Insecticidal Activities of Extracts from Brucea javanica (L.) Merr. Callus

[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.

Brucea javanica oil emulsion improves the effect of radiotherapy on esophageal cancer cells by inhibiting cyclin D1-CDK4/6 axis

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.

Pretreated Oenan the Javanica extract increases anti-inflammatory cytokines, attenuates gliosis, and protects hippocampal neurons following transient global cerebral ischemia in gerbils

Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.

Activity of Brucea javanica oil emulsion against gastric ulcers in rodents

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.

Ethanol extract of Oenanthe javanica increases cell proliferation and neuroblast differentiation in the adolescent rat dentate gyrus

Oenanthe javanica is an aquatic perennial herb that belongs to theOenanthe genus in Apiaceae family, and it displays well-known medicinal properties such as protective effects against glu-tamate-induced neurotoxicity. However, few studies regarding effects ofOenanthe javanica on neurogenesis in the brain have been reported. In this study, we examined the effects of a normal diet and a diet containing ethanol extract ofOenanthe javanica on cell proliferation and neu-roblast differentiation in the subgranular zone of the hippocampal dentate gyrus of adolescent rats using Ki-67 （an endogenous marker for cell proliferation） and doublecortin （a marker for neuroblast）. Our results showed thatOenanthe javanica extract signiifcantly increased the number of Ki-67-immunoreactive cells and doublecortin-immunoreactive neuroblasts in the subgranular zone of the dentate gyrus in the adolescent rats. In addition, the immunoreactivity of brain-derived neurotrophic factor was signiifcantly increased in the dentate gyrus of the Oenanthe javanica extract-treated group compared with the control group. However, we did not ifnd that vascular endothelial growth factor expression was increased in theOenanthe javanica extract-treated group compared with the control group. These results indicate thatOenanthe javanica extract improves cell proliferation and neuroblast differentiation by increasing brain-de-rived neurotrophic factor immunoreactivity in the rat dentate gyrus.

Anti-melanoma action of small molecular peptides derived from Brucea javanica(L.)Merr.globulin in vitro

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.

Brucea javanica oil inhibits proliferation of hepatocellular carcinoma cells and induces apoptosis via the PI3K/AKT pathway

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.

Formulation and characterization of brucea javanica oil microemulsion

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.

Effect of preoperative Brucea javanica oil emulsion + conventional chemotherapeutic drugs intraperitoneal chemotherapy on the expression of oncogene in advanced gastric cancer after surgical resection

Objective: To study the effect of preoperative Brucea javanica oil emulsion + conventional chemotherapeutic drugs intraperitoneal chemotherapy on the expression of oncogene in advanced gastric cancer after surgical resection. Methods: The patients who were diagnosed with advanced gastric cancer in our hospital during the period of March 2015 to October 2017 were randomly divided into the combined group received preoperative Brucea javanica oil emulsion + conventional chemotherapeutic drugs intraperitoneal chemotherapy, control group received conventional chemotherapeutic drugs intraperitoneal chemotherapy. The tumor markers in serum were measured before and after chemotherapy, and the expression of oncogenes in the lesion was measured after operation. Results: After chemotherapy, the levels of CEA, CA199, G17 and TK1 in the serum of the two groups were significantly decreased and the decreasing trend of CEA, CA199, G17 and TK1 in the serum of the combined group was more significant than that of the control group. The mRNA expression of CyclinD1, FRA-1, Bmi-1, c-Met, HER-2, CAT-D, MMP2, MMP7 in gastric cancer of combined group were significantly lower than the control group, and the mRNA expression of PTEN, p16, KISS-1, Caspase-3, TSPYL-5, TIMP1, RECK were significantly higher than that of the control group. Conclusion: Preoperative Brucea javanica oil emulsion + conventional chemotherapeutic drugs intraperitoneal chemotherapy can more significantly regulate the expression of oncogene in gastric cancer than conventional chemotherapy drugs.

Study of Antiparasitic and Cytotoxicity of the Aqueous, the 80% Methanol Extract and Its Fractions, and the Acute Toxicity of the Aqueous Extract of Brucea sumatrana (Simaroubaceae) Leaves Collected in Mai-Ndombe, Democratic Republic of Congo

Results from the in vitro evaluation of the antiparasitaire activity of the aqueous extract, the 80% methanol extract and its fractions from the leaves of Brucea sumatrana against Trypanosoma brucei brucei, T. cruzi, Leishmania infantum, the multidrug-resistant K1 and chloroquine-sensitive NF54 strains of Plasmodium falciparum indicated that all samples from the leaves extract presented interesting antiparasitaire activity at different extents. The 80% methanol extract, its chloroform acid, petroleum ether and 80% methanol soluble fractions and the aqueous extract exhibited strong activity against Trypanosoma b. brucei, T. cruzi, L. infantum and the multidrug-resistant K1 strain of P. falciparum with IC50 values from <0.25 to 4.35 μg/ml as well as against chloroquine-sensitive NF54 strain of P. falciparum with IC50 values ranging from <0.02 to 2.0.4 μg/ml. Most samples were cytotoxic against MRC-5 cell lines (0.2 50) < 34.24 μg/ml) and showed good selective effect against all tested parasites. In acute toxicity, the aqueous extract was found to be non-toxic and its LD50 was estimated to be greater than 5 g/kg. In addition, it did not significantly modify the concentration levels of some evaluated biochemical and hematological parameters in treated rats. These results constitute a scientific validation supporting and justifying the traditional use of the leaves of B. sumatrana for the treatment of malaria, sleeping sickness and at some extent Chagas disease.

Effect of brucea javanica oil injection combined with neoadjuvant chemotherapy on malignant molecule expression and antitumor immune response in patients with gastric cancer

Objective:To study the effect of brucea javanica oil injection combined with neoadjuvant chemotherapy on malignant molecule expression and antitumor immune response in patients with gastric cancer.Methods: A total of 78 patients with gastric cancer undergoing preoperative neoadjuvant chemotherapy in our hospital between May 2013 and July 2016 were selected and randomly divided into two groups, intervention group received brucea javanica oil injection combined with neoadjuvant chemotherapy, and the control group accepted neoadjuvant chemotherapy. Serum tumor marker levels and peripheral blood regulatory molecule expression were determined before and after treatment, and the malignant molecule expression levels in gastric cancer lesions were determined after the operation.Results:2 cycles and 4 cycles after treatment, serum CEA, DKK1, exosc2 and ANXA2 levels of both groups of patients were significantly lower than those before treatment, PD-1, TIM-3 and Foxp3 mRNA expression in peripheral blood mononuclear cells of control group were significantly higher than those before treatment, PD-1, TIM-3 and Foxp3 mRNA expression in peripheral blood mononuclear cells of intervention group were significantly lower than those before treatment, serum CEA, DKK1, exosc2 and ANXA2 levels as well as PD-1, TIM-3 and Foxp3 mRNA expression in peripheral blood mononuclear cells of intervention group were significantly lower than those of control group, and the GKN1 and GKN2 mRNA expression in gastric cancer lesions were significantly higher than those of control group while GOLPH3 and PTP1B mRNA expression were significantly lower than those of control group.Conclusion:Brucea javanica oil injection combined with neoadjuvant chemotherapy can more effectively kill the gastric cancer cells and improve the antitumor immune response.

Exploring the Action Mechanism of Yadanzi(Brucea javanica)in the Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology

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.

鸦胆子石油醚提取物成分分析及降糖活性初探

目的:对鸦胆子石油醚提取物的主要成分进行分析,并对其降糖活性进行探讨。方法:采用石油醚萃取的方式提取鸦胆子,应用气相色谱-质谱联用技术(GC-MS)鉴定其成分,应用归一化法测定各成分的质量分数(相对含量)。色谱条件:色谱柱Agilent HP-5MS(30 m×250μm×0.25μm),流速1 mL/min,分流比15∶1,进样口温度300℃。程序升温条件:60℃保持5 min,以4℃/min升温至180℃,保持5 min,以2℃/min升温至280℃,保持10 min。质谱条件:离子源电子轰击(EI)源,离子源温度230℃,四级杆温度150℃,溶剂延迟3 min,电子能量70 eV,质荷比(m/z)范围50~900。数据库:NIST 08。降糖活性通过测试pNPG水解产物NPG的吸光计算而得。结果:从鸦胆子石油醚提取物成分中鉴定出脂肪酸、芳香酸、脂肪酸酯、醛、酮、萜、类固醇、烃类等53种成分,其中脂肪酸11种,脂肪酸酯20种,醛7种,烃9种,芳香酸1种,酮1种,萜1种,类固醇2种,生育酚1种。药理学研究表明,鸦胆子石油醚提取物具有α-葡萄糖苷酶抑制活性。结论:GC-MS能够高效准确快速鉴定鸦胆子石油醚提取物的化学成分,鸦胆子这一类成分的降血糖作用为进一步研究其作用机制奠定了基础。

鸦胆子结合吡柔比星对膀胱癌细胞作用的影响

目的探究鸦胆子结合吡柔比星对膀胱癌细胞的作用。方法选取2023年4—5月期间黑龙江省医院泌尿科1株人BIU-87膀胱癌细胞株为研究对象,细胞培养后,将其接种于96孔板中,以随机数表法分为5组,每组细胞均进行3个平行样本,每个样本细胞均设置5个复孔(每组共计15个样本量),将5组细胞以不同浓度鸦胆子油乳(0、5、10、20、30 mL/L)与吡柔比星(5μmol/L)联合作用,分析不同浓度鸦胆子油乳对膀胱癌细胞增殖抑制作用、细胞凋亡及细胞周期影响,并检测联合用药对核因子κB(Nuclear FactorκB,NF-κB)影响、对细胞中三磷酸腺苷(AdenosineTriphosphate,ATP)结合转运蛋白G家族成员2(ATP-bindingCassette TransporerG2,ABCG2)表达情况影响。结果鸦胆子油乳浓度升高,BIU-87细胞增殖抑制率、坏死率、凋亡率逐渐升高,差异有统计学意义(P均<0.05);鸦胆子油乳浓度为5 mL/L时细胞增殖抑制率、细胞坏死率显著提升,浓度≥10 mL后,细胞凋亡率显著提升,差异有统计学意义(P均<0.05);随鸦胆子油乳浓度升高,BIU-87细胞中S期细胞占比降低,C0/C1期细胞占比升高,差异有统计学意义(P均<0.05);随鸦胆子油乳浓度升高,细胞质中NF-κB表达量逐渐下降,细胞核中NF-κB表达量逐渐升高,细胞膜表面ABCG2表达量下降,差异有统计学意义(P均<0.05)。结论鸦胆子油乳结合吡柔比星,可抑制BIU-87膀胱细胞株增殖,低浓度可促进细胞坏死,高浓度可促进细胞凋亡,并促进NF-κB从细胞质转入细胞核中,抑制ABCG2表达,其效果均存在剂量依赖性。

鸦胆子苦醇通过TLR9-MyD88信号通路调控Hela细胞凋亡的机制研究

目的探究鸦胆子苦醇(Brusatol,BRU)通过TLR9-MyD88信号通路调控Hela细胞凋亡的分子机制。方法针对本实验室保存的Hela细胞,使用不同浓度(0、5.0、10.0、20.0、40.0、80.0 nmol·L^(-1))的鸦胆子苦醇处理细胞。并将Hela细胞分为Control组(正常培养的Hela细胞)、BRU-L组(使用10.0 nmol·L^(-1)的鸦胆子苦醇处理细胞)BRU-H组(使用20.0 nmol·L^(-1)的鸦胆子苦醇处理细胞)、BRU+pcDNA-NC组(转染pcDNANC+20.0 nmol·L^(-1)的鸦胆子苦醇)、BRU-H+pcDNA-TLR9组(转染pcDNA-TLR9+20.0 nmol·L^(-1)的鸦胆子苦醇)。使用细胞计数试剂盒(CCK-8)法和EdU法检测各组细胞增殖情况;TUNNEL染色法,经流式细胞仪检测细胞凋亡;蛋白免疫印迹(Western blot)检测各组细胞TLR9、MyD88、Bax、Bcl-2、Cleaved Caspase-3和Cleaved Caspase-9蛋白表达水平;流式细胞术检测细胞凋亡和线粒体膜电位检测试剂盒(JC-1)情况、ELISA检测各组细胞三磷酸腺苷(ATP)和活性氧基团(ROS)含量。结果与0 nmol·L^(-1)组比较,10 nmol·L^(-1)组细胞活存活率、IC50值开始显著降低(P<0.05)。不同浓度的BRU刺激细胞后,细胞增殖能力显著降低,且呈剂量依赖(P<0.05)。。与Control组比较,BRU-L、BRU-H组、BRU-H+pcDNA-NC组细胞5-乙炔基-2′-脱氧尿嘧啶核苷(EDU)阳性细胞率、缺口末端标记法(TUNEL)阳性细胞率、细胞凋亡率、细胞Bcl-2蛋白均显著降低,TLR9和MyD88蛋白、Bax、Bax/Bcl-2、Cleaved Caspase-3、Cleaved Caspase-9蛋白水平均明显增加(P<0.05);Control组、BRU-L、BRU-H组/BRU-H+pcDNA-NC呈持续递减/递减趋势(P<0.05);与BRU-H+pcDNA-NC组比较,BRU-H+pcDNA-TLR9组EDU阳性细胞率、TUNEL阳性细胞率、细胞凋亡率、细胞Bcl-2蛋白均显著升高,TLR9和MyD88蛋白、Bax、Bax/Bcl-2、Cleaved Caspase-3、Cleaved Caspase-9蛋白水平均明显降低(P<0.05)。与Control组比较,BRU-L、BRU-H组、BRU-H+pcDNA-NC组细胞JC-1水平和ATP含量显著降低,而ROC含量、mitotracker染色阳性细胞水平显著增加(P<0.05);与BRU-L组比较,BRU-H组、BRU-H+pcDNANC组JC-1水平和ATP含量进一步降低,而ROC含量、mitotracker染色阳性细胞水平进一步增加(P<0.05);与BRU-H+pcDNA-NC组比较,BRU-H+pcDNA-TLR9组细胞JC-1水平和ATP含量增加,而ROC含量、mitotracker染色阳性细胞水平降低(P<0.05)。结论鸦胆子苦醇可通过调控TLR9-MyD88信号通路制Hela细胞增殖。

鸦胆子油乳对肺癌A549细胞顺铂化疗的增敏作用及其机制

目的观察鸦胆子油乳对肺癌A549细胞顺铂化疗的增敏作用并分析其机制。方法体外培养人肺癌细胞A549,MTT法检测鸦胆子油乳、顺铂对细胞生长的抑制率,计算鸦胆子油乳、顺铂对细胞的半数抑制浓度(IC_(50)),观察不同浓度(2.44、9.77、78.12μg/mL)鸦胆子油乳对顺铂IC_(50)的影响。将A549细胞分为对照组、鸦胆子油乳组、顺铂组及鸦胆子油乳+顺铂组,对照组不做处理正常培养细胞,鸦胆子油乳组、顺铂组及鸦胆子油乳+顺铂组分别给予鸦胆子油乳单药、顺铂单药、鸦胆子油乳及顺铂联合处理。采用荧光显微镜观察细胞形态及生长情况,流式细胞术检测细胞周期及细胞凋亡率,二氯荧光素二乙酸酯荧光探针染色检测细胞内ROS水平。结果顺铂IC_(50)随着鸦胆子油乳处理浓度的增高而下降(P均<0.05)。对照组细胞生长较好,细胞数量较多且形状为正常生长状态;顺铂组及鸦胆子油乳组细胞数量较对照组均减少,可见少量碎片;鸦胆子油乳+顺铂组细胞生长受抑制较明显,细胞数量最少,细胞形状不规则且细胞碎片增多。G_(0)/G_(1)期细胞比例鸦胆子油乳+顺铂组>顺铂组、鸦胆子油乳组>对照组,细胞凋亡率鸦胆子油乳+顺铂组>鸦胆子油乳组、顺铂组>对照组,细胞内ROS水平鸦胆子油乳+顺铂组>鸦胆子油乳组、顺铂组>对照组(P均<0.05)。结论鸦胆子油乳能够增加肺癌A549细胞对顺铂化疗的敏感性,其机制可能与阻滞肿瘤细胞于G_(0)/G_(1)期、增加活性氧产生从而促进细胞凋亡有关。

鸦胆子油乳注射液使用情况及合理性分析

目的 通过泰州市人民医院鸦胆子油乳注射剂使用情况的分析,加强该药在临床的合理使用,确保用药安全。方法 选取我院2022年度使用鸦胆子油乳注射液进行治疗的798例患者,分析该药治疗的肿瘤类型、不同科室使用情况、不良反应发生情况。结果入选的798例患者中,男性患者527例,女性271例;年龄29~92岁,平均年龄66.36±10.92岁。肿瘤类型最多的为食管恶性肿瘤,共计131例(16.42%),其次为肝脏恶性肿瘤与肺恶性肿瘤,分别为118例(14.79%)和116例(14.54%)。鸦胆子油乳注射液用量最大的科室胃肿瘤科,共有370例(46.37%),其次为消化内科病房与肝病科病房,分别有144例(18.05%)和102例(12.78%)。全部患者中,共出现6例不良反应,均为轻微不良反应。结论 鸦胆子油乳注射液在临床使用过程中,应严格按照适应症用药,同时应关注患者不良反应发生情况,确保临床用药安全。

鸦胆子中苦木素类成分及其抗炎机制的研究进展

鸦胆子是我国传统中药之一,其主要活性化学成分是苦木素类化合物,具有抗肿瘤、抗炎、抗病毒等药理作用。本文通过整理、归纳和分析现有的苦木素类化合物研究成果,探讨具有抗炎活性的化合物结构的异同及其作用机制。苦木素类化合物中的A环、C环和D环上的α,β-不饱和酮、糖基、烯键的取代能影响其抗炎活性。这些化合物主要通过调控细胞内信号传导通路NF-κB发挥抗炎作用,此外,它们还能抑制多种促炎因子的表达,包括TNF-α、IL-6、IL-β等,从而有效地抑制炎症反应。苦木素类化合物的抗炎活性可能与其抗补体活性相关,特别是与补体蛋白C3a和C5a有关。

鸦胆子油乳注射液对结肠炎相关性结直肠癌小鼠的作用及机制研究

目的:建立结肠炎相关性结直肠癌(CAC)小鼠模型,研究鸦胆子油乳注射液(BJOEI)的抗癌作用及机制。方法:将60只SPF级C57BL/6雄性小鼠随机分为正常组、模型组、阿司匹林组和BJOEI低、中、高剂量组,每组10只。除空白组外,各组小鼠均采用氧化偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)诱导CAC小鼠模型,从第3周开始,各组予以相应药物治疗,阿司匹林组25 mg/kg灌胃,BJOEI低、中、高剂量组分别以1.5 mL/kg、3.0 mL/kg、4.5 mL/kg剂量腹腔注射BJOEI,空白组和模型组腹腔注射等体积生理盐水,1次/d,连续给药10周后取材并记录结直肠肿瘤个数,计算脾脏指数;HE染色观察小鼠的结肠组织病理变化,并进行病理学评分;ELISA法检测小鼠血清白细胞介素(IL)-6水平;免疫组化检测结肠组织Ki67、肿瘤坏死因子(TNF)-α和血管内皮生长因子(VEGF)的表达;Western blot检测结肠组织磷酸化核因子-κB(p-NF-κB)/NF-κB蛋白相对表达量。结果:与模型组相比,BJOEI低、中、高剂量组肠道肿瘤个数和脾脏指数均减少,有统计学意义(P<0.05),肠组织病理学评分和Ki67、TNF-α、VEGF、p-NF-κB/NF-κB表达水平均降低,有统计学意义(P<0.05),BJOEI中、高剂量组血清IL-6水平降低,有统计学意义(P<0.05)。结论:BJOEI可能通过抑制NF-κB通路来减轻肠黏膜炎症反应发挥抗CAC作用。

鸦胆子油乳联合放疗对中老年食管癌患者血清肿瘤标志物及生活质量的影响

目的探讨鸦胆子油乳联合放疗在中老年食管癌患者中的疗效。方法选取2019年1月至2022年12月南通市通州区人民医院收治的96例中老年食管癌患者为研究对象,按照随机数字表法分为对照组与观察组,各48例。对照组实施放疗,观察组在对照组基础上加用鸦胆子油乳治疗。比较两组患者血清肿瘤标志物、临床疗效、生活质量及不良反应。结果观察组患者治疗后血清肿瘤标志物中的糖类抗原199(CA199)、糖类抗原125(CA125)及癌胚抗原(CEA)水平均低于对照组,差异有统计学意义(P<0.05);观察组患者疾病控制率高于对照组,差异有统计学意义(P<0.05);观察组患者治疗后生活质量综合评定问卷(GQOLI-74)中各维度评分均高于对照组,差异有统计学意义(P<0.05);观察组患者不良反应总发生率低于对照组,差异有统计学意义(P<0.05)。结论针对中老年食管癌患者实施鸦胆子油乳联合放疗,能够降低患者血清肿瘤标志物水平,获得较好的疾病控制效果,还可减少不良反应的发生,提升生活质量。