger-derived nanovesicles loaded with curcumin(CG)were ultrasound time of 3 min,a carrier-to-drug ratio(GDNV:CUR)of 1:1.The study achieved a high loading capacity(94.027%±0.094%)and encapsulation efficiency(89.300%±0.344%).Finally,the drugs'in vivo distribution and anti-colitis activity were investigated in mice.CG was primarily distributed in the colon after oral administration.Compared to CUR and GDNV,CG was superior in improving disease activity,colon length,liver and spleen coefficients,myeloperoxidase activity,and biochemical factor levels in ulcerative colitis(UC)mice.In addition,CG plays a protective role against UC by modulating serum metabolite levels and gut flora.In summary,our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.展开更多
The growth rate method was adopted to measure the inhibitory effect of curcumin,tetrahydrocurcumin,demethoxycurcumin,and bisdemethoxycurcumin on the mycelial growth of Botrytis cinerea and Colletotrichum gloeosporioid...The growth rate method was adopted to measure the inhibitory effect of curcumin,tetrahydrocurcumin,demethoxycurcumin,and bisdemethoxycurcumin on the mycelial growth of Botrytis cinerea and Colletotrichum gloeosporioides.The results showed that the four curcuminoids inhibited the mycelial growth of the two pathogens in a concentration-dependent manner.Bisdemethoxycurcumin at 600 mg/L exerted the strongest inhibitory effect on the mycelial growth of B.cinerea and C.gloeosporioides,with the relative inhibition rates of 98.19%and 100%,respectively;followed by demethoxycurcumin;curcumin exerted the worst inhibitory effect.Toxicity test results also showed that four curcuminoids all had a certain toxicity to B.cinerea and C.gloeosporioides,among which,bisdemethoxycurcumin exhibited the strongest toxicity,with the EC_(50)of 131.125 and 122.235 mg/L,respectively;while curcumin had the lowest toxicity,with the EC_(50)of 273.143 and 194.943 mg/L,respectively.展开更多
Background:Breast cancer(BC)continues to be a significant global health issue,with a rising number of cases requiring ongoing research and innovation in treatment strategies.Curcumin(CUR),a natural compound derived fr...Background:Breast cancer(BC)continues to be a significant global health issue,with a rising number of cases requiring ongoing research and innovation in treatment strategies.Curcumin(CUR),a natural compound derived from Curcuma longa,and similar compounds have shown potential in targeting the STAT3 signaling pathway,which plays a crucial role in BC progression.Aims:The aim of this study was to investigate the effects of curcumin and its analogues on BC based on cellular and molecular mechanisms.Materials&Methods:The literature search conducted for this study involved utilizing the Scopus,ScienceDirect,PubMed,and Google Scholar databases in order to identify pertinent articles.Results:This narrative review explores the potential of CUR and similar compounds in inhibiting STAT3 activation,thereby suppressing the proliferation of cancer cells,inducing apoptosis,and inhibiting metastasis.The review demonstrates that CUR directly inhibits the phosphorylation of STAT3,preventing its movement into the nucleus and its ability to bind to DNA,thereby hindering the survival and proliferation of cancer cells.CUR also enhances the effectiveness of other therapeutic agents and modulates the tumor microenvironment by affecting tumor-associated macrophages(TAMs).CUR analogues,such as hydrazinocurcumin(HC),FLLL11,FLLL12,and GOY030,show improved bioavailability and potency in inhibiting STAT3,resulting in reduced cell proliferation and increased apoptosis.Conclusion:CUR and its analogues hold promise as effective adjuvant treatments for BC by targeting the STAT3 signaling pathway.These compounds provide new insights into the mechanisms of action of CUR and its potential to enhance the effectiveness of BC therapies.展开更多
Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes...Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.展开更多
BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promi...BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promise in gastric cancer.Its effects include promoting cell apoptosis,curtailing tumor angiogenesis,and enhancing sensitivity to radiation and chemotherapy.Long noncoding RNAs(lncRNAs)have garnered significant attention as biomarkers for early screening,diagnosis,treatment,and drug response because of their remarkable specificity and sensitivity.Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis,clinical staging,metastasis,drug sensitivity,and prognosis in gastric cancer.A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer develop-ment can provide novel insights for precision treatment and tailored management of patients with gastric cancer.This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregu-lating specific lncRNAs and modulating gastric cancer onset and progression.AIM To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis,proliferation,and invasion.Furthermore,these findings were validated in clinical samples.METHODS The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation,flow cytometry to investigate its effects on apoptosis,and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells.Western blotting was used to gauge changes in the protein expression levels of CDK6,CDK4,Bax,Bcl-2,caspase-3,P65,and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment.Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction(qRT-PCR)in BGC-823 and MGC-803 cells.AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis,proliferation,migration,and invasion of gastric cancer cells.Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways.RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics.RESULTS Curcumin induced apoptosis and hindered proliferation,migration,and invasion of gastric cancer cells in a dose-and time-dependent manner.LncRNA AC022424.2 was upregulated after curcumin treatment,and its knockdown enhanced cancer cell aggressiveness.LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways.LncRNA AC022424.2 downregulation was correlated with lymph node metastasis,making it a potential diagnostic and prognostic marker.CONCLUSION Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2.This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation.The results of this study enhance our understanding of gastric cancer development and precision treatment.展开更多
The microphases and miscibility in binary curcumin(Cur)solid dispersions(SDs)with amorphous polyvinylpyrrolidone K30(PVP K30)and semi-crystalline poloxamer(P407)and poly(ethylene glycol)6000(PEG6000)as carriers were i...The microphases and miscibility in binary curcumin(Cur)solid dispersions(SDs)with amorphous polyvinylpyrrolidone K30(PVP K30)and semi-crystalline poloxamer(P407)and poly(ethylene glycol)6000(PEG6000)as carriers were investigated by fluorescence contrasting utilizing confocal laser scanning microscopy.A super sensitive fluorophore P4 with typical aggregation-caused quenching properties was employed to stain the continuous polymer phases and contrasted with the autofluorescence of the model drug Cur.In addition,differential scanning calorimetry(DSC)and powder X-ray diffraction(PXRD)were utilized to assist in explanation of the fluorescence results.In all three SD systems,there is always a homogenous polymer phase stained by P4 and it is difficult to adulterate Cur crystals by P4.Cur-enriched rather than polymer-enriched domains could be detected.In the Cur-PVP K30 system,Cur exists in an amorphous form at a Cur loading level of 50%and below,while Cur crystallines phase out and continuously grow with the increase of Cur loading from 60%to 90%.The phase behaviors in the Cur-P407 and Cur-PEG 6000 systems are similar but with minor differences.In both systems,Cur phases out as clusters of drug-enriched domains at a loading level of 20%and below,which however cannot be correlated with crystallization,as evidenced by both DSC and PXRD.There is a transition from an amorphous to a crystalline state from 20%to 30%Cur loading,above which Cur crystallines can be detected.It is interesting that a co-mix phase of both Cur-and PEG 6000-enriched domains can be identified at Cur loading levels of 10%and less.Taking together,it is concluded that contrasting Cur autofluorescence with the signals of P4 proves to be a functional strategy to reveal multiple phases in the binary SD systems investigated.展开更多
Inflammatory bowel disease(IBD)is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis.Because IBD is difficult to heal and easily relapses,it could worsen patient ...Inflammatory bowel disease(IBD)is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis.Because IBD is difficult to heal and easily relapses,it could worsen patient quality of life and increase economic burdens.Curcumin(CUR)is a bioactive component derived from the rhizome of turmeric(Curcuma longa).Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules.However,due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability,it is important to select appropriate pharmaceutical preparations.展开更多
BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.A...BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.展开更多
Curcumin is a natural polyphenol that is used in various traditional medicines.However,its inherent properties,such as its rapid degradation and metabolism,low bioavailability,and short half-life,are serious problems ...Curcumin is a natural polyphenol that is used in various traditional medicines.However,its inherent properties,such as its rapid degradation and metabolism,low bioavailability,and short half-life,are serious problems that must be resolved.To this end,a drug carrier incorporating natural magnetic cores in a zeolite framework was developed and applied to the loading of curcumin in ethanol solutions.In this system,curcumin is encapsulated in a zeolite Na(ZNA)magnetic core–shell structure(Fe@Si/ZNA),which can be easily synthesized using an in situ method.Synthesis of Fe_(3)O_(4) nanoparticles was carried out from natural materials using a co-precipitation method.Analysis of the prepared magnetic core–shell structures and composites was carried out using vibrating-sample magnetometery,Fourier transform infrared spectroscopy,transmission electron microscopy,and x-ray diffraction.The cumulative loading of curcumin in the ZNA composite with 9%nanoparticles was found to reach 90.70%with a relatively long half-life of 32.49 min.Stability tests of curcumin loading in the composite showed that adding magnetic particles to the zeolite framework also increased the stability of the composite structure.Adsorption kinetics and isotherm studies also found that the system follows the pseudo-second-order and Langmuir isotherm models.展开更多
The aim of this study is to investigate the feasibility of Maillard reaction products of Haematococcus pluvialis protein and galactose(HPP-GAL)for improving the bioactivities of curcumin(CUR)for alleviating alcoholic ...The aim of this study is to investigate the feasibility of Maillard reaction products of Haematococcus pluvialis protein and galactose(HPP-GAL)for improving the bioactivities of curcumin(CUR)for alleviating alcoholic liver damage.CUR was embedded into HPP-GAL nanoparticles by the self-assembly of hydrogen bonding and hydrophobic interaction with the particle size around 200 nm.HPP-GAL enhanced the encapsulation efficiency and loading amount of CUR with the value of(89.21±0.33)%and(0.500±0.004)%,respectively.The stabilities of CUR under strong acid,salt ion stability and ultraviolet irradiation conditions were improved by the encapsulation.HPP-GAL-CUR nanoparticles exhibited excellent concentration-dependent in vitro antioxidant activities including DPPH and ABTS scavenging rates,and better protective effect on CUR against gastric acid environment as well as longer release of CUR in simulated intestinal fluid.In addition,the HPPGAL-CUR delivery system possessed liver targeting property due to the existence of GAL,which could effectively alleviate the alcohol-induced liver damage and the inflammation indexes by inhibiting the oxidative stress.Therefore,HPP-GAL-CUR nanoparticles might be a potential candidate system for the prevention of alcoholic liver damage in the future.展开更多
基金Supported by TAIHO Pharmaceutical,No.AS2023A000122715Nippon Kayaku,No.NKCS20230416001.
文摘BACKGROUND Malignant meningioma metastasizes systemically,primarily due to its role in epithelial-mesenchymal transition.Although the prognosis is extremely poor,drug development efforts have been limited,because this tumor is categorized as a rare form.AIM To examine growth suppressive effect of GO-Y030,a diarylpentanoid curcumin analog,(1E,4E)-1,5-bis[3,5-bis(methoxymethoxy)phenyl]penta-1,4-dien-3-one against the malignant meningioma.METHODS The growth suppression of malignant meningioma cells by GO-Y022 and GOY030 were examined,using IOMM-Lee and HKBMM cell lines.Male nude mice aged eight weeks,specifically BALB/cSlc-nu/nu mice received a subcutaneous inoculation of IOMM-Lee(107 cells/site)on their back and 30μg/kg of recombinant hepatocellular growth factor(HGF)was injected into the tumor every three days.After confirmed the growth tumor mass,500μL of GO-Y030 diluted with PBS were administrated intraperitoneally daily at doses of 1 mg/kg and 2 mg/kg,respectively.RESULTS GO-Y030 exhibits a growth inhibitory effect on malignant meningioma cell lines,IOMM-Lee and HKBMM ranging from 0.8-2.0μM in vitro.Notably,GO-Y030’s inhibitory effect is about 10 to 16th times more potent than that of curcumin,which has previously demonstrated potential in combating malignant meningioma.In mouse models,the intraperitoneal administration of GO-Y030 effectively suppresses the growth of malignant meningioma tumors that have been inoculated in the back(P=0.002).High-performance liquid chromatography analysis has confirmed the distribution of GO-Y030 in the bloodstream and brain tissue.Moreover,GOY030 demonstrates the ability to significantly suppress HGF(P<0.01),nuclear factor kappa B(P<0.001),and Ncadherin(P<0.001),all of which contribute to the epithelial-mesenchymal transition.CONCLUSION GO-Y030 holds promise as a potent compound for the systemic inhibition of malignant meningioma.GO-Y030 has higher tumor growth inhibitory effect against meningiomas than curcumin,which is known to have antitumor activity through multi-molecular target control resulting in apoptosis induction.GO-Y030 controls at least three molecules of HGF,nuclear factor kappa B,and N-cadherin.
基金Supported by The College Students’Innovation and Entrepreneurship Competition,No.2024cxcy504 and No.202410459164.
文摘The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC targets.Key genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC patients.Molecular docking con-firmed strong binding affinity of curcumin to these genes.In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.
基金funded by Maranatha Christian University,Bandung,Indonesia for Productive Lecturer Research under grant number:011/SK/ADD/UKM/IV/2024.
文摘Objective:To assess the effects of turmeric extract and its compounds on oxidative stress,inflammation,and apoptosis in acetaminophen-induced liver injury.Methods:HepG2 cells were administered with acetaminophen(40 mM)to induce hepatotoxicity,followed by treatment with turmeric extract and its isolated compounds including curcumin,demethoxycurcumin,bis-demethoxycurcumin and ar-turmerone at 5,25,and 125μg/mL.IL-1β,IL-6,and IL-10 levels were quantified with ELISA kits.Further,qRT-PCR was used to analyze the mRNA expression of JNK,Casp-9,and Casp-3.Meanwhile,the levels of nitric oxide and lactate dehydrogenase were analyzed using colorimetric assay.Results:Acetaminophen administration caused an increase in the levels of lactate dehydrogenase,nitric oxide,IL-1β,IL-6,and the mRNA expression of JNK,Casp-9,and Casp-3 in HepG2 cells while reducing IL-10 levels.Treatment with turmeric extract,curcumin,demethoxycurcumin,bis-demethoxycurcumin,and ar-turmerone lowered IL-1β,IL-6,nitric oxide,and lactate dehydrogenase levels,downregulated the mRNA expression of JNK,Casp-9,and Casp-3,and increased IL-10 levels.Conclusions:Turmeric extract and its compounds have significant hepatoprotective activity and could be further explored for the treatment of liver damage.
基金supported by the National Natural Science Foundation of China(No.21975169)the Project Fund of the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions+2 种基金the Key Laboratory of Polymeric Materials Design and Synthesis for Biomedical Function of Soochow Universitythe Research project of China Baoyuan Investment Co.,Ltd.Suzhou Science and Technology Plan Project(No.SKY2023051)。
文摘Micellar nanostructures formed by amphiphilic polymers are prone to dissociation when the in vivo environment changes.Polyprodrug micelles can cross-link with other hydrophobic drugs through noncovalent bonds,which has the advantage of fixed structure and avoids the use of chemical cross-linking agents.In this study,we prepared a polyprodrug with hydrophobic curcumin(CUR)and hydrophilic poly(ethylene glycol)(PEG)in the main chain through a click reaction between CUR derivatives containing azide groups and di-alkynly-capped PEG.Due to the presence of benzene rings in the structure of CUR,the polyprodrug can form non-covalent cross-linked nanoparticles(NCCL-CUR NPs)through hydrophobic andπ-πstacking interaction.The structure,molecular weight,and self-assembly properties of the polyprodrug were characterized.The anti-cancer drug camptothecin(CPT)was encapsulated in the polyprodrug nanoparticles,producing dual-drug-loaded nanoparticles(abbreviated as CPT@NCCL-CUR NPs).The test results indicate that the NPs have reductive responsiveness and can release the original drugs CUR and CPT in phosphate buffer(PB)solution containing glutathione(GSH),while remaining stability in physiological environment.Cell and in vivo experiments further demonstrate that the dualdrug-loaded CPT@NCCL-CUR NPs can inhibit the growth of tumor through synergistic effects.This work provides a valuable approach for the preparation of amphiphilic polyprodrug with anti-tumor CUR as the backbone,and the stable dual-drug-loaded NPs containing both CUR and CPT through non-covalent cross-linking for synergistic therapy.
基金Funded by the Tianjin Municipal Education Commission(No.2022ZD041)。
文摘We prepared curcumin(Cur)/carboxymethyl-β-cyclodextrin(CM-β-CD)complex by grinding method.According to the characteristics of the tumor microenvironment,a pH-responsive nanogel loaded with Cur was designed and prepared(by CM-β-CD and chitosan)and consequently characterized by DLS,TEM,FT-IR,~1H NMR,SEM,etc.In vitro release results show that Cur-loaded Chitosan-CM-β-CD nanogel(Cur-CS-CM-β-CD)released Cur rapidly under acidic conditions,and its cumulative release rate is 41%,56%and 67%at pH 7.4,6.5 and 5.5,respectively.The cell inhibition rate of Cur-CS-CM-β-CD on MCF-7 cell lines was detected by the MTT assay.The results suggest the cell inhibition rate of Cur-CS-CM-β-CD is(50.2±2.5)%at 10μM,(98.3±1.2)%at 40μM and(97.5±1.2)%at 80μM,respectively.It is revealed that the pH-responsive nanogel loaded Cur can effectively inhibit the growth of breast cancer cells and has the potential for clinical application.
基金supported by the National Key Research and Development Program of China(2023YFF1104001)Natural Science Foundation of Jiangxi Province,China(20232BCD44003).
文摘The prevalence of ulcerative colitis(UC)is increasing annually,while current non-targeted drugs for UC have limited effectiveness,easily relapsed,and serious side effects.Herein,curcumin(Cur)-loaded nanoparticle with conlon-targeted property based on Mesona chinensis polysaccharides(MCP)was developed for the synergistic and targeted improvement of UC.Results show that MCP-zein nanoparticles(ZmNPs)have good encapsulation of Cur,targeted delivery of Cur to the colon,and prolonged its retention time.In vivo safety assessments have shown that ZmNPs have good safety and biocompatibility.As expected,Cur-ZmNPs effectively alleviated the symptoms of Dextran sulfate sodium(DSS)-induced UC by decreasing colonic inflammation by inhibiting the TLR4/MAPK pathway,regulating the levels of oxidative stress and immune homeostasis of UC mice.Oral administration of Cur-ZmNPs can reduce apoptosis of intestinal epithelial cells,alleviate colonic mucosal damage and repair intestinal barrier function.Cur-ZmNPs also had a positive effect on improving gut microbiota disorders and promoting the production of SCFAs.This study provides a novel strategy for synergistic alleviation of UC by MCP-based NPs loaded with food bioactives.
文摘The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions.Curcumin,a polyphenolic compound derived from turmeric,exhibits diverse pharmacological properties,including anti-inflammatory,antioxidant,and anticancer effects.Understanding how curcumin modulates gut microbiota composition and function is crucial for elucidating its therapeutic mechanisms.This review examines the current literature on the interactions between curcumin and the gut microbiome.A systematic search of relevant databases was conducted to identify studies investigating the effects of curcumin on gut microbial diversity and abundance.Key findings from studies exploring curcumin's efficacy in neurological disorders,gastrointestinal diseases,and metabolic dysfunction are synthesized and discussed.Studies have demonstrated that curcumin supplementation can modulate gut microbiota composition and function,leading to beneficial effects on gut health and homeostasis.Mechanisms underlying curcumin's therapeutic effects include immune modulation,neuroprotection,and inflammation regulation.However,challenges such as poor bioavailability and safety concerns remain significant hurdles to overcome.The interactions between curcumin and the gut microbiome hold promise for therapeutic interventions in a diverse range of health conditions.Further research is needed to optimize curcumin formulations,improve bioavailability,and address safety concerns.
基金supported by the Beijing Natural Science Foundation(L222126).
文摘Objective:To observed the effect of a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis(VVC)caused by Candida albicans.Methods:Temperature-sensitive in situ gels(ISG)were prepared using poloxamers 407 and 188 as matrices.The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29℃ and gelation time of 2.5 min.Results:Electroporation increased the transmucosal permeability of the model drug,doxorubicin and improved the antifungal effects of curcumin.In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG.In vivo pharmacodynamic experiments showed that,compared to the model group,curcumin ISG with electroporation inhibited the growth of C.albicans,alleviated vaginal mucosal edema,and reduced the inflammatory response.Conclusion:Curcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.
基金funded by the National Natural Science Foundation of China(Nos.82103885,81871521,82273672)Natural Science Foundation of Shanghai(Nos.21ZR1477700,20ZR1470300)+1 种基金the Shanghai Municipal Health Commission-Outstanding Youth Foundation of Public Health(No.GWV-10.2-YQ48)Sci Tech Funding by CSPFTZ Lingang Special Area Marine Biomedical Innovation Platform。
文摘Acute lung injury(ALI)is a critical respiratory disorder with a high mortality rate and is caused by several factors.Addressing oxidative stress and infiammation is a pivotal strategy for ALI treatment.In this study,we introduced a novel nanotherapeutic approach involving a curcumin-loaded ceria nanoenzyme delivery system tailored to counteract the multifaceted aspects of ALI.This system leverages the individual and combined effects of the components to provide a comprehensive therapeutic solution.The dual-action capability of this nanosystem was manifested by mitigating mitochondrial oxidative stress in lung epithelial cells and inhibiting the transient receptor potential melanosome-associated protein 2(TRPM2)-NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway,offering a highly effective therapeutic approach to ALI.Our findings reveal the underlying mechanisms of this innovative nanodelivery system,showcasing its potential as a versatile strategy for ALI treatment and encouraging further exploration of nanoenzyme-based therapies for ALI.
基金supported by the National Natural Science Foundation of China(Number:32060645)The Joint Special Project(Key Project)of Yunnan Province Local Undergraduate University(202101BA070001-036)+2 种基金The Joint Special Project(Surface Project)of Yunnan Province Local Undergraduate University(202101BA070001-172)the Science Research Fund Project for Education Department of Yunnan Province(Numbers:2023Y0876,2023Y0860,2023J0828)the Basic Research Special Project for Science and Technology Department of Yunnan Provincial(Number:202301AU070137).
文摘Soil salinization is a major abiotic stress that hampers plant development and significantly reduces agricultural productivity,posing a serious challenge to global food security.Akebia trifoliata(Thunb.)Koidz,a species within the genus Akebia Decne.,is valued for its use in food,traditionalmedicine,oil production,and as an ornamental plant.Curcumin,widely recognized for its pharmacological properties including anti-cancer,anti-neuroinflammatory,and anti-fibrotic effects,has recently drawn interest for its potential roles in plant stress responses.However,its impact on plant tolerance to saline-alkali stress remains poorly understood.In this study,the effects of curcumin on saline-alkali resistance in A.trifoliata were examined by subjecting plants to a saline-alkali solution containing 150 mmol/L sodium ions(a mixture of Na_(2)SO_(4),Na_(2)CO_(3),and NaHCO_(3)).Curcumin treatment under these stress conditions leads to anatomical improvements in leaf structure.Furthermore,A.trifoliatamaintained a favorable Na^(+)/K^(+)ratio through increased potassium uptake and reduced sodium accumulation.Biochemical analysis revealed elevated levels of proline,soluble sugars,and soluble proteins,along with improved activities of antioxidant enzymes such as superoxide dismutase(SOD),catalase(CAT),and peroxidase(POD).Similarly,the concentrations of hydrogen peroxide(H_(2)O_(2))and malondialdehyde(MDA)were significantly reduced.Transcriptome analysis under saline-alkali stress conditions showed that curcumin influenced seven keymetabolic pathways annotated in the Kyoto Encyclopedia of Genes and Genomes(KEGG)database,with differentially expressed unigenes primarily enriched in transcription factor families such as MYB,AP2/ERF,NAC,bHLH,and C2C2.Moreover,eight differentially expressed genes(DEGs)associated with plant hormone signal transduction were linked to the auxin and brassinosteroid pathways,critical for cell elongation and plant growth.These findings indicate that curcumin increases saline-alkali stress tolerance in A.trifoliata by modulating physiological,biochemical,and transcriptional responses,ultimately supporting improved growth under adverse conditions.
基金supported by the Science and Technology Program of Tianjin in China(Grant No.:23ZYJDSS00030).
文摘Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug delivery.In this study,we proposed a time-efficient method,PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles(GDNVs).Subsequently,curcumin(CUR)was loaded onto GDNV by ultrasonic incubation.The optimum conditions for ginger-derived nanovesicles loaded with curcumin(CG)were ultrasound time of 3 min,a carrier-to-drug ratio(GDNV:CUR)of 1:1.The study achieved a high loading capacity(94.027%±0.094%)and encapsulation efficiency(89.300%±0.344%).Finally,the drugs'in vivo distribution and anti-colitis activity were investigated in mice.CG was primarily distributed in the colon after oral administration.Compared to CUR and GDNV,CG was superior in improving disease activity,colon length,liver and spleen coefficients,myeloperoxidase activity,and biochemical factor levels in ulcerative colitis(UC)mice.In addition,CG plays a protective role against UC by modulating serum metabolite levels and gut flora.In summary,our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.
文摘The growth rate method was adopted to measure the inhibitory effect of curcumin,tetrahydrocurcumin,demethoxycurcumin,and bisdemethoxycurcumin on the mycelial growth of Botrytis cinerea and Colletotrichum gloeosporioides.The results showed that the four curcuminoids inhibited the mycelial growth of the two pathogens in a concentration-dependent manner.Bisdemethoxycurcumin at 600 mg/L exerted the strongest inhibitory effect on the mycelial growth of B.cinerea and C.gloeosporioides,with the relative inhibition rates of 98.19%and 100%,respectively;followed by demethoxycurcumin;curcumin exerted the worst inhibitory effect.Toxicity test results also showed that four curcuminoids all had a certain toxicity to B.cinerea and C.gloeosporioides,among which,bisdemethoxycurcumin exhibited the strongest toxicity,with the EC_(50)of 131.125 and 122.235 mg/L,respectively;while curcumin had the lowest toxicity,with the EC_(50)of 273.143 and 194.943 mg/L,respectively.
文摘Background:Breast cancer(BC)continues to be a significant global health issue,with a rising number of cases requiring ongoing research and innovation in treatment strategies.Curcumin(CUR),a natural compound derived from Curcuma longa,and similar compounds have shown potential in targeting the STAT3 signaling pathway,which plays a crucial role in BC progression.Aims:The aim of this study was to investigate the effects of curcumin and its analogues on BC based on cellular and molecular mechanisms.Materials&Methods:The literature search conducted for this study involved utilizing the Scopus,ScienceDirect,PubMed,and Google Scholar databases in order to identify pertinent articles.Results:This narrative review explores the potential of CUR and similar compounds in inhibiting STAT3 activation,thereby suppressing the proliferation of cancer cells,inducing apoptosis,and inhibiting metastasis.The review demonstrates that CUR directly inhibits the phosphorylation of STAT3,preventing its movement into the nucleus and its ability to bind to DNA,thereby hindering the survival and proliferation of cancer cells.CUR also enhances the effectiveness of other therapeutic agents and modulates the tumor microenvironment by affecting tumor-associated macrophages(TAMs).CUR analogues,such as hydrazinocurcumin(HC),FLLL11,FLLL12,and GOY030,show improved bioavailability and potency in inhibiting STAT3,resulting in reduced cell proliferation and increased apoptosis.Conclusion:CUR and its analogues hold promise as effective adjuvant treatments for BC by targeting the STAT3 signaling pathway.These compounds provide new insights into the mechanisms of action of CUR and its potential to enhance the effectiveness of BC therapies.
基金This research was financially supported by the National Key R&D Program of China(2019YFA0110600)the National Natural Science Foundation of China(82370932,81970917,82370929,81970916,81800947,82101077)+2 种基金the Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202102,RD03202302)Sichuan Science and Technology Program(2022NSFSC0002)Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021).
文摘Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.
基金Supported by the Natural Science Foundation of Gansu Province,China,No.20JR5RA356 and No.22JR5RA511the Lanzhou City Chengguan District Science and Technology Planning Project,No.2016-7-17.
文摘BACKGROUND Gastric cancer,characterized by a multifactorial etiology and high heterogeneity,continues to confound researchers in terms of its pathogenesis.Curcumin,a natural anticancer agent,exhibits therapeutic promise in gastric cancer.Its effects include promoting cell apoptosis,curtailing tumor angiogenesis,and enhancing sensitivity to radiation and chemotherapy.Long noncoding RNAs(lncRNAs)have garnered significant attention as biomarkers for early screening,diagnosis,treatment,and drug response because of their remarkable specificity and sensitivity.Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis,clinical staging,metastasis,drug sensitivity,and prognosis in gastric cancer.A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer develop-ment can provide novel insights for precision treatment and tailored management of patients with gastric cancer.This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregu-lating specific lncRNAs and modulating gastric cancer onset and progression.AIM To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis,proliferation,and invasion.Furthermore,these findings were validated in clinical samples.METHODS The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation,flow cytometry to investigate its effects on apoptosis,and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells.Western blotting was used to gauge changes in the protein expression levels of CDK6,CDK4,Bax,Bcl-2,caspase-3,P65,and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment.Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction(qRT-PCR)in BGC-823 and MGC-803 cells.AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis,proliferation,migration,and invasion of gastric cancer cells.Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways.RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics.RESULTS Curcumin induced apoptosis and hindered proliferation,migration,and invasion of gastric cancer cells in a dose-and time-dependent manner.LncRNA AC022424.2 was upregulated after curcumin treatment,and its knockdown enhanced cancer cell aggressiveness.LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways.LncRNA AC022424.2 downregulation was correlated with lymph node metastasis,making it a potential diagnostic and prognostic marker.CONCLUSION Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2.This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation.The results of this study enhance our understanding of gastric cancer development and precision treatment.
基金supported by the Science and Technology Commission of Shanghai Municipality(No.21430760800).
文摘The microphases and miscibility in binary curcumin(Cur)solid dispersions(SDs)with amorphous polyvinylpyrrolidone K30(PVP K30)and semi-crystalline poloxamer(P407)and poly(ethylene glycol)6000(PEG6000)as carriers were investigated by fluorescence contrasting utilizing confocal laser scanning microscopy.A super sensitive fluorophore P4 with typical aggregation-caused quenching properties was employed to stain the continuous polymer phases and contrasted with the autofluorescence of the model drug Cur.In addition,differential scanning calorimetry(DSC)and powder X-ray diffraction(PXRD)were utilized to assist in explanation of the fluorescence results.In all three SD systems,there is always a homogenous polymer phase stained by P4 and it is difficult to adulterate Cur crystals by P4.Cur-enriched rather than polymer-enriched domains could be detected.In the Cur-PVP K30 system,Cur exists in an amorphous form at a Cur loading level of 50%and below,while Cur crystallines phase out and continuously grow with the increase of Cur loading from 60%to 90%.The phase behaviors in the Cur-P407 and Cur-PEG 6000 systems are similar but with minor differences.In both systems,Cur phases out as clusters of drug-enriched domains at a loading level of 20%and below,which however cannot be correlated with crystallization,as evidenced by both DSC and PXRD.There is a transition from an amorphous to a crystalline state from 20%to 30%Cur loading,above which Cur crystallines can be detected.It is interesting that a co-mix phase of both Cur-and PEG 6000-enriched domains can be identified at Cur loading levels of 10%and less.Taking together,it is concluded that contrasting Cur autofluorescence with the signals of P4 proves to be a functional strategy to reveal multiple phases in the binary SD systems investigated.
文摘Inflammatory bowel disease(IBD)is a nonspecific inflammatory disease of the intestine that includes Crohn’s disease and ulcerative colitis.Because IBD is difficult to heal and easily relapses,it could worsen patient quality of life and increase economic burdens.Curcumin(CUR)is a bioactive component derived from the rhizome of turmeric(Curcuma longa).Many basic and clinical studies have shown that CUR can efficiently treat IBD by decreasing the activity of proinflammatory cytokines by communicating with transcription factors and signaling molecules.However,due to the limitations of being almost insoluble in aqueous solutions and having low oral bioavailability,it is important to select appropriate pharmaceutical preparations.
基金Supported by the National Nature Science Foundation of China,No.81273735 and No.82174319the Natural Science Foundation of Guangdong Province,China,No.2021A1515010961+1 种基金the Key-Area Research and Development Program of Guangdong Province,China,No.2020B1111100011the China Postdoctoral Science Foundation,China,No.2023M740859.
文摘BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.
基金funding from the Ministry of Education,Culture,Research,and Technology,Indonesia,through the PDKN Research Grant with Contract No.041/E5/PG.02.00.PL/2023.
文摘Curcumin is a natural polyphenol that is used in various traditional medicines.However,its inherent properties,such as its rapid degradation and metabolism,low bioavailability,and short half-life,are serious problems that must be resolved.To this end,a drug carrier incorporating natural magnetic cores in a zeolite framework was developed and applied to the loading of curcumin in ethanol solutions.In this system,curcumin is encapsulated in a zeolite Na(ZNA)magnetic core–shell structure(Fe@Si/ZNA),which can be easily synthesized using an in situ method.Synthesis of Fe_(3)O_(4) nanoparticles was carried out from natural materials using a co-precipitation method.Analysis of the prepared magnetic core–shell structures and composites was carried out using vibrating-sample magnetometery,Fourier transform infrared spectroscopy,transmission electron microscopy,and x-ray diffraction.The cumulative loading of curcumin in the ZNA composite with 9%nanoparticles was found to reach 90.70%with a relatively long half-life of 32.49 min.Stability tests of curcumin loading in the composite showed that adding magnetic particles to the zeolite framework also increased the stability of the composite structure.Adsorption kinetics and isotherm studies also found that the system follows the pseudo-second-order and Langmuir isotherm models.
基金supported by the National Key Research and Development Program of China(2022YFF1100205)the National Natural Science Foundation of China(31972105)the National Science Fund for Distinguished Young Scholars of China(31925031).
文摘The aim of this study is to investigate the feasibility of Maillard reaction products of Haematococcus pluvialis protein and galactose(HPP-GAL)for improving the bioactivities of curcumin(CUR)for alleviating alcoholic liver damage.CUR was embedded into HPP-GAL nanoparticles by the self-assembly of hydrogen bonding and hydrophobic interaction with the particle size around 200 nm.HPP-GAL enhanced the encapsulation efficiency and loading amount of CUR with the value of(89.21±0.33)%and(0.500±0.004)%,respectively.The stabilities of CUR under strong acid,salt ion stability and ultraviolet irradiation conditions were improved by the encapsulation.HPP-GAL-CUR nanoparticles exhibited excellent concentration-dependent in vitro antioxidant activities including DPPH and ABTS scavenging rates,and better protective effect on CUR against gastric acid environment as well as longer release of CUR in simulated intestinal fluid.In addition,the HPPGAL-CUR delivery system possessed liver targeting property due to the existence of GAL,which could effectively alleviate the alcohol-induced liver damage and the inflammation indexes by inhibiting the oxidative stress.Therefore,HPP-GAL-CUR nanoparticles might be a potential candidate system for the prevention of alcoholic liver damage in the future.