Plantago major L.,commonly known as plantain,waybread,or dooryard plantain,is a versatile medicinal plant with multiple therapeutic applications.Traditionally,various parts of the plant have been formulated into syrup...Plantago major L.,commonly known as plantain,waybread,or dooryard plantain,is a versatile medicinal plant with multiple therapeutic applications.Traditionally,various parts of the plant have been formulated into syrups,drops,ointments,vaginal suppositories,gargles,and roasted preparations to treat diverse ailments,such as liver disorders,earaches,epilepsy,asthma,stomachaches,diarrhea,constipation,polymenorrhea,and uterine disorders.The plant contains clinically valuable bioactive compounds,including polysaccharides,flavonoids,lipids,iridoid glycosides,caffeic acid derivatives,terpenoids,alkaloids,and organic acids.These bioactive constituents are the primary contributors to the plant’s broad spectrum of biological activities,including antioxidant,anti-inflammatory,antibacterial,antidiarrheal,hepatoprotective,antiviral,antiphage,antinociceptive,antiulcerogenic,antigenotoxic,and immunomodulatory effects of the plant.This review comprehensively summarizes the phytochemical composition,traditional medicinal applications,and biological properties of this multifunctional medicinal plant.展开更多
The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predomi...The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.展开更多
Typhonium flagelliforme(TF)is a Southeast Asian medicinal plant traditionally used for cancer,respiratory disorders,gastrointestinal complaints,wound healing,inflammation,and general health.Contemporary studies valida...Typhonium flagelliforme(TF)is a Southeast Asian medicinal plant traditionally used for cancer,respiratory disorders,gastrointestinal complaints,wound healing,inflammation,and general health.Contemporary studies validate these uses,showing potent anticancer,immunomodulatory,anti-inflammatory,gastroprotective,antibacterial,antioxidant,and wound-healing activities.Ethanol,dichloromethane,methanol,and ethyl acetate extracts exhibit strong cytotoxicity against breast(MCF-7,T47D),lung(NCI-H23),colon(WiDr),and leukemia(CEM-ss,WEHI-3)cells via apoptosis,telomerase inhibition,HER2/neu and BCL-2 suppression,and antiangiogenesis.Notably,2-octenoic acid and 2-hexenoic acid show exceptional activity(IC₅₀=2.66 and 3.10μg/mL)against MCF-7 cells.TF also restores lymphocyte proliferation,enhances macrophage activity,increases both CD4+and CD8+T-cell levels,and modulates cytokines(TNF-α,IL-1α,IL-10).Gastroprotective,anti-ulcer,antibacterial,antioxidant,and wound-healing effects further support traditional claims.Key phytochemicals include flavonoids(isovitexin,kaempferol,vitexin),phenolics(vanillin,4-hydroxybenzaldehyde),phytosterols(β-sitosterol,campesterol,stigmasterol,daucosterol),chlorophyll derivatives(pheophorbides),and long-chain fatty acids(linoleic,linolenic,oleic,stearic).These findings highlight TF as a source of multifunctional bioactive compounds,warranting further pharmacokinetic,safety,and clinical evaluation for evidence-based therapeutic development.展开更多
Objective:To synthesize silver nanoparticles from the biomass of cold tolerant strain of Spirulina platensis and evalute the synthesized nanoparticles against antibacterial and anticancer activity.Methods:Silver nanop...Objective:To synthesize silver nanoparticles from the biomass of cold tolerant strain of Spirulina platensis and evalute the synthesized nanoparticles against antibacterial and anticancer activity.Methods:Silver nanoparticles were synthesized by the algal culture and characterized by UV-vis spectroscopy,Fourier transform infrared spectroscopy,field emission scanning electron microscopy and X ray diffraction studies.Antibacterial activity has been studied with free nanoparticles adopting agar diffusion assay,biofilm inhibition assay and nanoparticles fabricated wound dressing against representative Gram-negative organism Pseudomonas aeruginosa and Gram-positive organism Staphylococcus aureus respectively.The in vitro anticancer activity of silver nanoparticles were screened against human Hep2 cell lines by means of MTT assay.Results:Reduction of silver ions by the algal culture was observed during 72 h of incubation and the synthesized nanoparticles were further characterized.Antibacterial study reveals both the strains were susceptible to free nanoparticles and fabricated wound dressing treatment.The in vitro anticancer activity of silver nanoparticles were screened against human Hep 2 cell lines by means of MTT assay which reveals that cell viability has been reduced as dose dependent manner.Conclusions:The observed results imply that silver nanoparticles synthesized from Spirulina platensis cold tolerant strain can be used as potential antibacterial and anticancerous agent.展开更多
Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive com...Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive compounds such as flavonoids and alkaloids,which influence multiple biological pathways.This review aims to summarise and critically analyse recent findings on the pharmacological properties of Passiflora incarnata L.,focusing on its neuropsychiatric,antioxidant,antimicrobial,and anticancer activities.A targeted literature search was conducted in PubMed,Scopus,Web of Science,and Google Scholar for peer-reviewed publications between 2000 to 2025.Relevant articles were screened,and a more appropriate article related to the objective of the review was selected.Some classical papers are also cited as per the requirement of the topic.Passiflora incarnata L.showed multifunctional medicinal properties with various applications in neuropsychiatry,oxidative stress management,antimicrobial agent,and as an anticancer agent.The U.S.Food and Drug Administration categorizes passionflower extracts as“generally recognized as safe”.However,most evidence remains preclinical,with methodological variation limiting generalisation.Standardised formulation,robust clinical trials,and in-depth in vivo studies are essential to establish its therapeutic relevance and safety in modern medicine.展开更多
Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer ...Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.展开更多
To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bisp...To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.展开更多
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge...Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.展开更多
To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(II...To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(III)2-benzoylpyridine thiosemicarbazone complexes to obtain an Au(III)agent(5b)with excellent cytotoxicity to cancer.The results show that 5b effectively inhibits tumor growth and its metastasis in vivo.Interestingly,we revealed a new mechanism of 5b inhibiting tumor growth and metastasis:5b releases ICD-related damage-associated molecular patterns(DAMPs),such as calreticulin(CRT),ATP and high mobility group box 1(HMGB1)by inducing endoplasmic reticulum stress(ERS)and mitochondrial dysfunction,which then stimulated an antitumor CD8^(+)T cell response and Foxp^(3+)T cell depletion,thus establishing long-action antitumor immunity.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com...BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.展开更多
Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a...Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.展开更多
Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourc...Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourced from clove and cannabis amongst others,and d-limonene is abundant in the Citrus genera.Apart from their use in agriculture,cosmetics,and food industries,these terpenes possess a wide range of therapeutic activities,including antimicrobial,analgesic,and anticancer activities.This review discusses the anticancer effects of these two compounds against malignant tumors including breast,lung,gastrointestinal,bone,blood,endometrial,and bladder cancer.Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60,HTRA,survivin,XIAP,Bcl-xL,and Bcl-2 and the upregulation of caspase 3,annexin V,p21,Bad,Bak,and Bax.The anticancer activity is also mediated by G1/M arrest,ROS induction,and JAK1/STAT activation.d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes,Bax,and caspase 3 and downregulating cyclin D1 and Bcl-2.These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.展开更多
To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex bas...To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex based on apoferritin(AFt).To this end,we rationally designed and synthesized a trinuclear Gd(Ⅲ)complex(Gd3)with strong T_(1)-weighted MRI performance and remarkable cytotoxicity against glioma cells in vitro.Subsequently,we constructed an AFt-Gd3 nanoparticle(NP)delivery system.AFt-Gd3 NPs not only penetrate BBB but also provide significant T_(1)-weighted MRI contrast for orthotopic glioma while effectively inhibiting glioma growth with minimal side effects in vivo.Furthermore,we elucidate the mechanism by which AFt-Gd3 NPs inhibit glioma growth:inducing apoptosis through chemodynamic therapy,blocking glutamine metabolism,and inhibiting energy metabolism.展开更多
Pinocembrin(PB)(5,7-dihydroxy flavanone)is a naturally occurring flavonoid sourced from propolis and Pinus spp.,with the formula C15H12O4 and moderate lipophilicity(log P approximately 2.1-2.5),which underlies both it...Pinocembrin(PB)(5,7-dihydroxy flavanone)is a naturally occurring flavonoid sourced from propolis and Pinus spp.,with the formula C15H12O4 and moderate lipophilicity(log P approximately 2.1-2.5),which underlies both its bioactivity and formulation challenges.In rodents,oral administration yields rapid absorption but extensive firstpass glucuronidation and sulfation,resulting in conjugates that dominate plasma,limit bioavailability(<10%)and confer a short half-life.In vitro,PB induces intrinsic mitochondrial apoptosis,downregulating Bcl-2,upregulating Bax,promoting cytochrome C release,and activating caspases-9/caspases-3 while inhibiting phosphoinositol-3 kinase/protein kinase B and STAT3 signaling,arresting cell-cycle progression,and suppressing metastatic markers(matrix metalloproteinase-9,vascular endothelial growth factor)across several cancer cell lines.Corresponding in vivo xenograft and orthotopic models demonstrate significant tumor growth inhibition,decreased Ki-67 indices,and increased cleaved caspase-3 without overt toxicity.To address solubility and clearance,MPEG-PDLLA micelles increased oral bioavailability by 5.3-fold and extended the half-life from 1.2 hours to 2.6 hours,while D-α-tocopheryl polyethylene glycol 1000 succinate liposomes achieved a 1.9-fold bioavailability increase and prolonged the half-life to 14.2 hours,indicating substantial pharmacokinetic(PK)enhancement and sustained systemic exposure in rodents.Toxicology studies report a no-observed-adverse-effect level≥500 mg/kg in rats with no mutagenicity,and phase I trials(0.5-10 mg/kg)confirm human tolerability.Key gaps remain in target validation,long-term toxicity,and prodrug development.This review is novel in its integration of pharmacology,formulation advances,safety assessments,and translational considerations for PB.To our knowledge,it is the first to systematically compare multiple nanocarrier systems in terms of their ability to improve oral bioavailability and PK parameters of PB.展开更多
Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitat...Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitations of single-drug chemotherapy,such as low response rates,ineffective treatment completion,and drug resistance,leading to aggressive proliferation and recurrence.This research focuses on utilizing the amphiphilic polymer quaternary ammonium palmitoyl glycol chitosan(GCPQ)as a carrier to load hydrophobic curcumin(CUR)and hydrophilic doxorubicin(DOX)to reach the desired target and release the cargo upon exogenous stimuli of ultrasound.Methods:The nanoformulation synthesized using a biocompatible approach,resulting in a stable DOX-CUR-GCPQ nano-formulation upon physicochemical characterization and in vitro analysis using ultrasound.Results:The mean hydrodynamic diameter of DOX-CUR-GCPQ nanomicelles was measured as 95±1.23 nm,PDI 0.32±0.87,zeta potential−35±1.78 mV,and encapsulation efficiency 87.32%±0.3 and 79.42%±0.5 for DOX and CUR respectively.Biocompatibility studies revealed minimal hemolytic activity and biocompatible behavior of the nano-formulation,the co-loaded polymer-based nano-formulation when exposed to Ultrasound at a frequency of 1.5 MHz,for 40 s,on Hep2c cancer cell lines showed a higher release of 89% after 48 h.Moreover,a higher amount of drug internalized within the cells(P<0.0001).Conclusion:The exhibited lower cell viability and IC50(70μg/mL)which demonstrated that ultrasound waves likely facilitated the penetration and uptake of the amphiphilic polymer encapsulating dual drugs into the Hep2c cancer cells,allowing for more efficient delivery of the drugs(DOX and CUR)and broadens the spectrum of anticancer therapy.展开更多
The Tragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity...The Tragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity properties and has a unique geographical location.This study is the first attempt to investigate the antioxidant,anticancer,and genoprotective properties of the aqueous extracts from the leaves(AQ-TrDL)and stems(AQ-TrDS)of this plant.AQ-TrDL and AQ-TrDS demonstrated significant amounts of phenolic and flavonoid contents.GC-HRMS identified various phytochemicals belonging to different classes,like carboxylic acids,fatty acid derivatives,phenols,and triterpenoids.DPPH,Superoxide,FRAP,and ABTS antioxidant assays showed that AQ-TrDS exhibited stronger radical scavenging activities than AQ-TrDL,with IC_(50)values ranging from 40.31 to 73.58μg/mL.Cytotoxicity tests revealed that AQ-TrDS significantly inhibited the growth of cancer cells inMCF-7,HCT-116,HeLa,and A-549 cell lines,with over 50%inhibition observed at concentrations ranging from 56.62 to 98.32μg/mL.Importantly,minimal effects were seen in normal fibroblast L-929 cells,with GI50 values over 434μg/mL.Additionally,genoprotective tests showed that AQ-TrDS effectively reduced“H_2)O_(2)”-induced DNA damage in lymphocytes,decreasing damage by up to 61.18%at a concentration of 320μg/mL.HPLC analysis of amino acids identified 10 amino acids in T.dubius leaves and 14 in stems,showing its nutritional value.Overall,these findings highlight the biomedical potential of T.dubius aqueous extracts for developing new pharmaceutical agents.展开更多
Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the devel...Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.展开更多
For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in...For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in T1-weighted magnetic resonance imaging(MRI)and cytotoxicity to TNBC cells.In addition,we constructed a GdCu@apoferritin(AFt)nanoparticles(NPs)delivery system.GdCu and GdCu@AFt NPs significantly inhibited the migration and invasion of MDA-MB-231 cells in vitro.GdCu can significantly inhibit the growth and metastasis of TNBC in vivo.GdCu@AFt NPs not only improved the targeting ability of GdCu,showed an enhanced performance of MRI and tumor-growth inhibition,but also decreased the systemic toxicity of GdCu in vivo.We demonstrated that GdCu and GdCu@AFt NPs prevented the growth and metastasis of TNBC by inducing mitochondria-mediated apoptosis and inhibiting cancer cell stemness.The remarkable MRI,anticancer and anti-metastasis capabilities of GdCu and GdCu@AFt NPs make them promising agents for the targeted theranostics of TNBC.展开更多
Cancer ranks among the foremost causes of mortality.Health organizations indicate that prevention,through healthy and balanced lifestyles,is the key factor for decreasing cancer risk and,consequently,reducing cancer p...Cancer ranks among the foremost causes of mortality.Health organizations indicate that prevention,through healthy and balanced lifestyles,is the key factor for decreasing cancer risk and,consequently,reducing cancer prevalence and mortality.There is growing interest in discovering dietary patterns and food phytochemicals with potential anticancer effects to support public health strategies.Naturopathy emphasizes cancer prevention primarily through a plant-based diet abundant in functional foods,which enhance the innate defenses of the body against cancer.This article offers an analysis and overview of plant-based functional foods that have demonstrated anticancer properties in scientific studies,focusing on the mechanisms through which phytochemical compounds exert their chemopreventive actions.The plant-based functional foods and their constitution in phytochemicals,scientifically recognized for reducing cancer risk by various actions,are explored—citrus fruit(citrusflavonoids),berries(anthocyanins),pomegranate(ellagic acid),tomato(lycopene),soybeans and soy-based foods(isoflavones),cruciferous vegetables(indole-3-carbinol and sulforaphane),garlic(allicin)and onions(onionin A),green tea(catechins),and turmeric(curcumin).Cancer che-moprevention mechanisms involve antioxidants,anti-inflammatory effects,enhanced detoxification,carcinogen activation block-ade,antiangiogenesis,cell proliferation inhibition,apoptosis,cell cycle arrest,hormone-dependent carcinogenesis suppression,and epigenetic regulation.While numerous studies investigate the health-promoting potential of phytochemicals,it is important to emphasize that cancer prevention is multifactorial,influenced by many factors,such as other lifestyle aspects,genetics,and environment.Future perspectives will concentrate on personalized nutrition and nutrigenomics to enhance cancer prevention strategies,integrating scientific evidence-based naturopathic strategies for more effective cancer prevention.展开更多
Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sis...Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sistance and immunosuppressive tumor microenvironment.This review reports the latest studies on combination therapies for mesothelioma,focusing on the potential of integrating chemotherapeutic agents,molecularly targeted agents,vaccines and natural bioactive compounds such as polyphenols.Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients.Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments.Moreover,natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance.While several combination strategies are under clinical investigation,further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.展开更多
文摘Plantago major L.,commonly known as plantain,waybread,or dooryard plantain,is a versatile medicinal plant with multiple therapeutic applications.Traditionally,various parts of the plant have been formulated into syrups,drops,ointments,vaginal suppositories,gargles,and roasted preparations to treat diverse ailments,such as liver disorders,earaches,epilepsy,asthma,stomachaches,diarrhea,constipation,polymenorrhea,and uterine disorders.The plant contains clinically valuable bioactive compounds,including polysaccharides,flavonoids,lipids,iridoid glycosides,caffeic acid derivatives,terpenoids,alkaloids,and organic acids.These bioactive constituents are the primary contributors to the plant’s broad spectrum of biological activities,including antioxidant,anti-inflammatory,antibacterial,antidiarrheal,hepatoprotective,antiviral,antiphage,antinociceptive,antiulcerogenic,antigenotoxic,and immunomodulatory effects of the plant.This review comprehensively summarizes the phytochemical composition,traditional medicinal applications,and biological properties of this multifunctional medicinal plant.
基金supported by the National Key R&D Program of China(2024YFF1306700)the Key Project of Basic Research of Yunnan Province,China(202301AS070001)the Regional Innovative Development Joint Fund of NSFC(U23A20149).
文摘The global burden of cancer,with over 19 million new cases annually,underscores the urgent need for effective therapies.Among the most promising anticancer compounds is camptothecin(CPT),a monoterpene alkaloid predominantly derived from Nothapodytes species.Despite its significantpharmaceutical value,the exploitation of such Threatened Plant Species with Widespread Distribution(TPSWD),particularly driven by the global demand for natural compounds in anticancer therapies,presents a paradox in which their widespread distribution fails to ensure their secure conservation status.Furthermore,the lack of in-depth biogeographic and systematic studies complicates efforts to balance resource utilization with biodiversity preservation.The asymmetric distribution of CPT within plant taxa,along with limited knowledge of its biosynthetic pathways and the enzymes and genes involved,further hampers sustainable production.Here,we review the current knowledge on the production and protection of Nothapodytes,focusing on their plant resources,active ingredients,and natural drug derivatives.We also explore strategies for rescuing and sustainably utilizing Nothapodytes,including biotechnological advancements and integrated conservation practices.Finally,we propose future directions to address conservation challenges,ensuring a sustainable supply of CPT while safeguarding these TPSWD species.
基金the Ministry of Higher Education(MOHE),Malaysia,for funding this research through grant no.IF070-2020the Science and Technology Research Partnership for Sustainable Development(SATREPS)program,administered by the Japan Agency for Medical Research and Development(AMED)and the Japan International Cooperation Agency(JICA).
文摘Typhonium flagelliforme(TF)is a Southeast Asian medicinal plant traditionally used for cancer,respiratory disorders,gastrointestinal complaints,wound healing,inflammation,and general health.Contemporary studies validate these uses,showing potent anticancer,immunomodulatory,anti-inflammatory,gastroprotective,antibacterial,antioxidant,and wound-healing activities.Ethanol,dichloromethane,methanol,and ethyl acetate extracts exhibit strong cytotoxicity against breast(MCF-7,T47D),lung(NCI-H23),colon(WiDr),and leukemia(CEM-ss,WEHI-3)cells via apoptosis,telomerase inhibition,HER2/neu and BCL-2 suppression,and antiangiogenesis.Notably,2-octenoic acid and 2-hexenoic acid show exceptional activity(IC₅₀=2.66 and 3.10μg/mL)against MCF-7 cells.TF also restores lymphocyte proliferation,enhances macrophage activity,increases both CD4+and CD8+T-cell levels,and modulates cytokines(TNF-α,IL-1α,IL-10).Gastroprotective,anti-ulcer,antibacterial,antioxidant,and wound-healing effects further support traditional claims.Key phytochemicals include flavonoids(isovitexin,kaempferol,vitexin),phenolics(vanillin,4-hydroxybenzaldehyde),phytosterols(β-sitosterol,campesterol,stigmasterol,daucosterol),chlorophyll derivatives(pheophorbides),and long-chain fatty acids(linoleic,linolenic,oleic,stearic).These findings highlight TF as a source of multifunctional bioactive compounds,warranting further pharmacokinetic,safety,and clinical evaluation for evidence-based therapeutic development.
文摘Objective:To synthesize silver nanoparticles from the biomass of cold tolerant strain of Spirulina platensis and evalute the synthesized nanoparticles against antibacterial and anticancer activity.Methods:Silver nanoparticles were synthesized by the algal culture and characterized by UV-vis spectroscopy,Fourier transform infrared spectroscopy,field emission scanning electron microscopy and X ray diffraction studies.Antibacterial activity has been studied with free nanoparticles adopting agar diffusion assay,biofilm inhibition assay and nanoparticles fabricated wound dressing against representative Gram-negative organism Pseudomonas aeruginosa and Gram-positive organism Staphylococcus aureus respectively.The in vitro anticancer activity of silver nanoparticles were screened against human Hep2 cell lines by means of MTT assay.Results:Reduction of silver ions by the algal culture was observed during 72 h of incubation and the synthesized nanoparticles were further characterized.Antibacterial study reveals both the strains were susceptible to free nanoparticles and fabricated wound dressing treatment.The in vitro anticancer activity of silver nanoparticles were screened against human Hep 2 cell lines by means of MTT assay which reveals that cell viability has been reduced as dose dependent manner.Conclusions:The observed results imply that silver nanoparticles synthesized from Spirulina platensis cold tolerant strain can be used as potential antibacterial and anticancerous agent.
文摘Passiflora incarnata L.,commonly known as passionflower,is traditionally cultivated as an ornamental plant but has demonstrated diverse therapeutic potential.Its pharmacological effects are attributed to bioactive compounds such as flavonoids and alkaloids,which influence multiple biological pathways.This review aims to summarise and critically analyse recent findings on the pharmacological properties of Passiflora incarnata L.,focusing on its neuropsychiatric,antioxidant,antimicrobial,and anticancer activities.A targeted literature search was conducted in PubMed,Scopus,Web of Science,and Google Scholar for peer-reviewed publications between 2000 to 2025.Relevant articles were screened,and a more appropriate article related to the objective of the review was selected.Some classical papers are also cited as per the requirement of the topic.Passiflora incarnata L.showed multifunctional medicinal properties with various applications in neuropsychiatry,oxidative stress management,antimicrobial agent,and as an anticancer agent.The U.S.Food and Drug Administration categorizes passionflower extracts as“generally recognized as safe”.However,most evidence remains preclinical,with methodological variation limiting generalisation.Standardised formulation,robust clinical trials,and in-depth in vivo studies are essential to establish its therapeutic relevance and safety in modern medicine.
基金supported by FCT/MCTES UIDP/05608/2020(https://doi.org/10.54499/UIDP/05608/2020,accessed on 01 July 2025)UIDB/05608/2020(https://doi.org/10.54499/UIDB/05608/2020,accessed on 01 July 2025).Institutional.
文摘Objectives:Colorectal cancer(CRC)is a major global health burden,and Urolithin A(Uro-A)has emerged as a promising anticancer agent.This systematic review aims to synthesize current in vitro evidence on the anticancer effects of Uro-A in CRC,highlighting effective concentration ranges,exposure times,relevant outcomes,and underlying molecular mechanisms.Methods:Following PRISMA 2020 guidelines,a systematic search was conducted in PubMed,Scopus,and Web of Science using the following strategy:(colorectal cancer)AND(urolithin a)OR(3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one).Eligibility criteria were defined by the PICO framework:(P)in vitro CRC cell models;(I)Uro-A alone or combined treatments;(C)No intervention,vehicle or other treatments;(O)Relevant anticancer outcomes of Uro-A in CRC.Only original,full-text,in vitro studies in English were included.Risk of bias was assessed using ToxRTool.A qualitative synthesis was performed due to the heterogeneity of the included studies.Results:Fifteen studies met inclusion criteria,involving CRC cell lines(Caco-2,HCT-116,HT-29,SW480,SW620)and normal colon fibroblasts(CCD18-Co).Uro-A inhibited CRC cell proliferation,clonogenic growth,cancer stem cells properties,migration,and invasion,and induced cell cycle arrest,apoptosis,autophagy,and senescence,through modulation of key signaling pathways and proteins.Co-treatments with conventional chemotherapeutics and microbiota-derived metabolites showed additive or synergistic effects.Discussion:The findings support UroA’s potential as a preventive or adjuvant agent in CRC treatment.However,preclinical nature of the evidence and methodological heterogeneity hinder clinical extrapolation to in vivo contexts.Human clinical trials are necessary to overcome these limitations.Other:This review was registered in PROSPERO(CRD420251070874)and supported by FCT/MCTES UIDP/05608/2020 and UIDB/05608/2020.Institutional.
文摘To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2.
基金support from the National Natural Science Foundation of China(Nos.22277056,21977052)the Distinguished Young Scholars of Jiangsu Province(No.BK20230006)+2 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20230977,BK20231090)the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(No.23KJB150020)the Jiangsu Excellent Postdoctoral Program(No.2022ZB758)。
文摘Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT.
基金supported by the Natural Science Foundation of Guangxi(No.2022GXNSFGA035003)the National Natural Science Foundation of China(No.22077021).
文摘To treat cancer and inhibit its metastasis to the greatest extent,we proposed to develop an Au(III)agent to induce immunogenic cell death(ICD)and establish long-term immunity.To this end,we optimized a series of Au(III)2-benzoylpyridine thiosemicarbazone complexes to obtain an Au(III)agent(5b)with excellent cytotoxicity to cancer.The results show that 5b effectively inhibits tumor growth and its metastasis in vivo.Interestingly,we revealed a new mechanism of 5b inhibiting tumor growth and metastasis:5b releases ICD-related damage-associated molecular patterns(DAMPs),such as calreticulin(CRT),ATP and high mobility group box 1(HMGB1)by inducing endoplasmic reticulum stress(ERS)and mitochondrial dysfunction,which then stimulated an antitumor CD8^(+)T cell response and Foxp^(3+)T cell depletion,thus establishing long-action antitumor immunity.
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.
基金Supported by Malaysian Ministry of Higher Education through the Fundamental Research Grant Scheme,No.FP103-2019.
文摘Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.
文摘Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms.Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants.Beta-caryophyllene can be sourced from clove and cannabis amongst others,and d-limonene is abundant in the Citrus genera.Apart from their use in agriculture,cosmetics,and food industries,these terpenes possess a wide range of therapeutic activities,including antimicrobial,analgesic,and anticancer activities.This review discusses the anticancer effects of these two compounds against malignant tumors including breast,lung,gastrointestinal,bone,blood,endometrial,and bladder cancer.Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60,HTRA,survivin,XIAP,Bcl-xL,and Bcl-2 and the upregulation of caspase 3,annexin V,p21,Bad,Bak,and Bax.The anticancer activity is also mediated by G1/M arrest,ROS induction,and JAK1/STAT activation.d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes,Bax,and caspase 3 and downregulating cyclin D1 and Bcl-2.These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.
基金supported by the Natural Science Foundation of Guangxi(2022GXNSFGA035003)Natural Science Foundation of China(82404419,22077021)the Guangxi"Bagui"Scholar Program to F.Y.
文摘To effectively penetrate the blood-brain barrier(BBB)and integrate magnetic resonance imaging(MRI)diagnosis and multitarget therapy for orthotopic glioma,we proposed to develop a multinuclear gadolinium(Gd)complex based on apoferritin(AFt).To this end,we rationally designed and synthesized a trinuclear Gd(Ⅲ)complex(Gd3)with strong T_(1)-weighted MRI performance and remarkable cytotoxicity against glioma cells in vitro.Subsequently,we constructed an AFt-Gd3 nanoparticle(NP)delivery system.AFt-Gd3 NPs not only penetrate BBB but also provide significant T_(1)-weighted MRI contrast for orthotopic glioma while effectively inhibiting glioma growth with minimal side effects in vivo.Furthermore,we elucidate the mechanism by which AFt-Gd3 NPs inhibit glioma growth:inducing apoptosis through chemodynamic therapy,blocking glutamine metabolism,and inhibiting energy metabolism.
文摘Pinocembrin(PB)(5,7-dihydroxy flavanone)is a naturally occurring flavonoid sourced from propolis and Pinus spp.,with the formula C15H12O4 and moderate lipophilicity(log P approximately 2.1-2.5),which underlies both its bioactivity and formulation challenges.In rodents,oral administration yields rapid absorption but extensive firstpass glucuronidation and sulfation,resulting in conjugates that dominate plasma,limit bioavailability(<10%)and confer a short half-life.In vitro,PB induces intrinsic mitochondrial apoptosis,downregulating Bcl-2,upregulating Bax,promoting cytochrome C release,and activating caspases-9/caspases-3 while inhibiting phosphoinositol-3 kinase/protein kinase B and STAT3 signaling,arresting cell-cycle progression,and suppressing metastatic markers(matrix metalloproteinase-9,vascular endothelial growth factor)across several cancer cell lines.Corresponding in vivo xenograft and orthotopic models demonstrate significant tumor growth inhibition,decreased Ki-67 indices,and increased cleaved caspase-3 without overt toxicity.To address solubility and clearance,MPEG-PDLLA micelles increased oral bioavailability by 5.3-fold and extended the half-life from 1.2 hours to 2.6 hours,while D-α-tocopheryl polyethylene glycol 1000 succinate liposomes achieved a 1.9-fold bioavailability increase and prolonged the half-life to 14.2 hours,indicating substantial pharmacokinetic(PK)enhancement and sustained systemic exposure in rodents.Toxicology studies report a no-observed-adverse-effect level≥500 mg/kg in rats with no mutagenicity,and phase I trials(0.5-10 mg/kg)confirm human tolerability.Key gaps remain in target validation,long-term toxicity,and prodrug development.This review is novel in its integration of pharmacology,formulation advances,safety assessments,and translational considerations for PB.To our knowledge,it is the first to systematically compare multiple nanocarrier systems in terms of their ability to improve oral bioavailability and PK parameters of PB.
文摘Background:Stimuli-responsive drug delivery systems introduced nowadays to enable enhanced drug release upon exogenous stimulus.Research focuses on developing systems for co-administration of drugs to overcome limitations of single-drug chemotherapy,such as low response rates,ineffective treatment completion,and drug resistance,leading to aggressive proliferation and recurrence.This research focuses on utilizing the amphiphilic polymer quaternary ammonium palmitoyl glycol chitosan(GCPQ)as a carrier to load hydrophobic curcumin(CUR)and hydrophilic doxorubicin(DOX)to reach the desired target and release the cargo upon exogenous stimuli of ultrasound.Methods:The nanoformulation synthesized using a biocompatible approach,resulting in a stable DOX-CUR-GCPQ nano-formulation upon physicochemical characterization and in vitro analysis using ultrasound.Results:The mean hydrodynamic diameter of DOX-CUR-GCPQ nanomicelles was measured as 95±1.23 nm,PDI 0.32±0.87,zeta potential−35±1.78 mV,and encapsulation efficiency 87.32%±0.3 and 79.42%±0.5 for DOX and CUR respectively.Biocompatibility studies revealed minimal hemolytic activity and biocompatible behavior of the nano-formulation,the co-loaded polymer-based nano-formulation when exposed to Ultrasound at a frequency of 1.5 MHz,for 40 s,on Hep2c cancer cell lines showed a higher release of 89% after 48 h.Moreover,a higher amount of drug internalized within the cells(P<0.0001).Conclusion:The exhibited lower cell viability and IC50(70μg/mL)which demonstrated that ultrasound waves likely facilitated the penetration and uptake of the amphiphilic polymer encapsulating dual drugs into the Hep2c cancer cells,allowing for more efficient delivery of the drugs(DOX and CUR)and broadens the spectrum of anticancer therapy.
基金supported by Research institute/Center Supporting Program(RICSP-25-3),King Saud University,Riyadh,Saudi Arabia.
文摘The Tragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity properties and has a unique geographical location.This study is the first attempt to investigate the antioxidant,anticancer,and genoprotective properties of the aqueous extracts from the leaves(AQ-TrDL)and stems(AQ-TrDS)of this plant.AQ-TrDL and AQ-TrDS demonstrated significant amounts of phenolic and flavonoid contents.GC-HRMS identified various phytochemicals belonging to different classes,like carboxylic acids,fatty acid derivatives,phenols,and triterpenoids.DPPH,Superoxide,FRAP,and ABTS antioxidant assays showed that AQ-TrDS exhibited stronger radical scavenging activities than AQ-TrDL,with IC_(50)values ranging from 40.31 to 73.58μg/mL.Cytotoxicity tests revealed that AQ-TrDS significantly inhibited the growth of cancer cells inMCF-7,HCT-116,HeLa,and A-549 cell lines,with over 50%inhibition observed at concentrations ranging from 56.62 to 98.32μg/mL.Importantly,minimal effects were seen in normal fibroblast L-929 cells,with GI50 values over 434μg/mL.Additionally,genoprotective tests showed that AQ-TrDS effectively reduced“H_2)O_(2)”-induced DNA damage in lymphocytes,decreasing damage by up to 61.18%at a concentration of 320μg/mL.HPLC analysis of amino acids identified 10 amino acids in T.dubius leaves and 14 in stems,showing its nutritional value.Overall,these findings highlight the biomedical potential of T.dubius aqueous extracts for developing new pharmaceutical agents.
文摘Background:The increasing incidence of cancers and infectious diseases worldwide presents a significant public health challenge that requires immediate intervention.Our strategy to tackle this issue involves the development of pharmaceutical formulations that combine phytopolyphenols(P),targeted drugs(T),and metal ions(M),collectively referred to as PTM regimens.The diverse pharmacological properties of PTM regimens are hypothesized to effectively reduce the risk factors associated with both cancers and infectious diseases.Methods:The effects of the pharmaceutical agents on the proliferation of cultured cancer cells and pathogens were assessed after 72 h and 48 h,respectively,using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide)assay and optical density at 600 nm(OD600).The synergistic effects of drug combinations were evaluated by combination index(CI),where CI<1 indicates synergism,CI=1 indicates addition,and CI>1 indicates antagonism.Efficacy index(EI)was also calculated.Assays of efflux pump ATPase activities were conducted using a colorimetric method.Results:This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols(specifically curcumin(C)and green tea polyphenols(G)),repurposed drugs(memantine(Mem),thioridazine(TRZ),cisplatin(Cis),and 5-fluorouracil(5FU)),and ZnSO_(4)(Zn)across three cultured cancer cell lines and four cultured pathogens.The most effective regimens,GC·Mem·Zn and GC·TRZ·Zn,significantly enhanced the anticancer efficacy(EI)of cisplatin across the three cancer lines(OECM-1,A549 and DLD-1)by 7,11 and 21;7,9,and 17 fold,respectively,while the enhancements for 5-fluorouracil were 5,6 and 12;5,5 and 9 fold,respectively.Furthermore,these PTM regimens demonstrated substantial synergistic inhibition of Na^(+)-K^(+)-Mg^(2+)-ATPase and Mg^(2+)-ATPase in the cultured cancer cells,as well as a reduction in biofilm formation by the four cultured pathogens,suggesting their potential to address the challenges of multidrug resistance in cancers and infectious diseases.Conclusion:Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy,particularly regarding their synergistic selective anticancer efficacy,inhibition of efflux pump ATPase,and antibiofilm formation of pathogens,these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents.Further preclinical and clinical investigations are warranted.
基金supported by the Natural Science Foundation of China(No.22077021)the Natural Science Foundation of Guangxi(No.2022GXNSFGA035003).
文摘For precise personalized treatment of triple-negative breast cancer(TNBC)and inhibition of its metastasis,we innovatively designed and synthesized a gadolinium(Ⅲ)-copper(Ⅰ)complex(GdCu)with remarkable performance in T1-weighted magnetic resonance imaging(MRI)and cytotoxicity to TNBC cells.In addition,we constructed a GdCu@apoferritin(AFt)nanoparticles(NPs)delivery system.GdCu and GdCu@AFt NPs significantly inhibited the migration and invasion of MDA-MB-231 cells in vitro.GdCu can significantly inhibit the growth and metastasis of TNBC in vivo.GdCu@AFt NPs not only improved the targeting ability of GdCu,showed an enhanced performance of MRI and tumor-growth inhibition,but also decreased the systemic toxicity of GdCu in vivo.We demonstrated that GdCu and GdCu@AFt NPs prevented the growth and metastasis of TNBC by inducing mitochondria-mediated apoptosis and inhibiting cancer cell stemness.The remarkable MRI,anticancer and anti-metastasis capabilities of GdCu and GdCu@AFt NPs make them promising agents for the targeted theranostics of TNBC.
文摘Cancer ranks among the foremost causes of mortality.Health organizations indicate that prevention,through healthy and balanced lifestyles,is the key factor for decreasing cancer risk and,consequently,reducing cancer prevalence and mortality.There is growing interest in discovering dietary patterns and food phytochemicals with potential anticancer effects to support public health strategies.Naturopathy emphasizes cancer prevention primarily through a plant-based diet abundant in functional foods,which enhance the innate defenses of the body against cancer.This article offers an analysis and overview of plant-based functional foods that have demonstrated anticancer properties in scientific studies,focusing on the mechanisms through which phytochemical compounds exert their chemopreventive actions.The plant-based functional foods and their constitution in phytochemicals,scientifically recognized for reducing cancer risk by various actions,are explored—citrus fruit(citrusflavonoids),berries(anthocyanins),pomegranate(ellagic acid),tomato(lycopene),soybeans and soy-based foods(isoflavones),cruciferous vegetables(indole-3-carbinol and sulforaphane),garlic(allicin)and onions(onionin A),green tea(catechins),and turmeric(curcumin).Cancer che-moprevention mechanisms involve antioxidants,anti-inflammatory effects,enhanced detoxification,carcinogen activation block-ade,antiangiogenesis,cell proliferation inhibition,apoptosis,cell cycle arrest,hormone-dependent carcinogenesis suppression,and epigenetic regulation.While numerous studies investigate the health-promoting potential of phytochemicals,it is important to emphasize that cancer prevention is multifactorial,influenced by many factors,such as other lifestyle aspects,genetics,and environment.Future perspectives will concentrate on personalized nutrition and nutrigenomics to enhance cancer prevention strategies,integrating scientific evidence-based naturopathic strategies for more effective cancer prevention.
基金funded by a grant fromtheMinistero dell’Universita e della Ricerca,PRIN 2022 PNRR grant(Prot.P2022LZXNWto R.B.).
文摘Mesothelioma is a rare and aggressive cancer with a poor prognosis and limited therapeutic options.Despite recent advances,conventional treatment approaches remain largely ineffective due to late diagnosis,chemore-sistance and immunosuppressive tumor microenvironment.This review reports the latest studies on combination therapies for mesothelioma,focusing on the potential of integrating chemotherapeutic agents,molecularly targeted agents,vaccines and natural bioactive compounds such as polyphenols.Clinical and preclinical studies demonstrate that integrating immune-modulating drugs or molecular inhibitors with chemotherapy can improve survival and reduce tumor progression in mesothelioma models and patients.Vaccine-based strategies show potential for inducing host-persistent immune responses when combined with conventional treatments.Moreover,natural compounds such as polyphenols show synergistic effects with chemotherapeutics and targeted agents by modulating several signaling pathways involved in cancer cell growth and progression and by overcoming drug resistance.While several combination strategies are under clinical investigation,further studies are needed to develop more effective and personalized therapeutic approaches that could be translated into standardized treatment protocols.
