[Objective] The research aimed to lay a foundation for the screening of cell lines producing secondary metabolites of Brucea javanica(L.)Merr.[Method] The insecticidal activities of the extracts from branch and 3 diff...[Objective] The research aimed to lay a foundation for the screening of cell lines producing secondary metabolites of Brucea javanica(L.)Merr.[Method] The insecticidal activities of the extracts from branch and 3 different types of calluses of Brucea javanica(L.)Merr.was detected through methods of leaf disc and potted seedlings against the diamond back moth.[Result] Extracts from four kinds of Brucea javanica(L.)Merr.tissues assumed both the activities of antifeedant and oviposition deterrency against the diamond back moth.Antifeedant effect of extracts was in turn the callus C< callus B< callus A< branches.Oviposition deterrency activity of the extracts was in turn the callus A> branch > callus B>callus C.The insecticidal activities of callus A and B were higher than that of the callus C.[Conclusion] The results show that insecticidal activity of callus and its growth rate is inversely proportional.展开更多
Objective:The morbidity of malignant melanoma keeps increasing annually.It has high risks of metastasis,drug resistance,and poor prognosis in clinics.Moreover,the available medicines used commonly,such as dacarbazine,...Objective:The morbidity of malignant melanoma keeps increasing annually.It has high risks of metastasis,drug resistance,and poor prognosis in clinics.Moreover,the available medicines used commonly,such as dacarbazine,temozolomide,the v-Raf murine sarcoma viral oncogene homolog B1(BRAF)inhibitor vemurafenib,and the programmed cell death protein 1 inhibitor pembrolizumab,have some limitations at some extent.Therefore,a more effective therapeutic strategy is still urgently necessary.Methods:In this study,Brucea javanica(L.)Merr.globulins were hydrolyzed with pepsin,then ultra-filtrated to collect small molecular peptides(≤3 kDa).The peptides were then analyzed by antiproliferative assay,cell-cycle distribution,apoptosis assay,and in vitro wound-scratch assay.Finally,western blotting was conducted to elucidate the underlying anti-melanoma mechanism.Results:The small molecular peptide from B.javanica significantly inhibited malignant melanoma cell proliferation with the IC_(50) of 2.72 mg/mL for 72 h.Further analysis indicated that B.javanica peptides arrested cell cycle at the S and G2/M phases and induced apoptosis by upregulating p21,p53,Bax,caspase-3,and cleaved PARP while downregulating Bcl-2 expression.The inhibitory migration effects were also confirmed by wound-healing assay.Conclusion:The small molecular biopeptides from B.javanica may be a promising bioactive agent candidate for melanoma treatment.展开更多
Background:Brucea javanica oil(BJO),distributed primarily in Southeast Asia,has long been utilized as a therapeutic agent for treating malignancies.However,its anticancer mechanisms are not clearly understood.The obje...Background:Brucea javanica oil(BJO),distributed primarily in Southeast Asia,has long been utilized as a therapeutic agent for treating malignancies.However,its anticancer mechanisms are not clearly understood.The objective of this study was to examine the mechanisms underlying its treatment of hepatocellular carcinoma cells.Methods:CCK8 assay was used to evaluate cell viability.Hoechst33342 staining and flow cytometry analyses were used to examine apoptosis.Mito-Tracker Red CMXRos kit was used to measure the membrane potential of mitochondria.ATP assay kit was used to evaluate ATP levels.Western blots were used to assess the presence of AKT,adenosine monophosphate-activated protein kinase,Caspase3,Caspase9,Bax,and Bcl-2.Results:BJO inhibited the proliferation of hepatocellular carcinoma cells HepG2 in a time-and dose-dependent manner.It induced apoptosis,with the percentage of cells treated with 50–150μg/mL BJO increasing from 8.01%to 28.02%in a concentration-dependent manner(P<0.05,when 50μg/mL of BJO group compared with the control group;P<0.001,when 100 or 150μg/mL of BJO group compared with the control group).After exposed to BJO,the expression of C-caspase3,C-caspase9 and Bax upregulated while that of Bcl-2 downregulated.BJO suppressed the PI3K/AKT pathway and promoted phosphorylation of adenosine monophosphate-activated protein kinase,while repressing the phosphorylation of mechanistic target of rapamycin.Compared with treatment by BJO alone,the PI3K/AKT agonist 740Y-P increased the survival rate of HepG2 cells(P<0.01)and attenuated the inhibitory effect of BJO on cell apoptosis(P<0.05).Conclusion:BJO is capable of inhibiting proliferation of HepG2 cells and inducing apoptosis via the PI3K/AKT pathway.展开更多
ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Tradition...ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval method were applied to obtain the active ingredients of Yadanzi(Brucea javanica),and to predict the relevant targets of the active ingredients.The GBM-related targets were retrieved and screened through the Gene Expression Profling Interactive Analysis(GEPIA)database,and mapped to each other with the targets of the components of Yadanzi(Brucea javanica)to obtain the intersection targets.The GBM differentially expressed gene targets were imported into the String database to obtain the protein interaction relationship,the Cytoscape software was used to draw the protein interaction network,the Cytobba and MCODE plug-ins were used to screen the core genes and important protein interaction modules,and the GEPIA database was applied to make survival analysis of the core genes.The network map of“active ingredients-targets”was constructed through the Cytoscape 3.6.1 software.Gene Ontology(GO)biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for GBM differentially expressed genes were performed through the DAVID database.ResultsThrough TCMSP and literature retrieval,23 potential active ingredients and 129 related targets were obtained from Yadanzi(Brucea javanica).In the GEPIA database,247 GBM differentially expressed genes were screened,including 113 upregulated genes and 134 downregulated genes.After mapping with the targets related to the active ingredients of Yadanzi(Brucea javanica),six intersection targets were obtained,that is,the potential action targets of Yadanzi(Brucea javanica)in treating GBM,including MMP2,HMOX1,BIRC5,EGFR,CCNB2,and TOP2A.Cytoscape software was applied to build an“active ingredient-action target”network.Two active ingredients and five action targets of β-sitosterol(BS)and luteolin were found,and the targets were mainly concentrated in BS.It was found by KEGG pathway enrichment analysis that GBM differentially expressed genes were mainly involved in signaling pathways related to Staphylococcus aureus infection,phagosome formation,tuberculosis and systemic lupus erythematosus and other infectious and autoimmune diseases.It was found by GO enrichment analysis that the GBM differentially expressed genes mainly involved such biological processes(BP)as the processing and presentation of exogenous antigenic peptides and polysaccharide antigens through MHC Il molecules,y-interferon-mediated signaling pathways,extracellular matrix composition,and chemical synapses transmission;it involved cellular components such as cell junctions,axon terminal buttons,extracellular space,vesicle membranes for endocytosis,and MHC Il protein complexes;molecular functions such as calcium-mediated ionic protein binding,MHC Il molecular receptor activity,immunoglobulin binding,and phospholipase inhibitor activity were also involved.Survival analysis was conducted by GEPIA on the top 37 core targets in degree value,and a total of five genes related to GBM prognosis were obtained.Among them,FN1 and MMP2 were highly expressed while GABRD(v-aminobutyric acid A receptor delta subunit),RBFOX1,and SLC6A7 were expressed at a low level in cancer patients.Conclusion The pathogenesis of GBM is closely related to the human immune system,and BS and luteolin may be the main material basis of Yadanzi(Brucea javanica)for the treatment of GBM and the improvement of prognosis.The molecular mechanism may be related to the physical barrier formed by destroying the tumor cell stromal 68 Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology Zhao,Si.molecules and its involvement in tumor immune response.展开更多
BACKGROUND Esophageal cancer is one of the most common cancers around the world, and it has high incidence and mortality rates. The conventional therapy for esophageal cancer is radiotherapy, although its effect is hi...BACKGROUND Esophageal cancer is one of the most common cancers around the world, and it has high incidence and mortality rates. The conventional therapy for esophageal cancer is radiotherapy, although its effect is highly limited by the resistance of esophageal cancer cells. Thus, strong radiosensitizers can be very crucial during radiotherapy against esophageal cancer. Brucea javanica oil emulsion (BJOE) is a widely used drug against various cancers, such as liver, colon, and ovarian cancer. However, its anti-cancer effect and mechanism and the use of BJOE as a radiosensitizer have not been explored in esophageal cancer. AIM To evaluate the anti-cancer effect and mechanism of BJOE and explore the potential use of BJOE as a radiosensitizer during radiotherapy. METHODS The inhibitory effect of BJOE and its enhancement function with radiation on cell viability were examined with the calculated half-maximal effective concentration and half-maximal lethal concentration. The influence of BJOE on cell migration and invasion were measured with EC109 and JAR cells by wound-healing and transwell assay. Clonogenesis and apoptotic rate, which was measured by Hoechst staining, were investigated to confirm its enhancement function with radiation. To investigate the molecular pathway underlying the effect of BJOE, the expressions of several apoptosis- and cycle-related proteins was detected by western blotting.cell lines more than normal cell lines, and it markedly reduced migration and invasion in esophageal cancer cells (EC109 and JAR). Moreover, it promoted cell apoptosis and enhanced the effect of radiotherapy against esophageal cancerous cells. In the viability test, the values of half-maximal effective concentration and half-maximal lethal concentration were reduced. Compared to the control, only around 1/5 colonies formed when using BJOE and radiation together in the clonogenic assay. The apoptotic rate in EC109 was obviously promoted when BJOE was added during radiotherapy. Our study suggests that the expression of the apoptosis-proteins Bax and p21 were increased, while the expression of Bcl-2 was stable. Further detection of downstream proteins revealed that the expression of cyclin D1 and cyclin-dependent kinase 4/6 were significantly decreased. CONCLUSION BJOE has a strong anti-cancer effect on esophageal cancer and can be used as a radiosensitizer to promote apoptosis in cancerous esophageal cells via the cyclin D1-cyclin-dependent kinase 4/6 axis.展开更多
The present study aims to investigate the gastroprotective effect of Brucea javanica oil emulsion(BJOE) in animals. Gastroprotective potential of BJOE was studied on absolute ethanol,aspirin, reserpine and restraint p...The present study aims to investigate the gastroprotective effect of Brucea javanica oil emulsion(BJOE) in animals. Gastroprotective potential of BJOE was studied on absolute ethanol,aspirin, reserpine and restraint plus water immersion-induced gastric ulcers in mice as well as glacial acetic acid(GAA) and pyloric ligation(PL)-induced gastric ulcers in rats. Except for ulcer scores, total acidity as well as pepsin activity as for the PL-induced gastric ulcer model and ulcer incidence as for the GAA-induced gastric ulcer model were also determined. Histopathological evaluation as for aspirin, reserpine, PL-induced models was conducted. Results showed that BJOE significantly(P < 0.05) reduced ulcer index in the mouse and rat models in a dose-dependent manner. It had significant(P < 0.05) suppressive effect on total activity of gastric juice as well in PL-induced model. Histopathological examination for the stomach samples confirmed the findings in the aspirin, reserpine or PLinduced gastric lesion models, which showed relatively complete mucosa structure and less inflammation. It is concluded that BJOE could be effective on gastric ulcer in rodents and its gastroprotective activity might be related to antioxidant, anti-inflammatory ability and promote gastric mucus secreted. The results may provide beneficial basis for increasing BJOE's clinical indication in future.展开更多
Objective This study engaged in investigation of optimal formulation,characteristics analysis of Brucea javanica oil microemulsion(BJOM) in order to address safety concerns and make recommendations for improvements in...Objective This study engaged in investigation of optimal formulation,characteristics analysis of Brucea javanica oil microemulsion(BJOM) in order to address safety concerns and make recommendations for improvements in BJOM safety during clinical use in vivo.Methods Pseudo-ternary phase diagram techniques were used to determine the appropriate ratio of surfactant,cosurfactant,and oil phases.Subsequent stability testing of BJOM was performed by dilution,centrifugation,and accelerated stability testing.The results were expounded through additional assessment utilizing the classical thermostat method to establish the shelf life of the material.These results were utilized to evaluate the safety of BJOM by haemolytic,irritative and allergic testing in vitro.In addition,the cytotoxicity of BJOM was examined using the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide(MTT),with particular emphasis given to potential uses in cancer treatment.Results The most suitable method of preparation for BJOM was found to be a one to one ratio(Km 1∶ 1) of Solutol HS15 surfactant matched with sorbitol cosurfactant in the ratio.The microemulsion droplets of BJOM possessed a spherical shape,uniform size,and average diameter of 23.8nm.The expiration date of BJOM was found to be 568d.The safety study demonstrated no haemolysis activity at the experimental BJOM concentrations;however,mild haemolysis was observed at higher concentrations of Brucea javanica oil emulsion(BJOE),a common commercially available product.Irritation observed upon BIOM treatment can be primarily attributed to Brucea javanica oil(BJO) with little influence of BJOM excipients.In addition,BJOM caused no observed hypersensitivity or other visible allergic reactions in guinea pigs.The anticancer activity curves of BJOM and BJOE demonstrate that both BJOM and BJOE inhibit Hela cells,with BIOM demonstrating significantly more dramatic anticancer activity.Conclusion An optimal formulation of BJOM superior to commercially available products and safe for medical application such as intravenous injection has been outlined along with its anticancer activity rating.展开更多
Brusatol,a triterpene lactone compound mainly from Brucea javanica,sensitizes a broad spectrum of cancer cells.It is known as a specific inhibitor of nuclear factor-erythroid 2-related factor 2(Nrf2)pathway.In this re...Brusatol,a triterpene lactone compound mainly from Brucea javanica,sensitizes a broad spectrum of cancer cells.It is known as a specific inhibitor of nuclear factor-erythroid 2-related factor 2(Nrf2)pathway.In this review,we provide a comprehensive overview on the antitumor effect and molecular mechanisms of brusatol in vitro and in vivo.This review also covers pharmacokinetics studies,modification of dosages forms of brusatol.Increasing evidences have validated the value of brusatol as a chemotherapeutic agent in cancers,which may contribute to drug development and clinical application.展开更多
Objective: Developed the core-matched nanoemulsions(CMNEs) to co-delivery paclitaxel-oleic acid(PTXOA) prodrug and Brucea javanica oil(BJO) for increasing the antitumor effect.Methods: Antitumor effects and mechanism ...Objective: Developed the core-matched nanoemulsions(CMNEs) to co-delivery paclitaxel-oleic acid(PTXOA) prodrug and Brucea javanica oil(BJO) for increasing the antitumor effect.Methods: Antitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy which based on core-matched technology(CMT) were evaluated in vitro and in vivo.Results: The PTX-OA/BJO CMNEs were of nanoscale particle size(108.7 ± 2.3) nm and with entrapment efficiency of >95%. The PTX-OA/BJO CMNEs displayed concentration and time-dependent cytotoxicity against HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of the tumor volume with no obvious toxicity was observed in nude mice model following administration of PTX-OA/BJO CMNEs compared with the control treated with normal saline(P < 0.05), which suggested the excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEs were associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibiting tumor cell proliferation and the activity of TOPOⅡ.Conclusion: Co-encapsulation of two drugs with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity.展开更多
Brucea javanica, a Chinese herbal medicine, combined with conventional anticancer modalities, has been widely used for treatment of various cancers. Based on researches over the last decades, authors briefly summarize...Brucea javanica, a Chinese herbal medicine, combined with conventional anticancer modalities, has been widely used for treatment of various cancers. Based on researches over the last decades, authors briefly summarized its active constituents, molecular mechanisms and clinical application for cancer treatment.展开更多
In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation ef...In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box–Behnken design consisted of 1.7% alginate(W/V), 1.02% carrageenan(W/V), 1.4% CaCO_3(W/V), and a gelling bath of pH 0.8. The alginate–carrageenan–Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%–55% and an encapsulation efficiency of 70%–80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention(> 60% at 6 h) in fasted rats, compared to non-floating beads(15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography(SPET/CT). In conclusion, the alginate–carrageenan–Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.展开更多
Brucea javanica oil emulsion(BJOE)has been used to treat tumor in China for more than 40 years.However,its components and effectiveness in the treatment of acute lymphocytic leukemia(ALL)and its mechanism of anti-canc...Brucea javanica oil emulsion(BJOE)has been used to treat tumor in China for more than 40 years.However,its components and effectiveness in the treatment of acute lymphocytic leukemia(ALL)and its mechanism of anti-cancer activity remain unknown.In the current study,high-performance liquid chromatography-evaporative light scattering detector(HPLC-ELSD)was used to analyze the components of BJOE.Then,the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model,respectively.The primary ALL leukemia cells were also used to confirm the antileukemia effects of BJOE.The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction.Moreover,BJOE inhibited Akt(protein kinase B)activation and upregulated its downstream targets p53 and Fox O1(forkhead box gene,group O-1)to initiate apoptosis.The activation of GSK3βwas also involved.Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase(PI3 K)/Akt signaling pathway.展开更多
Aim:Therapy to overcome drug resistance by modulating epidermal growth factor receptor(EGFR)is a viable approach to suppress the proliferation of human non-small cell lung cancer(NSCLC)cells.A previous study demonstra...Aim:Therapy to overcome drug resistance by modulating epidermal growth factor receptor(EGFR)is a viable approach to suppress the proliferation of human non-small cell lung cancer(NSCLC)cells.A previous study demonstrated that the seeds of an aqueous Brucea javanica(BJ)(L.)Merr(Simaroubaceae)extract containing quassinoid mixtures effectively inhibited the growth and alleviated tumorigenesis in H1975 cells of NSCLC by targeting T790M/L858R EGFR.This study aimed to further determine whether the aqueous BJ extract affects the enriched H1975 spheroids in suspension culture and mouse xenograft tumor models.Methods:The spheroids of NSCLC adenocarcinoma H1975 cells were enriched in a serum-free media.The growth rate of sphere propagation by aqueous BJ extract was determined in suspended culture and in colony-formation assay.BJ extract was fed orally to nude mice bearing xenograft tumors.The resected tumors were analyzed by hematoxylin and eosin staining,terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay,and proliferating cell nuclear antigen assessment.Various markers were used to determine the pluripotency of tumors from mice treated with different concentrations of BJ extract.Results:BJ extract was demonstrated to be effective against the propagation of the enriched spheroids.In animal models,oral administration of the aqueous BJ extract reduced spheroid tumorigenicity.The alleviated growth of the established xenograft tumors can be attributed to the reduced drug resistance and induced apoptosis without distinct adverse effects.More evidence supports activated apoptotic death attenuated spheroid stemness of tumors.Conclusion:As an effective treatment regime to assuage lung cancer,the indigenous BJ extract promises to obliterate drug resistance and the growth of cancer stem cell tumors from NSCLC cells harboring T790M/L858R EGFR.展开更多
Background: Malignant pleural effusion (MPE) is the most common complication of advanced NSCLC. Infusion chemotherapy is currently one of the most common intracavitary treatments for MPE. Unfortunately, there is no de...Background: Malignant pleural effusion (MPE) is the most common complication of advanced NSCLC. Infusion chemotherapy is currently one of the most common intracavitary treatments for MPE. Unfortunately, there is no definitive consensus on which intracavitary infusion drug has the best effect on the treatment. The use of de-platinum-based thoracic perfusion therapy can offer several advantages, such as reducing drug toxicity and contributing to an improvement in patients’ physical condition. Therefore, this study was to investigate the clinical efficacy and safety of de-platinum-based pleural perfusion bevacizumab combined with Brucea Javanica Oil Emulsion Injection (BJOEI) in the treatment of malignant pleural effusion in advanced lung adenocarcinoma. Methods: A total of 60 patients diagnosed with lung adenocarcinoma and malignant pleural effusion were selected from Binzhou People’s Hospital, Shandong Provincial Cancer Hospital, and Binzhou Central Hospital between June 2022 and May 2024, with 30 cases treated in each group. The study was divided into two groups: the treatment group received bevacizumab injection perfusion in combination with intravenous infusion of Brucea Javanica Oil Emulsion Injection (BJOEI), while the control group received bevacizumab injection combined with cisplatin perfusion. To analyze the data and evaluate their efficacy and adverse reactions, such as disease control rate (DCR), overall response rate (ORR), Karnofsky Performance Status (KPS), vascular endothelial growth factor (VEGF), and so forth. Results: Following the treatment, the quality of life scores in both groups exhibited an increase compared to pre-treatment levels. Moreover, the enhancement observed in the treatment group was deemed statistically significant (P = 0.007). Following treatment, The expression of VEGF in the pleural effusion of both groups of patients was significantly decreased, and the disparity within the same group was found to be statistically significant (P P χ2 = 0.317, P = 0.573;χ2 = 0.218, P = 0.640). A stratified analysis of factors influencing the ORR revealed that the ORR in both groups exhibited statistical significance when the previous KPS score was below 70 (χ2 = 5.850, P = 0.016). The main adverse reactions in both groups included nausea, vomiting, gastrointestinal reactions, fatigue, and hematological toxicity. Among them, there was a statistically significant difference in the occurrence of gastrointestinal reactions and fatigue between the two groups (χ2 = 8.148, P = 0.004;χ2 = 6.696, P = 0.010). Conclusion: Bevacizumab, when combined with Brucea Javanica Oil Emulsion Injection (BJOEI), demonstrates noteworthy efficacy in treating malignant pleural effusion. This combination therapy reduces VEGF expression, in which the reduction supports the efficacy of thoracic perfusion and is associated with minimal adverse reactions, contributing to an improvement in patients’ physical condition and overall clinical tolerability, especially for the poor physique, especially in the elderly and KPS score is less than 70. Therefore, it can be considered a recommended approach for managing malignant pleural effusion, offering significant clinical value.展开更多
基金Supported by Guangxi Science Foundation(0639027)Science and Technology Developmental Fund of Guangxi Academy of Agricultural Sciences(2006025)~~
文摘[Objective] The research aimed to lay a foundation for the screening of cell lines producing secondary metabolites of Brucea javanica(L.)Merr.[Method] The insecticidal activities of the extracts from branch and 3 different types of calluses of Brucea javanica(L.)Merr.was detected through methods of leaf disc and potted seedlings against the diamond back moth.[Result] Extracts from four kinds of Brucea javanica(L.)Merr.tissues assumed both the activities of antifeedant and oviposition deterrency against the diamond back moth.Antifeedant effect of extracts was in turn the callus C< callus B< callus A< branches.Oviposition deterrency activity of the extracts was in turn the callus A> branch > callus B>callus C.The insecticidal activities of callus A and B were higher than that of the callus C.[Conclusion] The results show that insecticidal activity of callus and its growth rate is inversely proportional.
基金This experiment was supported by the National Natural Science Foundation of China(No.81872972).
文摘Objective:The morbidity of malignant melanoma keeps increasing annually.It has high risks of metastasis,drug resistance,and poor prognosis in clinics.Moreover,the available medicines used commonly,such as dacarbazine,temozolomide,the v-Raf murine sarcoma viral oncogene homolog B1(BRAF)inhibitor vemurafenib,and the programmed cell death protein 1 inhibitor pembrolizumab,have some limitations at some extent.Therefore,a more effective therapeutic strategy is still urgently necessary.Methods:In this study,Brucea javanica(L.)Merr.globulins were hydrolyzed with pepsin,then ultra-filtrated to collect small molecular peptides(≤3 kDa).The peptides were then analyzed by antiproliferative assay,cell-cycle distribution,apoptosis assay,and in vitro wound-scratch assay.Finally,western blotting was conducted to elucidate the underlying anti-melanoma mechanism.Results:The small molecular peptide from B.javanica significantly inhibited malignant melanoma cell proliferation with the IC_(50) of 2.72 mg/mL for 72 h.Further analysis indicated that B.javanica peptides arrested cell cycle at the S and G2/M phases and induced apoptosis by upregulating p21,p53,Bax,caspase-3,and cleaved PARP while downregulating Bcl-2 expression.The inhibitory migration effects were also confirmed by wound-healing assay.Conclusion:The small molecular biopeptides from B.javanica may be a promising bioactive agent candidate for melanoma treatment.
基金This study was supported by The National Science Foundation of China(31671786)the National Key R&D Program of China(2016YFD0401404).
文摘Background:Brucea javanica oil(BJO),distributed primarily in Southeast Asia,has long been utilized as a therapeutic agent for treating malignancies.However,its anticancer mechanisms are not clearly understood.The objective of this study was to examine the mechanisms underlying its treatment of hepatocellular carcinoma cells.Methods:CCK8 assay was used to evaluate cell viability.Hoechst33342 staining and flow cytometry analyses were used to examine apoptosis.Mito-Tracker Red CMXRos kit was used to measure the membrane potential of mitochondria.ATP assay kit was used to evaluate ATP levels.Western blots were used to assess the presence of AKT,adenosine monophosphate-activated protein kinase,Caspase3,Caspase9,Bax,and Bcl-2.Results:BJO inhibited the proliferation of hepatocellular carcinoma cells HepG2 in a time-and dose-dependent manner.It induced apoptosis,with the percentage of cells treated with 50–150μg/mL BJO increasing from 8.01%to 28.02%in a concentration-dependent manner(P<0.05,when 50μg/mL of BJO group compared with the control group;P<0.001,when 100 or 150μg/mL of BJO group compared with the control group).After exposed to BJO,the expression of C-caspase3,C-caspase9 and Bax upregulated while that of Bcl-2 downregulated.BJO suppressed the PI3K/AKT pathway and promoted phosphorylation of adenosine monophosphate-activated protein kinase,while repressing the phosphorylation of mechanistic target of rapamycin.Compared with treatment by BJO alone,the PI3K/AKT agonist 740Y-P increased the survival rate of HepG2 cells(P<0.01)and attenuated the inhibitory effect of BJO on cell apoptosis(P<0.05).Conclusion:BJO is capable of inhibiting proliferation of HepG2 cells and inducing apoptosis via the PI3K/AKT pathway.
文摘ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval method were applied to obtain the active ingredients of Yadanzi(Brucea javanica),and to predict the relevant targets of the active ingredients.The GBM-related targets were retrieved and screened through the Gene Expression Profling Interactive Analysis(GEPIA)database,and mapped to each other with the targets of the components of Yadanzi(Brucea javanica)to obtain the intersection targets.The GBM differentially expressed gene targets were imported into the String database to obtain the protein interaction relationship,the Cytoscape software was used to draw the protein interaction network,the Cytobba and MCODE plug-ins were used to screen the core genes and important protein interaction modules,and the GEPIA database was applied to make survival analysis of the core genes.The network map of“active ingredients-targets”was constructed through the Cytoscape 3.6.1 software.Gene Ontology(GO)biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for GBM differentially expressed genes were performed through the DAVID database.ResultsThrough TCMSP and literature retrieval,23 potential active ingredients and 129 related targets were obtained from Yadanzi(Brucea javanica).In the GEPIA database,247 GBM differentially expressed genes were screened,including 113 upregulated genes and 134 downregulated genes.After mapping with the targets related to the active ingredients of Yadanzi(Brucea javanica),six intersection targets were obtained,that is,the potential action targets of Yadanzi(Brucea javanica)in treating GBM,including MMP2,HMOX1,BIRC5,EGFR,CCNB2,and TOP2A.Cytoscape software was applied to build an“active ingredient-action target”network.Two active ingredients and five action targets of β-sitosterol(BS)and luteolin were found,and the targets were mainly concentrated in BS.It was found by KEGG pathway enrichment analysis that GBM differentially expressed genes were mainly involved in signaling pathways related to Staphylococcus aureus infection,phagosome formation,tuberculosis and systemic lupus erythematosus and other infectious and autoimmune diseases.It was found by GO enrichment analysis that the GBM differentially expressed genes mainly involved such biological processes(BP)as the processing and presentation of exogenous antigenic peptides and polysaccharide antigens through MHC Il molecules,y-interferon-mediated signaling pathways,extracellular matrix composition,and chemical synapses transmission;it involved cellular components such as cell junctions,axon terminal buttons,extracellular space,vesicle membranes for endocytosis,and MHC Il protein complexes;molecular functions such as calcium-mediated ionic protein binding,MHC Il molecular receptor activity,immunoglobulin binding,and phospholipase inhibitor activity were also involved.Survival analysis was conducted by GEPIA on the top 37 core targets in degree value,and a total of five genes related to GBM prognosis were obtained.Among them,FN1 and MMP2 were highly expressed while GABRD(v-aminobutyric acid A receptor delta subunit),RBFOX1,and SLC6A7 were expressed at a low level in cancer patients.Conclusion The pathogenesis of GBM is closely related to the human immune system,and BS and luteolin may be the main material basis of Yadanzi(Brucea javanica)for the treatment of GBM and the improvement of prognosis.The molecular mechanism may be related to the physical barrier formed by destroying the tumor cell stromal 68 Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology Zhao,Si.molecules and its involvement in tumor immune response.
文摘BACKGROUND Esophageal cancer is one of the most common cancers around the world, and it has high incidence and mortality rates. The conventional therapy for esophageal cancer is radiotherapy, although its effect is highly limited by the resistance of esophageal cancer cells. Thus, strong radiosensitizers can be very crucial during radiotherapy against esophageal cancer. Brucea javanica oil emulsion (BJOE) is a widely used drug against various cancers, such as liver, colon, and ovarian cancer. However, its anti-cancer effect and mechanism and the use of BJOE as a radiosensitizer have not been explored in esophageal cancer. AIM To evaluate the anti-cancer effect and mechanism of BJOE and explore the potential use of BJOE as a radiosensitizer during radiotherapy. METHODS The inhibitory effect of BJOE and its enhancement function with radiation on cell viability were examined with the calculated half-maximal effective concentration and half-maximal lethal concentration. The influence of BJOE on cell migration and invasion were measured with EC109 and JAR cells by wound-healing and transwell assay. Clonogenesis and apoptotic rate, which was measured by Hoechst staining, were investigated to confirm its enhancement function with radiation. To investigate the molecular pathway underlying the effect of BJOE, the expressions of several apoptosis- and cycle-related proteins was detected by western blotting.cell lines more than normal cell lines, and it markedly reduced migration and invasion in esophageal cancer cells (EC109 and JAR). Moreover, it promoted cell apoptosis and enhanced the effect of radiotherapy against esophageal cancerous cells. In the viability test, the values of half-maximal effective concentration and half-maximal lethal concentration were reduced. Compared to the control, only around 1/5 colonies formed when using BJOE and radiation together in the clonogenic assay. The apoptotic rate in EC109 was obviously promoted when BJOE was added during radiotherapy. Our study suggests that the expression of the apoptosis-proteins Bax and p21 were increased, while the expression of Bcl-2 was stable. Further detection of downstream proteins revealed that the expression of cyclin D1 and cyclin-dependent kinase 4/6 were significantly decreased. CONCLUSION BJOE has a strong anti-cancer effect on esophageal cancer and can be used as a radiosensitizer to promote apoptosis in cancerous esophageal cells via the cyclin D1-cyclin-dependent kinase 4/6 axis.
文摘The present study aims to investigate the gastroprotective effect of Brucea javanica oil emulsion(BJOE) in animals. Gastroprotective potential of BJOE was studied on absolute ethanol,aspirin, reserpine and restraint plus water immersion-induced gastric ulcers in mice as well as glacial acetic acid(GAA) and pyloric ligation(PL)-induced gastric ulcers in rats. Except for ulcer scores, total acidity as well as pepsin activity as for the PL-induced gastric ulcer model and ulcer incidence as for the GAA-induced gastric ulcer model were also determined. Histopathological evaluation as for aspirin, reserpine, PL-induced models was conducted. Results showed that BJOE significantly(P < 0.05) reduced ulcer index in the mouse and rat models in a dose-dependent manner. It had significant(P < 0.05) suppressive effect on total activity of gastric juice as well in PL-induced model. Histopathological examination for the stomach samples confirmed the findings in the aspirin, reserpine or PLinduced gastric lesion models, which showed relatively complete mucosa structure and less inflammation. It is concluded that BJOE could be effective on gastric ulcer in rodents and its gastroprotective activity might be related to antioxidant, anti-inflammatory ability and promote gastric mucus secreted. The results may provide beneficial basis for increasing BJOE's clinical indication in future.
文摘Objective This study engaged in investigation of optimal formulation,characteristics analysis of Brucea javanica oil microemulsion(BJOM) in order to address safety concerns and make recommendations for improvements in BJOM safety during clinical use in vivo.Methods Pseudo-ternary phase diagram techniques were used to determine the appropriate ratio of surfactant,cosurfactant,and oil phases.Subsequent stability testing of BJOM was performed by dilution,centrifugation,and accelerated stability testing.The results were expounded through additional assessment utilizing the classical thermostat method to establish the shelf life of the material.These results were utilized to evaluate the safety of BJOM by haemolytic,irritative and allergic testing in vitro.In addition,the cytotoxicity of BJOM was examined using the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide(MTT),with particular emphasis given to potential uses in cancer treatment.Results The most suitable method of preparation for BJOM was found to be a one to one ratio(Km 1∶ 1) of Solutol HS15 surfactant matched with sorbitol cosurfactant in the ratio.The microemulsion droplets of BJOM possessed a spherical shape,uniform size,and average diameter of 23.8nm.The expiration date of BJOM was found to be 568d.The safety study demonstrated no haemolysis activity at the experimental BJOM concentrations;however,mild haemolysis was observed at higher concentrations of Brucea javanica oil emulsion(BJOE),a common commercially available product.Irritation observed upon BIOM treatment can be primarily attributed to Brucea javanica oil(BJO) with little influence of BJOM excipients.In addition,BJOM caused no observed hypersensitivity or other visible allergic reactions in guinea pigs.The anticancer activity curves of BJOM and BJOE demonstrate that both BJOM and BJOE inhibit Hela cells,with BIOM demonstrating significantly more dramatic anticancer activity.Conclusion An optimal formulation of BJOM superior to commercially available products and safe for medical application such as intravenous injection has been outlined along with its anticancer activity rating.
基金supported by National Natural Science Foundation of China(81872767)。
文摘Brusatol,a triterpene lactone compound mainly from Brucea javanica,sensitizes a broad spectrum of cancer cells.It is known as a specific inhibitor of nuclear factor-erythroid 2-related factor 2(Nrf2)pathway.In this review,we provide a comprehensive overview on the antitumor effect and molecular mechanisms of brusatol in vitro and in vivo.This review also covers pharmacokinetics studies,modification of dosages forms of brusatol.Increasing evidences have validated the value of brusatol as a chemotherapeutic agent in cancers,which may contribute to drug development and clinical application.
基金supported by the National Natural Science Foundation of China(81403109)Science and Technology Planning Project of Guangdong Province(2014A020210021,2016A020217017)
文摘Objective: Developed the core-matched nanoemulsions(CMNEs) to co-delivery paclitaxel-oleic acid(PTXOA) prodrug and Brucea javanica oil(BJO) for increasing the antitumor effect.Methods: Antitumor effects and mechanism of PTX-OA/BJO CMNEs that the combination therapy which based on core-matched technology(CMT) were evaluated in vitro and in vivo.Results: The PTX-OA/BJO CMNEs were of nanoscale particle size(108.7 ± 2.3) nm and with entrapment efficiency of >95%. The PTX-OA/BJO CMNEs displayed concentration and time-dependent cytotoxicity against HepG-2 cells and increased G2/M phase block. More importantly, a significant reduction of the tumor volume with no obvious toxicity was observed in nude mice model following administration of PTX-OA/BJO CMNEs compared with the control treated with normal saline(P < 0.05), which suggested the excellent efficacy in vivo. It was further found that the enhanced effectiveness of PTX-OA/BJO CMNEs were associated with the ability of inducing apoptosis of the tumor cells, as well as obviously inhibiting tumor cell proliferation and the activity of TOPOⅡ.Conclusion: Co-encapsulation of two drugs with different mechanisms allows simultaneous interruption of diverse anticancer pathways, resulting in increased therapeutic response and lower toxicity.
基金Supported by Grants from Administration of Traditional Chinese Medicine of Guangdong Province,China(No.20111169)
文摘Brucea javanica, a Chinese herbal medicine, combined with conventional anticancer modalities, has been widely used for treatment of various cancers. Based on researches over the last decades, authors briefly summarized its active constituents, molecular mechanisms and clinical application for cancer treatment.
基金supported by the National Natural Science Foundation of China(No.81303233)Foundation of Shanghai Science and Technology Committee(No.13401900300)Shanghai Municipal Commission of Health and Family Planning(No.20124074)
文摘In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box–Behnken design consisted of 1.7% alginate(W/V), 1.02% carrageenan(W/V), 1.4% CaCO_3(W/V), and a gelling bath of pH 0.8. The alginate–carrageenan–Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%–55% and an encapsulation efficiency of 70%–80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention(> 60% at 6 h) in fasted rats, compared to non-floating beads(15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography(SPET/CT). In conclusion, the alginate–carrageenan–Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.
基金supported by the Young Scientific and Technological Talents Seeding Program of Liaoning Education Office(No.2019LQN10)Shenyang Young and Middle-Aged Science and Technology Innovation Program(No.RC180308)。
文摘Brucea javanica oil emulsion(BJOE)has been used to treat tumor in China for more than 40 years.However,its components and effectiveness in the treatment of acute lymphocytic leukemia(ALL)and its mechanism of anti-cancer activity remain unknown.In the current study,high-performance liquid chromatography-evaporative light scattering detector(HPLC-ELSD)was used to analyze the components of BJOE.Then,the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model,respectively.The primary ALL leukemia cells were also used to confirm the antileukemia effects of BJOE.The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction.Moreover,BJOE inhibited Akt(protein kinase B)activation and upregulated its downstream targets p53 and Fox O1(forkhead box gene,group O-1)to initiate apoptosis.The activation of GSK3βwas also involved.Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase(PI3 K)/Akt signaling pathway.
基金The work is supported by grants from Ministry of Science and Technology,Executive Yuan,ROC(MOST 104-2320-B-003-001)National Taiwan Normal University(103T3040D2 and 104T3040C2).
文摘Aim:Therapy to overcome drug resistance by modulating epidermal growth factor receptor(EGFR)is a viable approach to suppress the proliferation of human non-small cell lung cancer(NSCLC)cells.A previous study demonstrated that the seeds of an aqueous Brucea javanica(BJ)(L.)Merr(Simaroubaceae)extract containing quassinoid mixtures effectively inhibited the growth and alleviated tumorigenesis in H1975 cells of NSCLC by targeting T790M/L858R EGFR.This study aimed to further determine whether the aqueous BJ extract affects the enriched H1975 spheroids in suspension culture and mouse xenograft tumor models.Methods:The spheroids of NSCLC adenocarcinoma H1975 cells were enriched in a serum-free media.The growth rate of sphere propagation by aqueous BJ extract was determined in suspended culture and in colony-formation assay.BJ extract was fed orally to nude mice bearing xenograft tumors.The resected tumors were analyzed by hematoxylin and eosin staining,terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay,and proliferating cell nuclear antigen assessment.Various markers were used to determine the pluripotency of tumors from mice treated with different concentrations of BJ extract.Results:BJ extract was demonstrated to be effective against the propagation of the enriched spheroids.In animal models,oral administration of the aqueous BJ extract reduced spheroid tumorigenicity.The alleviated growth of the established xenograft tumors can be attributed to the reduced drug resistance and induced apoptosis without distinct adverse effects.More evidence supports activated apoptotic death attenuated spheroid stemness of tumors.Conclusion:As an effective treatment regime to assuage lung cancer,the indigenous BJ extract promises to obliterate drug resistance and the growth of cancer stem cell tumors from NSCLC cells harboring T790M/L858R EGFR.
文摘Background: Malignant pleural effusion (MPE) is the most common complication of advanced NSCLC. Infusion chemotherapy is currently one of the most common intracavitary treatments for MPE. Unfortunately, there is no definitive consensus on which intracavitary infusion drug has the best effect on the treatment. The use of de-platinum-based thoracic perfusion therapy can offer several advantages, such as reducing drug toxicity and contributing to an improvement in patients’ physical condition. Therefore, this study was to investigate the clinical efficacy and safety of de-platinum-based pleural perfusion bevacizumab combined with Brucea Javanica Oil Emulsion Injection (BJOEI) in the treatment of malignant pleural effusion in advanced lung adenocarcinoma. Methods: A total of 60 patients diagnosed with lung adenocarcinoma and malignant pleural effusion were selected from Binzhou People’s Hospital, Shandong Provincial Cancer Hospital, and Binzhou Central Hospital between June 2022 and May 2024, with 30 cases treated in each group. The study was divided into two groups: the treatment group received bevacizumab injection perfusion in combination with intravenous infusion of Brucea Javanica Oil Emulsion Injection (BJOEI), while the control group received bevacizumab injection combined with cisplatin perfusion. To analyze the data and evaluate their efficacy and adverse reactions, such as disease control rate (DCR), overall response rate (ORR), Karnofsky Performance Status (KPS), vascular endothelial growth factor (VEGF), and so forth. Results: Following the treatment, the quality of life scores in both groups exhibited an increase compared to pre-treatment levels. Moreover, the enhancement observed in the treatment group was deemed statistically significant (P = 0.007). Following treatment, The expression of VEGF in the pleural effusion of both groups of patients was significantly decreased, and the disparity within the same group was found to be statistically significant (P P χ2 = 0.317, P = 0.573;χ2 = 0.218, P = 0.640). A stratified analysis of factors influencing the ORR revealed that the ORR in both groups exhibited statistical significance when the previous KPS score was below 70 (χ2 = 5.850, P = 0.016). The main adverse reactions in both groups included nausea, vomiting, gastrointestinal reactions, fatigue, and hematological toxicity. Among them, there was a statistically significant difference in the occurrence of gastrointestinal reactions and fatigue between the two groups (χ2 = 8.148, P = 0.004;χ2 = 6.696, P = 0.010). Conclusion: Bevacizumab, when combined with Brucea Javanica Oil Emulsion Injection (BJOEI), demonstrates noteworthy efficacy in treating malignant pleural effusion. This combination therapy reduces VEGF expression, in which the reduction supports the efficacy of thoracic perfusion and is associated with minimal adverse reactions, contributing to an improvement in patients’ physical condition and overall clinical tolerability, especially for the poor physique, especially in the elderly and KPS score is less than 70. Therefore, it can be considered a recommended approach for managing malignant pleural effusion, offering significant clinical value.
