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Background Although brucea javanica oil liposomes (BJOLs) have been used clinically to treat ovarian cancer, its clinical efficacy is often limited by systemic side effects due to non-specific distribution. Luteinizing hormone releasing hormone receptor (LHRHR) is overexpressed in most ovarian cancers but negligibly expressed in most of the other visceral organs. In this study, we aimed to develop a novel LHRHa targeted and BJO-loaded liposomes (LHRHa-BJOLs), and investigate its characteristics, targeting ability and anti-ovarian cancer efficiency both in vitro and in vivo. Methods The LHRHa-BJOLs were prepared by film-dispersion and biotin-streptavidin linkage methods, and characterized in terms of its morphology, particle size, zeta potential, ligand conjugation, encapsulation efficiency and stability. The targeting nature and antitumor effects of the liposomes were evaluated in vitro using cultured human ovarian cancer A2780/DDP cells, and in vivo using ovarian cancer-bearing nude mice. Results The LHRHa-BJOLs were successfully synthesized, with a uniformly spherical shape, appropriate particle size and zeta potential, as well as a high encapsulation efficiency. Compared to non-targeted liposomes and BJO emulsion, the LHRHa-BJOLs could significantly increase specific intracellular uptaking rate, enhance cell inhibitory effect and induce cell apoptosis in A2780/DDP cells in vitro. Meanwhile, LHRHa-BJOLs also had a significantly stronger activity of targeting tumor tissue, inhibiting tumor growth, inducing tumor apoptosis and prolonging survival time in ovarian cancer-bearing mice in vivo. Conclusions Our experiment suggests that LHRHa-BJOLs may be a useful targeted drug for the treatment of ovarian cancer.

To analyze the protein composition of Brucea javanica seeds and evaluate the cytotoxicity of its gulbulin hydrolysates. Four protein fractions of albumin, gulbulin, prolamin and glutelin were sequentially extracted and then quantified by Kjeldahl method. Different kinds of proteases were applied to hydrolyze B.javanica gulbulin, and MTT assay was used to evaluate the cytotoxicity of low molecular weight hydrolysates (≤3 kDa) on human breast cancer MCF-7 cell. The results showed that： the total protein content of B.javanica seeds was 17.47%, albumin, gulbulin, coxin, glutelin and residue protein accounted for 15.01%, 8.11%, 2.47%, 44.92% and 23.62% of the total protein content, respectively. The hydrolysates (≤3 kDa) of B.javanica globulin produced by pepsin showed significant growth inhibitory activity on MCF-7 cells, and the IC₅₀ value was（6.52±0.01） mg•L⁻¹ after 72 h of incubation. Protein was abundant in B.javanica seeds, and its peptides demonstrated specific cytotoxicity on MCF-7 cell line in vitro, suggesting antitumor active ingredient can be further generated from B.javanica seeds.

Sponge-type nanocarriers (spongosomes) are produced upon dispersion of a liquid crystalline sponge phase formed by self-assembly of an amphiphilic lipid in excess aqueous phase. The inner organization of the spongosomes is built-up by randomly ordered bicontinuous lipid membranes and their surfaces are stabilized by alginate chains providing stealth properties and colloidal stability. The present study elaborates spongosomes for improved encapsulation of Brucea javanica oil (BJO), a traditional Chinese medicine that may strongly inhibit proliferation and metastasis of various cancers. The inner structural organization and the morphology characteristics of BJO-loaded nanocarriers at varying quantities of BJO were determined by cryogenic transmission electron microscopy (Cryo-TEM), small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Additionally, the drug loading and drug release profiles for BJO-loaded spongosome systems also were determined. We found that the sponge-type liquid crystalline lipid membrane organization provides encapsulation efficiency rate of BJO as high as 90%. In vitro cytotoxicity and apoptosis study of BJO spongosome nanoparticles with A549 cells demonstrated enhanced anti-tumor efficiency. These results suggest potential clinical applications of the obtained safe spongosome formulations.

A green fluorescent protein (GFP)-tagged pepper mottle virus (PepMoV) based leaf-disc method and systemic host method were developed to identify antiviral agents. Preliminary experiments using a PepMoV-GFP based leaf-disc method led to the isolation of five quassinoids, including brusatol (1), bruceantin (2), brucein A (3), bruceantinol (4), and brucein B (5), from the CH3OH extract of Brucea javanica. All isolated compounds exhibited inactivation effects in systemic host plants, and compounds 3 and 4 were potent, with a minimum inhibitory concentration of 10μM. Furthermore, compound 3 was found to have a protective effect at the tested concentration of 40μM.

Many anticancer drugs are obtained from natural sources. Nature produces a variety of toxic compounds, which are often used as anticancer drugs. Up to now, there are at least 120 species of poisonous botanicals, animals and minerals, of which more than half have been found to possess significant anticancer properties. In spite of their clinical toxicity, they exhibit pharmacological effects and have been used as important traditional Chinese medicines for the different stages of cancer. The article reviews many structures such as alkaloids of Camptotheca acuminata, Catharanthus roseus and Cephalotaxus fortunei, lignans of Dysosma versipellis and Podophyllum emodi, ketones of Garcinia hanburyi, terpenoids of Mylabris and Ginkgo biloba, diterpenoids of Tripterygium wilfordii, Euphorbia fischeriana, Euphorbia lathyris, Euphorbia kansui, Daphne genkwa, Pseudolarix kaempferi and Brucea javanica, triterpenoids of Melia toosendan, steroids of Periploca sepium, Paris polyphylla and Venenum Bufonis, and arsenic compounds including Arsenicum and Realgar. By comparing their related phytochemistry, toxic effects and the recent advances in understanding the mechanisms of action, this review puts forward some ideals and examples about how to increase antitumour activity and/or reduce the side effects experienced with Chinese medicine.

To evaluate the therapeutic efficacy and side effects of oral Fructus bruceae oil combined with radiotherapy in the treatment of esophageal cancer.A total of 80 patients with esophageal cancer were equally and randomly divided into two groups. The patients in Group A were treated with radiotherapy (60-65 Gy, 6-7 weeks) and oral Fructus bruceae oil (20 mL, 3 times per day for 12 weeks), while the patients in Group B were treated with radiotherapy alone. The short-term effect was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) and quality of life (QOL) was evaluated by the Karnofsky scoring (KFS). The outcome measures included complete remission (CR) rate, partial remission (PR) rate, effective rate as CR+PR, patients' QOL and adverse effects.After 12-week treatment, the CR and CR+PR were significantly higher in Group A than those in Group B (P0.05). There was an improvement in esophageal obstruction of 87.5% and 60.0%, respectively, and in KFS of 84.6% and 43.9%, respectively, in Groups A and B.Oral medication with oral Fructus bruceae oil could effectively improve the efficacy of radiotherapy in esophageal cancer, including a reduction in esophageal obstruction, and also reduce the side effects of radiotherapy; thus it would be very promising for clinical application.

A new pregnane glycoside, named (20R)-O-(3)-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl-pregn-5-en-3β,20-diol (1), and seven known compounds, brusatol (2), bruceine B (3), bruceine D (4), yadanziolide A (5), bruceine E (6), yadanzioside G (7), and yadanzioside B (8), were isolated from the cultivated dry seeds of Brucea javanica. The structure of 1 was elucidated on the basis of 1D- and 2D-NMR spectroscopic analyses. Their inhibitory effects on tumor cells were also tested. Compound 1 was slightly active against HL-60, SMMC-7721, A-549, and MCF-7 tumor cells. Compounds 2 and 3 demonstrated significant inhibitory activities against all tested cells. These results indicate that cultivated B. javanica could replace the wild plant as an antitumor plant resource.

Our previous studies showed that the alcohol extract of the fruit of Brucea javanica (Fructus Bruceae) possessed significant cytotoxicity in pancreatic adenocarcinoma cell lines. A bioassay-guided fractionation and purification resulted in the isolation and characterization of seven quassinoids including brusatol, bruceine D, bruceine H, yadanzioside A, yadanzioside G, javanicoside C and bruceantinoside A. Among them, brusatol exhibited the most potent in vitro antipancreatic cancer action, with IC50 values of 0.36 µm and 0.10 µm on PANC-1 and SW1990 cell lines, respectively. This is the first report on the antipancreatic adenocarcinoma activity of brusatol. Copyright © 2011 John Wiley & Sons, Ltd.

Objective The aim of this study was to evaluate the effects and safety of brucea javanica oil, mitomycin and BCG for preventing postoperative relapse of superficial bladder cancer through perfusion.

Three new pregnane glycosides, 3-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl-(20R)-pregn-5-ene-3β,20-diol (1), 3-O-α-L-arabinopyranosyl-(20R)-pregn-5-ene-3β,20-diol-20-O-β-D-glucopyranoside (2), 3-O-α-L-arabinopyranosyl-(20R)-pregn-5-ene-3β,20-diol-20-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside (3) were isolated along with four known compounds, 4-7, from the leaves and stems of Brucea javanica. Their structures were determined by detailed analyses of 1D- and 2D-NMR spectroscopic data. All of the compounds isolated from Brucea javanica were tested for the antifeedant activities against the larva of Pieris rapae. Compounds 1, 3, and 5 showed significant antifeedant activities after 72 h incubation.

Objective: This study aimed to determine a target of action of bruceine A on the basis of its morphological and histological effects on the larvae of Aedes aegypti Linnaeus.Methods: Bruceine A was isolated from Brucea javanica (L.) Merr. seeds in accordance with the Mangungsong method. Larvae of A. Aegypti (L.) in instar III to the beginning of instar IV were treated with various concentrations of bruceine A. The negative control group did not receive any treatment, whereas the positive control group received 1 ppm temefos. Dead larvae were collected after 24 h of treatment for the examination of morphological and histological changes.Results: The negative control group did not exhibit any morphological and histological changes. Larvae treated with bruceine A, however, had visible damaged heads, cuticles, digestive and respiration tracts, respiratory siphons, and setae, and they were smaller than normal larvae. Larvae treated with temefos exhibited gastrointestinal damage, narrowed breathing tubes, cuticle damage, and detached/damaged seta feathers. The necrosis of gastrointestinal epithelial cells was the major histological change exhibited by larvae treated with various concentrations of bruceine A or 1 ppm temefos.Conclusion: The targets of action of bruceine A in A. aegypti (L.) larvae are the head/caput, cuticle, setae, siphon, and gastrointestinal and respiratory tracts.

Brucea javanica oil-loaded liposomes (BJOL) were prepared through thin film hydration method and characterized by transmission electron microscope, dynamic light scattering, and differential scanning calorimetry. Acute toxicity of B. javanica oil (BJO) in liposomes was assessed by determining the number of deaths of Kunming mice over intravenous treatment for 2 weeks. The pharmacokinetic behavior of the main active component (oleic acid) was studied in SD rats. The pharmacodynamics of BJOL was investigated using MMC-7721 cell lines and mice with Lewis lung cancer. The commercial emulsion of BJO (BJOE) was used as a reference. The data showed that BJOL had an average diameter of 108.2 nm with a zeta potential of -57.0 mV, drug loading of 3.60%, and entrapment efficiency of 92.40%. The area under curve of BJO in liposomes and emulsions were 2.31 and 1.15 mg min/ml, respectively. Compared with BJOE, mean residence time and elimination half-time (t(1/2)) increased 2.8- and 4.0-fold, respectively, and the clearance (CL) decreased 0.5-fold. In the acute toxicity test, the median lethal dose (LD(50)) of BJOE was 7.35 g/kg. In contrast, all mice treated with liposomes survived even at the highest dosage (12.70 g/kg). The IC(50) value of BJOL group was one third of that of BJOE group (p < 0.01), and a less weight loss was observed in the BJOL-treated animals (p < 0.05). In conclusion, the present study suggests that BJOL significantly decreased toxicity of BJO and enhance the antitumor activity. Therefore, liposomes may be a potential effective delivery vehicle for this lipophilic antitumor drug.

Two new quassinoids, javanicolide E (1) and javanicolide F (2), along with fifteen known C-20 quassinoids were isolated from the seeds of Brucea javanica (L.) Merr. The antitobacco mosaic virus (TMV) activity of these quassinoids was screened by the conventional half-leaf and leaf-disk method along with Western blot analysis. All of the seventeen quassinoids showed potent anti-TMV activity. Among them, eight compounds, brusatol (3), bruceine B (4), bruceoside B (5), yadanzioside I (6), yadanzioside L (7), bruceine D (8), yadanziolide A (9), and aglycone of yadanziolide D (17), showed strong antiviral activities, with IC(50) values in the range of 3.42-5.66 microM, and were much more effective than the positive control, ningnanmycin (IC(50) = 117.3 microM). The antiviral structure-activity relationships of quassinoids against TMV were also discussed.

Current chemotherapeutic options for African trypanosomiasis in humans and livestock are very limited. In the present study, a total of 71 medicinal plant specimens from 60 plant species collected in Myanmar were screened for antitrypanosomal activity against trypomastigotes of Trypanosoma evansi and cytotoxicity against MRC-5 cells in vitro. The methanol extract of dried rootbark of Vitis repens showed the highest antitrypanosomal activity with IC(50) value of 8.6 +/- 1.5 microg/ml and the highest selectivity index of 24.4. The extracts of Brucea javanica, Vitex arborea, Eucalyptus globulus and Jatropha podagrica had also remarkable activity with IC(50) values and selectivity indices in the range of 27.2-52.6 microg/ml and 11.4-15.1 respectively.

Ethnopharmacological relevance The seeds of Brucea javanica (L.) Merr (Simaroubaceae) are recommended by traditional practitioners for the treatment of diabetes mellitus. Aim of the study To identify the compounds responsible for blood glucose lowering effect and evaluate the acute toxicity of the compounds. Materials and methods Extracts, fractions and subfractions were administered to normoglycemic mice and the blood glucose concentration was monitored for 8 h. Bioactive compounds isolated through column chromatography were administered to normoglycemic mice and streptozotocin (STZ) rats with monitoring of blood glucose concentration at 0–8 h. The acute toxicity was evaluated in mice. Results Bioactivity-guided fractionation led to the isolation of bruceines E ( 1 ) and D ( 2 ). Normoglycemic mice administered with 1 mg/kg of 1 and 2 exhibited significant blood glucose concentration reduction of 40.07 ± 11.45% and 48.82 ± 13.34%, respectively. STZ induced diabetic rats administered with 1 and 2 exhibited significant blood glucose concentration reduction of 73.57 ± 13.64% and 87.99 ± 2.91%, respectively. Conclusion The reduction of blood glucose concentration by both bruceines was comparable to glibenclamide and they might act as an insulin secretagogue. The presence of a hydroxyl moiety at C 2 in 1 reduced the toxic effect by 9-fold compared to 2 .

Three new constituents were obtained along with 10 known compounds from the seeds of Brucea javanica. The structures of these compounds were determined based on spectral and chemical evidence. These new compounds included a monoterpenoid glycoside and two sesquiterpenes. Bioactivity screening of these constituents showed that compounds 1, 3, 8, 9, and 13 with obvious activities in inhibiting multiplication of the Tobacco mosaic virus.

Bruceine A, a natural quassinoid compound extracted from the dried fruits of Brucea javanica (L.) Merr., was evaluated for its antibabesial activity in vitro and in vivo. Bruceine A inhibited the in vitro growth of Babesia gibsoni in canine erythrocytes at lower concentration compared with the standard antibabesial drug diminazene aceturate and killed the parasites within 24 hr at a concentration of 25 nM. Oral administration of bruceine A at a dosage of 6.4 mg/kg/day for 5 days resulted in no clinical findings in a dog with normal ranges of hematological and biochemical values in the blood. Three dogs were infected with B. gibsoni and two of them were treated with bruceine A at a dosage of 6.4 mg/kg/day for 6 days from day 5 post-infection. An untreated dog developed typical acute babesiosis symptoms including severe anemia, high fever, and complete loss of appetite and movement. However, the two bruceine A-treated dogs maintained their healthy conditions throughout the experimental period of 4 weeks although complete elimination of parasites from the peripheral blood was not achieved and decreases in the packed cell volume and the erythrocyte and platelet counts were observed. Since natural quassinoid compounds have been used as traditional medicines for the treatment of various ailments including cancer and malaria, the present results suggest that bruceine A or other related compounds are potential candidates for the treatment of canine babesiosis.

In an attempt to increase the productivity of the pharmaceutical compound canthin-6-one from cell suspension culture of Brucea javanica, a high cell density culture and improved culture conditions have been investigated with focus on culture conditions and stages of growth. The highest yield of canthin-6-one, 26.72 mg g -l dry cell, was produced intracellular in 50 g L -1 cell mass. The established cell suspensions were harvested at the age of 40 days and placed into MS medium containing 1.0 mg L-1 2,4-D, 1.0 mg L-1 NAA, 0.1 mg L-1 Kinetin and 10 mg L -1 tryptophan for 33-40 days, approximately when the cultures were at their late stationary phase of growth. Addition of 20 mg L -1 tryptophan did not show a significant difference in canthin-6-one production (p>0.05). Higher than 10 mg L -1 of tryptophan showed adverse effect on the concentration of canthin-6- one alkaloid (p=0.01). Qualitative analysis of chloroform-extracts of dried cells from suspension cultures revealed spots on TLC; and the identity of canthin-6-one was established by comparison of its Rf value (Rf=0.37), its colour reaction with Dragendorff reagent and ammonium sulphate and its behaviour in UV with an authentic sample. Quantification of canthin-6-one alkaloid using TLC- densitometry scanner in response to different concentration of tryptophan as a precursor showed a concentration-dependent response. The production of canthin-6-one at 26.72 mg g -1 dried cell weight in this study, establishes a methodology of an improved procedure compared to those previously reported and offers an opportunity for production of canthin-6-one alkaloid at an industrial level.

Research on the effect of maturated stages and soaking treatment of water and Giberrelic Acid hormone on Brucea javanica germination was carried out at Macropropagation Laboratory, Research Centre of Biology, LIPI, Cibinong-Bogor. The research study arranged by Factorial in Completely Randomized Design with 2 factors and 3 replications, each replication with 20 seeds sample. The first factor was maturated stage of fruits with 3 levels factor i.e. green, brown and black peels, and the second factor was soaking treatment with 6 levels factor i.e. 0 (control), 1, 3 days in water, 500, 1000, 1500 mg/L in GA3 solution. The results showed that the maturated stage had significant on seeds germination of B. javanica. The black peel of maturated stage of fruit was the best factor on chosen on B. javanica seedling, in comparing with brown and green peels. Soaking treatment in GA3 solution was effective on trigger of seeds germination of B. javanica. The combination treatment of black peel maturated stage with 1500 mg/L GA3 solution were the best result for all parameter observation i.e. on the first germination (4 days), rich germination 50% (10 days), germination percentage (93.33%) and germination value (7.074). But in the control were first germination (10 days), rich germination only 20% (no rich 50%), germination percentage (93.33%) and germination value (0.148).© 2008 Jurusan Biologi FMIPA UNS SurakartaKey words: maturity stages, soaking, water, GA3, seeds germination, Brucea javanica (L.) Merr

The purpose of this study was to prepare and evaluate the intravenous emulsion (BCOE) containing Brucea javanica oil (BJO) and Coix seed oil (CSO), which is used in anti-tumor treatment. The formulation and preparation of BCOE were systematically investigated. High-pressure homogenization, particle size distribution, zeta-potential and HPLC were carried out. The pharmacokinetics of the main component, oleic acid, and anti-tumor activity studies about the tumor growth inhibitory ratios (TGIR) and the mortality experiments were also employed to evaluate BCOE in vivo compared with BJO emulsion (BJOE) and CSO emulsion (CSOE) using S180 sarcoma-bearing mice. The final BCOE formulation was 10% (w/v) oils with BJO and CSO 3 : 1, 0.6% (w/v) Lipid E 80, 0.3% (w/v) Pluronic F-68 (F-68), 0.1% (w/v) sodium oleate and 2.5% (w/v) glycerin in water. The preparation conditions involved 70 degrees C for preparing the crude emulsion, 6 cycles for high-pressure homogenization at 500 bar, pH value was adjusted to 8.5 after high-pressure homogenization and 115 degrees C for 30 min in a rotating water bath for sterilization. The pharmacokinetics parameters showed the combination of BJO and CSO may not influence the elimination of BCOE and have no significant difference between BCOE and BJOE or CSOE. The data of TGIR and mortality indicated that BCOE could increase the anti-tumor activity of CSOE and reduced the toxicity of BJOE. The mortality study (BCOE 0, BJOE 63.3%, CSOE 13.3%) showed that BCOE greatly reduced the toxicity of BJOE and CSOE. Therefore, the development and application of BCOE will make an important contribution to anti-tumor therapy.

Brucea javanica fruit is thought to have anticancer properties in Chinese medicine and its extract has been shown to possess antiproliferative and pro-apoptotic activities on human carcinoma cells. In the present study we demonstrated for the first time that Fructus Bruceae extract exhibited cytotoxic effects on the three pancreatic adenocarcinoma cell lines, PANC-1, SW1990 and CAPAN-1; the effects were comparable to those exhibited by camptothecin in our culture system. In addition, Fructus Bruceae extract induced fragmentation of genomic DNA, as evidenced by Hoechst staining and the cell death detection ELISAPLUS assay. Western blot analysis further showed down-regulation of pro-caspase 3 protein expression, indicating that the observed cytotoxic effects of the extract were associated with induction of apoptosis. These findings are not only significant in the development of traditional Chinese medicine as an alternative treatment for pancreatic cancer, but also in the elucidation of the potential mechanism(s) of Fructus Bruceae extract in cancer therapy. Copyright © 2008 John Wiley & Sons, Ltd.

Boiled extracts derived from 28 Indonesian medicinal plants were screened for their antibabesial activity against Babesia gibsoni in vitro. Of these extracts, the fruit of Brucea javanica was the most active in inhibiting parasite growth at a concentration of 10 microg/mL. Bioassay-guided fractionation of the fruit extract of Br. javanica led to the isolation of two new quassinoids, bruceantinol B and bruceine J, and the structures of these compounds were elucidated on the basis of their spectroscopic data and by chemical transformation to known compounds. In addition, the known quassinoids bruceines A-D, bruceantinol, and yadanziolide A were isolated. Antibabesial activities were also examined in vitro, and bruceine A and bruceantinol were shown to be more potent than diminazene aceturate, a drug (IC50 = 103 ng/mL) used clinically against B. gibsoni, with IC50 values of 4 and 12 ng/mL, respectively.

A new quassinoid, bruceene A (1) along with seventeen known quassinoids (2–18) was isolated from the fruits of Brucea javanica. The structure of 1 was elucidated by extensive spectroscopic methods, and was further confirmed by single-crystal X-ray diffraction analysis. Isolation of similar quassinoids 1–3 as those in genus Ailanthus from genus Brucea, indicated the close chemotaxonomic relationship between these two genera, which further supported the phylogenetic study by DNA analysis. Compounds 5, 7, 10 and 12 with a 3-hydroxy-3-en-2-one moiety showed potent inhibitory activities against the MCF-7 and MDA-MB-231 cells with IC50 values in the ranges 0.063–0.182 μM and 0.081–0.238 μM, respectively; while glycosidation at 3-OH significantly decreased the cytotoxicity. It was also found that the most potent compound 7 induced apoptosis in MCF-7 cells via the intrinsic mitochondrial apoptotic pathway.

Brucea javanicais a traditional herbal medicine in China, and its antitumor activities are of research interest.Brucea javanicaoil, extracted with ether and refined with 10% ethyl alcohol fromBrucea javanicaseed, was used to treat hepatoma H22-bearing mice in this study. The antitumor effect and probable mechanisms of the extractedBrucea javanicaoil were studied in H22-bearing mice by WBC count, GOT, GPT levels, and western blotting. The H22 tumor inhibition ratio of 0.5, 1, and 1.5 g/kg bwBrucea javanicaoil were 15.64%, 23.87%, and 38.27%.Brucea javanicaoil could inhibit the involution of thymus induced by H22 tumor-bearing, but it could not inhibit the augmentation of spleen and liver.Brucea javanicaoil could decrease the levels of WBC count and GOT and GPT in H22-bearing mice. The protein levels of GAPDH, Akt, TGF-β1, andα-SMA in tumor tissues decreased after being treated withBrucea javanicaoil. Disturbing energy metabolism and neoplastic hyperplasia controlled by Akt and immunoregulation activity were its probable antitumor mechanisms in hepatoma H22-bearing mice.

Multidrug delivery devices are designed to take advantage of the synergistic effects of anticancer agents in combination therapies. Here we report novel liquid crystalline self-assembled nanocarriers enhancing the activity of the phytochemical anticancer agent baicalin (BAI) in combination with Brucea javanica oil (BJO), which ensures safe formulations for clinical applications. Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) evidenced the multicompartment, sponge-type nano-organization of the blank and multidrug-loaded liquid crystalline carriers. Physico-chemical stability of the sponge nanoparticles was achieved through PEGylation of the lipid membranes, which make up the drug nanocarriers. The proposed green nanotechnology for nanocarrier preparation by supramolecular self-assembly provided a multidrug encapsulation efficiency as high as 75%. The apoptosis study with the human lung carcinoma cell line A549 demonstrated improved efficacy of the multidrug delivery nanocarriers in comparison to the single-drug reservoirs. The obtained results evidenced the synergistic anticancer apoptotic effects of the multidrug-loaded nanosponge carriers and suggested the opportunity for in vivo translation towards the treatment of lung, gastrointestinal, and ovarian cancers.

The in vitro antiplasmodial activity of 117 aqueous, methanol and dichloromethane extracts derived from different parts of 28 indigenous wild plant species was studied. These plants are commonly used in Cambodian traditional medicine. The plant extracts were tested for in vitro activity against a chloroquine resistant Plasmodium falciparum strain (W2). Nine extracts were moderately active with IC(50) values ranging between 5 and 10 microg/ml, 17 extracts were active with IC(50) values ranging between 1 and 5 microg/ml. These 26 extracts derived from eight plants belong to six families. The most active extracts were dichloromethane and came from Stephania rotunda and Brucea javanica with IC(50) values of 1 microg/ml and a selectivity indexor = 25. It is interesting to note that some aqueous extracts were as active as dichloromethane extracts especially aqueous extracts of Stephania rotunda, Brucea javanica, Phyllanthus urinaria and Eurycoma longifolia with IC(50) values ofor = 4 microg/ml. These results are in agreement with statements of healers on traditional uses of these plants for the treatment of malaria and/or fever. In this study, we report the antiplasmodial potential activity of eight plant species from Cambodia. Among them four are tested for the first time.

Aqueous rinds extract of Brucea javanica (L.) Merr has been used as the medium/reducing system for the formation of silver nanoparticles colloids. A solution of 0.01 N AgNO3 (1 ml) was added to the rind extracts (4 ml) at room temperature, and the formation of silver nanoparticles was observed using ultraviolet–visible spectrophotometer. The shape and size of the nanoparticles have been characterized using Transmission Electron Microscope (TEM) analysis. The experimental results show that the silver nanoparticles are formed easily in the extract at ambient temperature. The resulting nanoparticles were in the spherical form and the average size of the nanoparticles was about 38.00±14.00 nm.

Quassinoid glucosides, javanicosides I, J, K and L, were isolated from the seeds of Brucea amarissima (Lour.) Desv. ex B. A. Gomes (Simaroubaceae), along with two known quassinoids, i.e. bruceins D and E, and seven known quassinoid glucosides, yadanziosides B, C, E, I and K, bruceoside B and yadanzigan. Their structures were elucidated by analysis of the spectral data and chemical evidence.

Two new quassinoids, javanicolides C and D, and five new quassinoid glucosides, javanicosides B-F, were isolated from the seeds of Brucea javanica, along with eight known quassinoids, i.e., yadanziolides A, C, D, and S, bruceins D and E, brusatol, and the aglycone of yadanzioside D, and 19 known quassinoid glucosides, i.e., yadanziosides A-G, I, and K-P, bruceosides A-C and E, and bruceantinoside A. Their structures were elucidated by analysis of spectroscopic data and chemical evidence.

Two novel quassinoids, javanicolides A and B, and one novel quassinoid glucoside, javanicoside A were isolated from the seeds of Brucea javanica Merr. (Simaroubaceae), along with four known quassinoids, yadanziolides A and D, and bruceins D and E, and two known quassinoid glucosides, yadanziosides D and L. Their structures were elucidated by the analysis of spectral data and chemical evidence.

The objective of the study was to evaluate the oral acute toxicity of Brucea javanica Merril extract on both Male and Female DDY-Mice. Brucea javanica leaves have activity as a cytotoxic, anti-diarhhea, etc. Brucea javanica leaves extract was administered orally for first 24 hours at various dose levels (562.5mg/kg bw, 1125 mg/kg bw, 2250 mg/kg bw, and 4500 mg/kg bw) to determine the toxicity effects. The treatment groups were compared to the normal control. Vital organs (liver, heart, lymph, lungs, etc) and body weight were analyzed to study the toxicity. LD50 determined using Reed and Munich formula. Vital organs average weight showed no difference between control group and treatment groups from the lowest dose until the highest dose. In addition, the body weight data showed no difference between control group and treatment groups. LD50 for Brucea javanica extract using Reed and Munich formula was 1003.65 mg/kg bw. The result of the study showed that extract were categorized as “slightly toxic”.

A new quassinoid, yadanziolide S (1), was isolated from the seeds of the traditional Chinese medicinal herb, Brucea javanica, along with ten known compounds, flazin, bruceine D, yadanziolide B, bruceoside A, yadanziolide S, yadanzigan, glycerol 1,3-bisoleate, azelaic acid, (+/-)-8-hydroxyhexadecanoic acid, and vanillin. Compound 1 is the first quassinoid to have been isolated from B. javanica without a methyleneoxy bridge between C-8 and C-13, and its structure was determined using spectroscopic methods, and confirmed by single-crystal X-ray diffraction. All isolates were evaluated for their potential to induce human promyelocytic leukemia (HL-60) cell differentiation, and to inhibit cyclooxygenase-1 (COX-1), -2 (COX-2), and 7,12-dimethylbenz[a]anthracene (DMBA)-induced lesions in a mouse mammary organ culture model.

Brucea javanica (L) Merr is a local plant used traditionally for diabetic medication in Lombok Island. The B. javanica seed has been recognized to have an antidiabetic effect, while the impact of the leave extract was understudied. The purpose of this research was to determine the effect of B. javanica leaves infusion on the blood glucose level of alloxan-induced diabetic rats. B. javanica leaves extract were applied by soaking leaves into hot water (95°C) to obtain the extract concentration of 5% (w/v). This experiment provides four treatments to rats within 15 days with five replicates for each treatment. The treatments for rats were K1 a positive control, K2 a negative control, K3 a healthy control, and P1 treated with leave infused water. The diabetic condition for K1, K2, and P1 was induced with an intravenous injection of 125 mg/kgBW alloxan monohydrate to the rats. After stable diabetic condition, K1 rats were treated with Glibenclamide (0,25 mg/kgBW), K2 rats were untreated, P1 rats were administered with leaves infused water of B. javanica (L) Merr 3 ml/day. K3 rats were uninduced and untreated. The hypoglycemic effect was observed by estimating the fasting blood glucose level of the rats every three days. After 15 days of treatments, P1 rats blood glucose level reduced by the 13,30%, while K1 rats 22,04%. The decrease in blood glucose level of both K1 and P1 rats have not reached the average blood glucose level of healthy rats. The result of the statistical analysis showed the infused extract effect was not significantly differed compared to positive control (P < 0.05).

Background The development of resistant to current antimalarial drugs is a major challenge in achieving malaria elimination status in many countries. Therefore there is a need for new antimalarial drugs. Medicinal plants have always been the major source for the search of new antimalarial drugs. The aim of this study was to screen selected Malaysian medicinal plants for their antiplasmodial properties. Methods Each part of the plants were processed, defatted by hexane and sequentially extracted with dichloromethane, methanol and water. The antiplasmodial activities of 54 plant extracts from 14 species were determined by Plasmodium falciparum Histidine Rich Protein II ELISA technique. In order to determine the selectivity index (SI), all plant extracts demonstrating a good antiplasmodial activity were tested for their cytotoxicity activity against normal Madin-Darby Bovine Kidney (MDBK) cell lines by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results Twenty three extracts derived from Curcuma zedoaria (rhizome), Curcuma aeruginosa (rhizome), Alpinia galanga (rhizome), Morinda elliptica (leaf), Curcuma mangga (rhizome), Elephantopus scaber (leaf), Vitex negundo (leaf), Brucea javanica (leaf, root and seed), Annona muricata (leaf), Cinnamomun iners (leaf) and Vernonia amygdalina (leaf) showed promising antiplasmodial activities against the blood stage chloroquine resistant P. falciparum (EC50

Objective: To assess the safety of Brucea javanica and Cantharidin combined with chemotherapy in treating patients with non-small-cell lung carcinoma. Method: A consecutive cohort of patients with NSCLC were divided into four groups: experimental group A treated with Brucea javanica injection combined with chemotherapy; experimental group B with Cantharidin injection combined with chemotherapy; experimental group C treated with Brucea javanica and Cantharidin injection combined with chemotherapy; and the control group receiving only chemotherapy. After more than two courses of treatment, safety, quality of life and side effects were evaluated. Results: The incidences of myelosuppression in groups A, B and C were lower than that in Control group (p

A new coumarinolignan, cleomiscosin E (I), is isolated together with the known compound cleomiscosin A.

A simple, reliable, and highly sensitive method for the simultaneous determination of aflatoxin B1 , B2 , G1 , G2 in Fructus Bruceae was developed using high-performance liquid chromatography coupled to online postcolumn photochemical derivatization and fluorescence detection. Aflatoxins were first extracted by a methanol/water mixture and then cleaned up with an AflaTest™ immunoaffinity column. Different clean-up and derivatization methods were compared and optimized. The established method was extensively validated to show satisfactory performance of linearity (R(2) ≥ 0.9997), recovery (74.3-100.8%), and precision (RSDs ≤ 2.8%) for the investigated aflatoxins. This proposed method was also applied to 11 F. Bruceae samples and the results showed that 10 out of 11 were contaminated with aflatoxins ranging from 0.26 to 27.52 μg/kg and the occurrence of aflatoxin B1 , the most toxic one, was as high as 91% in all the samples, highlighting the severe contamination and the necessity to set legal limits for aflatoxins in F. Bruceae.

The purpose of this study was to develop and evaluate the supermolecular evodiamine (EVO) loaded water-in-oil nanoemulsions containing brucea javanica oil (NESEB) with enhanced physicochemical and biological characteristics. NESEB was fabricated by applying supermolecular phytosome nanotechnology and nanoemulsification technology together, in addition to using synergistic plant essential oil as a basic composition. Preferred physicochemical and biological characteristics of NESEB were investigated and compared with free EVO and other nanoemulsive EVO carriers. The possible explanations for improved absorption and bioavailability were put forward here. NESEB had high absorption and bioavailability, for example: the absorption rate constants and permeabilities of NESEB in different intestinal segments were 3.65-6.76 times that of free EVO; the relative bioavailability of NESEB to free EVO was 846.97%. NESEB markedly improved the oral bioavailability of EVO, which was most likely due to the increased gastrointestinal absorption. The development of nanoemulsion-based supermolecular EVO nanocarriers provides valuable tactics in insoluble natural antitumor drug delivering.

Today, herb medicines have become the major source for discovery of novel agents in countermining diseases. However, many of them are largely under-explored in pharmacology due to the limitation of current experimental approaches. Therefore, we proposed a computational framework in this study for network understanding of herb pharmacology via rapid identification of putative ingredient-target interactions in human structural proteome level. A marketing anti-cancer herb medicine in China, Yadanzi (Brucea javanica), was chosen for mechanistic study. Total 7,119 ingredient-target interactions were identified for thirteen Yadanzi active ingredients. Among them, about 29.5% were estimated to have better binding affinity than their corresponding marketing drug-target interactions. Further Bioinformatics analyses suggest that simultaneous manipulation of multiple proteins in the MAPK signaling pathway and the phosphorylation process of anti-apoptosis may largely answer for Yadanzi against non-small cell lung cancers. In summary, our strategy provides an efficient however economic solution for systematic understanding of herbs' power.

The ethanol extract ofB. javanicaseed was fractionated with solvents of different polarities and tested for antioxidant activities by several assays including DPPH radical scavenging activity, ferric reducing antioxidant power (FRAP), ferrous ion chelating activity (FCA), and nitric oxide radical scavenging activity (NORSA) along with their polyphenolic contents. Antidiabetic activity was evaluated both in vitro and in vivo using a glycogen phosphorylaseα(GPα) inhibition assay and oral glucose tolerance test (OGTT) in nondiabetic rats. The ethyl acetate fraction (EAF), rich in tannin, exhibited the strongest antioxidant activities to DPPH, FRAP, and NORSA, except for FCA. The EAF also exerted a dose-depended inhibition of GPα(IC50= 0.75 mg/ml). Further evaluation of hypoglycemic effect on OGGT indicated that rats treated with EAF (125 mg/kg bw) showed a 39.91% decrease (P < 0.05) in blood glucose levels at 30 min, and continuous fall (P < 0.05) of 28.89% and 20.29% was observed in the following hours (60 and 90 min) compared to the normal control during OGTT. The EAF was applied to polyamide column chromatography, and the resulting tannin-free fraction was tested for both GPαinhibition and antioxidant (DPPH only) activity. The GPαinhibitory activity was retained, while antioxidant activity was lost (4.6-fold) after tannin removal. These results concluded that the GPαinhibitory activity initially detected was primarily due to the compounds other than tannins, whereas antioxidant activity was mainly due to the tannins.

Three new quassinoid derivatives [desmethyl-brusatol (1), desmethyl- bruceantinoside A (2), and butyl ester (3) of bruceoside D (6)] were isolated from the extract of Brucea javanica. Their structures were elucidated by spectral evidence and chemical transformation to or from known compounds. The three new quassinoid derivatives and related compounds have shown inhibitory effects against TPA-induced Epstein–Barr virus early antigen (EBV-EA) activation.

Several O -acylated derivatives of bruceolide ( 2 ) were synthesized and their anti-malarial activities together with selective toxicities were examined. It was found that 3,15-di- O -acetyl- ( 3c ), 3,15-di- O -propionyl- ( 3d ) and 15- O -propionylbruceolide ( 3b ), as well as bruceine B ( 3a ), exhibited potent anti-malarial activities with high selective toxicities.

Purpose: To investigate the chemical composition and antitumor activity of the petroleum ether extract of the dried ripe fruits of Brucea javanica. Methods: The composition of petroleum ether extract was analyzed by gas chromatography/mass spectrometric (GC/MS) and their antitumor activities were determined by MTT assay. Results: GC/MS spectrometry results indicate that the petroleum ether extract was a mixture of esters, fatty acids, sterides, pregnanones, terpenes, alkaloids, alkenes, alcohols, ketones, aldehydes and other compounds. The results also revealed the significant antitumor activity of the extract with IC50 of 9.14, 12.45, 15.15, 16.13, 22.26, and 27.97 μg/mL against A549, CNE, MCF-7, NCI-H460, HepG2, and KB-3-1 cell lines, respectively. Conclusion: The study establishes the chemical composition and cytotoxic activity of the petroleum ether extract of the plant fruits. There is need for further investigations to isolate more potent compounds and structurally modify the known compounds to retain activity and lower toxicity and thus lead to the possible development of Brucea javanica oil.