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Most antitumor ingredients found in nature have poor solubility. These ingredients are expected to have much better absorption and higher bioavailability than synthetic antitumor agents. Woody oil emulsive nanosystems carrying poorly soluble natural alkaloids were fabricated (evodiamine (EA) carried by fructus bruceae oil-based emulsive nanosystems, or EFEN). Fructus bruceae oil has two excipient-like properties (oil phase and stabilizer) that contribute to the formulation and one drug-like property (antitumor effects) that synergizes with the antitumor effect of EA. The properties of EFEN were compared with free EA, a blank nanoemulsion, an EA-loaded emulsive nanosystem, and a fructus bruceae oil-loaded emulsive nanosystem. For the first time, this suggests that increases in the sensitivity of lung cancer cells to poorly soluble natural alkaloids can be achieved by delivering drugs using woody oil-based emulsive nanosystems. In this study, woody oil-based emulsive nanosystems efficiently deliver poorly soluble natural alkaloids.

Brucea javanica (L.) Merr. is a well-known plant in Chinese System of Medicine. Its fruits and seeds have been reported to possess curative properties against various ailments. The chemical constituents and biological activity of this plant have been an interesting area in plant and chemistry medicine. The aim of this study is to evaluate the antiproliferative effects of the B. javanica extract against a colon cancer cell line and identification of the chemical components derived from the extract. An ethanolic extract from B. javanica fruits was prepared by cold maceration method, subjected to LC-MS profiling to elucidate the composition abbreviated as BJEE. The extract was screened for the cytotoxicity effects on HCT-116 colon cancer cells via MTT and LDH methods. Additionally, AO/PI staining verified apoptosis features in HCT-116 cells through microscopic analysis. ROS, caspase activity, and gene expression has been performed to identify its possible mechanism of actions which contribute to apoptosis. Output data from this study showed BJEE inhibited the cell proliferation of HCT-116 colon cancer cells at IC50 value of 8.9 ± 1.32 (μg mL−1) and significantly increased the levels of caspase-8, 9, and 3/7 in treated cells in comparison to untreated. The changes in expression of caspase genes and some apoptosis genes like Bax and Bcl-2 were confirmed using RT-PCR. Phytochemical analysis by LC-MS identified six major active compounds (bruceine D, isobrucein A, quassimarin, C16 sphinganine, phytosphingosine, and enigmol) in BJEE that may play a key role in cell apoptosis. The current study showed BJEE could be a promising agent for colorectal cancer therapy by significant increase in caspase activity level, and up-regulation of the specific apoptotic genes.

The present study aimed to investigate the effects of ethanol extract from Brucea javanicaseed (EEBJS) on the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the possible molecular signal involved. Firstly, a Matrigel-based in vitro angiogenesis assay demonstrated that EEBJS inhibited the angiogenesis of HUVECs in a dose-dependent manner. Then by using porcine aortic endothelial cells which stably express human PDGFR-beta, we found that the inhibition of angiogenesis was mediated by PDGFR-beta. Taken together, we conclude that EEBJS inhibited the angiogenesis function of the vascular endothelial cells mediated by PDGFR-beta, and postulate that it might contribute to the therapeutic effects of EEBJS on malignant tumors.

Brujavanol E (1), a new quassinoid derivative, along with four known quassinoids (2–5), were isolated from the leaves of Brucea javanica. The chemical structure was elucidated on the basis of extensive spectroscopic analysis. Compound 1 showed significant antimalarial activity (against Plasmodium falciparum strain K1) and cytotoxicity activity against human oral epidermoid carcinoma cancer (KB) and human breast cancer (MCF-7) cell lines with IC50 values 5.54, 2.16, and 1.52 μM, respectively.

Bidens pilosa L. is a troublesome weed that affects the survival and production of crops. Our previous study showed that Brucea javanica (L.) residue has potent herbicidal activity against B. pilosa, and Bruceine D is the main active ingredient in the B. javanica residue. This study showed that Bruceine D significantly inhibited the germination of B. pilosa seeds, especially root hair, and it likewise showed a dose-dependent effect. Transcriptome results showed that phenylpropanoid biosynthesis was inhibited by Bruceine D (10 μg/mL). The expression of PAL, C4H, and 4CL genes were dynamic, whereas genes encoding COMT and POD remained significantly downregulated during Bruceine D treatment. The activities of these enzymes exhibited similar results. At the same time, the contents of several phenylpropanoid biosynthesis metabolites, including flavonoids and lignin, decreased in response to Bruceine D. Our results highlight the use of Bruceine D as a good candidate to develop bioherbicide.

The increasing resistance of malaria to drugs raise the need to new antimalarial agents. Antiplasmodial herbs and their active compounds are the most promising source the new antimalarial agents. This study aimed to identify the medicinal plants with very good in vitro antiplasmodial activities, with half-maximal inhibitory concentration (IC50)≤1μg/ml, and to determine trends in the process of screening their antiplasmodial activities. A total of 58 reports published in the English language were retrieved from the bibliographical databases. Screening and data extraction were performed by two independent reviewers. The herbs were categorized as very good, good, moderate and inactive if the IC50 values were 1-5μg/ml and >5μg/ml respectively. We documented 752 medicinal plants belonging to 254 genera. The majority of the plants were reported from Africa followed by Asia. The traditional use for malaria treatment was the most common reason for the selection of the plants for investigation. About 80% of the plants experimented were reported to be inactive. Among plants identified as having very good to good antiplasmodial crude extracts are Harungana madagascariensis, Quassia africana, and Brucea javanica, while Picrolemma spruce, Aspidosperma vargasi, Aspidosperma desmanthum, and Artemisia annua were reported to have individual compound isolates with very good antiplasmodial activities. In conclusion, the number of plant species assessed so far is still small compared with the stock in nature's plant library. A mechanism of systematically approaching and exploring the untouched plant genera needs to be designed.

Brucea javanica seed oil was exploited as a novel non-edible feedstock for the production of biodiesel in Malaysia. The aim of this study is to optimize transesterification parameters for producing methyl ester from non-edible Brucea javanica seed oil using Response Surface Methodology (RSM) based on Box-Behnken design. Based on the results, optimum operating parameters for transesterification of Brucea javanica oil (BJO) were 65 °C, 1% catalyst and 6:1 methanol to oil ratio with a yield of 94.34%. The results showed that Brucea javanica methyl esters (BJME) fuel properties such as kinematic viscosity 3.556 mm2/s acid value 0.027 mg KOH/g, cloud point 2 °C, pour point 1 °C, flash Point 164 °C, cetane index 51 min and density 871.3 kg/m3 conformed within the range of ASTM D6751 and EN 14214 standard specifications except for oxidation stability at 3.0 h. However, addition of the antioxidant propyl gallate showed high efficiency in improving the oxidative stability of Brucea javanica biodiesel to 70 h.

Brusatol (BR) is one of the main bioactive components derived from Brucea javanica, a medicinal herb historically used in the treatment of dysenteric disorders (also known as ulcerative colitis(UC)). Due to its poor aqueous solubility, a novel brusatol self-microemulsifying drug delivery system (BR-SMEDDS) nanoformulation with smaller size, higher negative zeta potential and drug content, and excellent stability was developed. The appearance of BR-SMEDDS remained clear and transparent, and transmission electron microscopy showed microemulsion droplets to be spherical with homogeneous distribution. Pharmacokinetic parameters indicated that oral bioavailability was greatly improved by BR-SMEDDS as compared with aqueous suspension. Meanwhile, the anti-colitis activity of BR-SMEDDS was evaluated on dextran sodium sulfate (DSS)-induced colitis mice model. The result illustrated that the nano-formation significantly reduced the body weight loss, recovered colon length, decreased disease activity index and microscopic score, regulated immune-inflammatory cytokines, diminished oxidative stress and repressed the colonic expression of myeloid differentiation factor 88 (MyD88), toll-like receptor 4 (TLR4) and nuclear factor kappa B p65 (NF-κB p65) proteins. Our findings demonstrated for the first time that BR could effectively attenuate colonic inflammation in mice, at least partially, via favorable regulation of anti-oxidative and anti-inflammatory status and inhibition of the TLR4-linked NF-κB signaling pathway. The BR nano-formulation was superior to BR suspension and sulphasalazine, in treating experimental UC, and exhibited similar effect with azathioprine, with much smaller dosage. The enhanced anti-UC effect of BR might be intimately associated with the improved pharmacokinetic property by SMEDDS. The developed nano-delivery system might thus be a promising candidate for colitis treatment.

This study was conducted to evaluate the efficacy and possible mechanism of Brucea javanica oil emulsion (BJOE) on cachexia, by observing changes in related indexes in mice with cachexia and identifying the genes responsible based on gene chip analysis. In the BJOE treatment group, body weight loss, tumour growth and metastasis were found obviously inhibited, food and water intake had markedly increased, and survival time was significantly prolonged, as compared to the control group. Moreover, the BJOE witnessed improvement in body weight, prevention of tumour metastasis and overall increase in survival time, as compared to Indometacin (IND, the positive control medicine). It was also found that TNF-α and IL-6 in serum were significantly lower in both groups of BJOE and IND, than in the control group (p .01). Based on the gene expression data, seven and six hub genes of BJOE and IND groups were found in the potential prognostic impacts networks, and three common genes comprising of Nmd3, Bcl2 and Nhp2l1 were screened. Thus, BJOE could reduce tumour growth and effectively alleviate cancer cachexia, due to inhibition of pro-inflammatory cytokines. Nmd3, Bcl2, Nhp2l1 may be important drug targets, establishing the role of BJOE in the treatment of lung cancer induced cachexia.

Ethnopharmacological relevance Brucea javanica is an important traditional medicinal herb used for the treatment of dysentery, malaria, inflammation and cancer in southeast Asia for many years. However, the anti-inflammatory mechanism of Brucea javanica in the treatment of dysentery (also known as ulcerative colitis, UC) has not been fully illuminated. Brucea javanica oil emulsion (BJOE) is the major active and most common application form of Brucea javanica oil (BJO), which has a variety of pharmacological activities. The aim of this study was to investigate the potential anti-inflammatory effect of BJOE and possible mechanism of action on dextran sulfate sodium (DSS)-induced UC in mice. Materials and methods The components of BJOE were determined by gas chromatography-mass spectrometry (GC-MS). Balb/C mice with dextran sulfate sodium (DSS, 30 mg/mL) induced colitis were treated with BJOE (0.5, 1 and 2 g/kg) and two positive drugs (sulfasalazine, SASP, 200 mg/kg; and azathioprine, AZA, 13 mg/kg) once daily by gavage for 7 days. Mice in normal control group and DSS group were orally given the same volume of distilled water and soybean lecithin suspension (0.15 g/kg) respectively. The effects of BJOE on DSS-induced UC were assessed by determination of body weight loss, disease activity index (DAI), colon length, histological analysis, as well as levels of pro-inflammatory cytokines. The mRNA expression of MPO, iNOS and COX-2 in colon tissues was detected by qRT-PCR. In addition, NF-κB p65, p-p65 and IκB-α, p-IκBα protein expression levels in colon tissues were investigated using Western blotting. Results The major components of BJOE were found to be oleic acid (62.68%) and linoleic acid (19.53%) as detected by GC-MS. Our results indicated that BJOE, SASP and AZA showed beneficial effect on DSS-induced colitis in mice, and significantly reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, decreased histological scores, and decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-17 and IFN-γ) as compared with the DSS group. In addition, the mRNA expression of MPO, iNOS and COX-2 induced by DSS treatment was remarkably inhibited by BJOE, SASP or AZA treatments. Furthermore, when compared with DSS-treated mice, the activation of NF-κB was significantly inhibited by AZA and BJOE treatment. Conclusions Our study shows that BJOE possessed appreciable anti-inflammatory effect against murine experimental UC induced by DSS. The protective mechanism of BJOE may involve inhibition of NF-κB signal transduction pathways and subsequent down-regulation of inflammatory mediators. These findings suggest that BJOE might be an efficacious and promising therapeutic approach for the treatment of UC. Our investigation might also provide experimental evidence for the traditional application of Brucea javanica in the treatment of dysentery and might add new dimension to the clinical indications for BJOE.

Background Spinal muscular atrophy (SMA) is a rare neuromuscular disease and a leading genetic cause of infant mortality. SMA is caused primarily by the deletion of the survival motor neuron 1 (SMN1) gene, which leaves the duplicate gene SMN2 as the sole source of SMN protein. The splicing defect (exon 7 skipping) of SMN2 leads to an insufficient amount of SMN protein. Therefore, correcting this SMN2 splicing defect is considered to be a promising approach for the treatment of SMA. Purpose This study aimed to identify active compounds and extracts from plant resources to rescue SMA phenotypes through the correction of SMN2 splicing. Study design Of available plant resources, candidates with SMA-related traditional medicine information were selected for screening using a robust luciferase-based SMN2 splicing reporter. Primary hits were further evaluated for their ability to correct the splicing defect and resultant increase of SMN activity in SMA patient-derived fibroblasts. Confirmed hits were finally tested to determine the beneficial effects on the severe Δ7 SMA mouse. Methods SMN2 splicing was analyzed using a luciferase-based SMN2 splicing reporter and subsequent RT-PCR of SMN2 mRNAs. SMA phenotypes were evaluated by the survival, body weights, and righting reflex of Δ7 SMA mice. Results In a screen of 492 selected plant extracts, we found that Brucea javanica extract and its major constituent Bruceine D have SMN2 splicing-correcting activity. Their ability to correct the splicing defect and the resulting increased SMN activity were further confirmed in SMA fibroblasts. Importantly, both B. javanica and Bruceine D noticeably improved the phenotypic defects, especially muscle function, in SMA mice. Reduced expression of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) contributed to the correction of splicing by B. javanica. Conclusion Our work revealed that B. javanica and Bruceine D correct the SMN2 splicing defect and improve the symptoms of SMA in mice. These resources will provide another possibility for development of a plant-derived SMA drug candidate.

Botanical-based natural products are an important resource for medicinal drug discovery and continue to provide diverse pharmacophores with therapeutic potential against cancer and other human diseases. A prototype Traditional Chinese Medicine (TCM) plant extract library has been established at the US National Cancer Institute, which contains both the organic and aqueous extracts of 132 authenticated medicinal plant species that collectively represent the potential therapeutic contents of most commonly used TCM herbal prescriptions. This library is publicly available in 96- and 384- well plates for high throughput screening across a broad array of biological targets, as well as in larger quantities for isolation of active chemical ingredients. Herein, we present the methodology used to generate the library and the preliminary assessment of the anti-proliferative activity of this crude extract library in NCI-60 human cancer cell lines screen. Particularly, we report the chemical profiling and metabolome comparison analysis of four commonly used TCM plants, namely Brucea javanica, Dioscorea nipponica, Cynanchum atratum, and Salvia miltiorrhiza. Bioassay-guided isolation resulted in the identification of the active compounds, and different extraction methods were compared for their abilities to extract cytotoxic compounds and to concentrate biologically active natural products.

Background Giving Brusein D or Gemcitabine to pancreatic carcinoma cells will re-infect genes that act as tumor suppressor genes. In Brusein D administration there will be activation of p38-MAPK, caspase 9 and caspase 3 as well as inhibition of NF-kB which will stop the synthesis of pancreatic carcinoma DNA so that the cell will carry out cell degradation by apoptosis. In the administration of Gemcitabine, there will be tumor suppressor gene activation, p38-MAPK, which in turn will trigger cell degradation with the mechanism of apoptosis. Methods PANC-1 pancreatic carcinoma cell cultures were divided into three groups. The first group was in control, the second group was treated with three repetitions of the dose of gemcitabine, the third group was treated with three repetitions of the Brusein D dose, then the number of mutant p53 was calculated in each group. Results Mutant p53 expression levels in cultures of pancreatic carcinoma PANC-1 cells in vitro were the least in the Brusein D treatment 2 ug/ml (B 2), which average 12.7%, then Gemcitabine 2 ug/ml (G 2) ) which is an average of 16.7%, followed by Brusein D 1 ug/ml (B 1) which is an average of 22.0%, then followed by Gemcitabine 1 ug/ml (G 1) which is an average of 22.2%, followed by Brusein D 0.5 ug/ml (B 0.5) which is an average of 28.8%, then followed by Gemcitabine 0.5 ug/ml (G 0.5), which is mean average of 29.0%. And the highest level of mutant p53 expression was control, with an average of 51.3%. Conclusions Brusein D ligand from an ethanolic fraction of Makassar Fruit (Brucea javanica (L.) Merr) has the inhibitory potential for mutant p53 expression so that it can be a candidate for the chemotherapeutic agent in cancer with mutations through the p53 pathway.

Background: Vector control is still emphasized on the using of chemical insecticide which can cause death of non-target organisms, pollution and vector resistance. Therefore, natural insecticides/larvicides are an alternative to using chemical insecticides to control the mosquito vector. Methods: Brusatol was isolated from the seeds of Makassar Fruit (Brucea javanica L. Merr). Culex quinquefasciatus larvae were divided into 3 groups, i.e. 6 testing groups and one negative and positive control group. In the negative control group, the larvae were treated with 100 ml aquadest and positive control was treated with temephos 1 ppm. After 24 hours, dead larvae were calculated and the percentage of death was determined. The dead larvae were then examined for morphological changes using a light microscope. Results: The higher of the concentration level of brusatol, the higher number of the death of Cx. quinquefasciatus larvae (P

Cancer management is a worldwide challenge. In addition to effective cancer therapies like chemotherapy, radiotherapy and surgery, treatment based on traditional Chinese medicine (TCM) and combined TCM with western medicine has gradually gained attention in Oriental countries. One potential TCM approach using extracted fatty oils, containing fatty acids which are important active ingredients with a variety of pharmacological activities, makes significant contributions to cancer treatment. The strategies of treating cancer with the fatty oils of TCM were classified into “Fuzheng”, which usually associates with improving immunity, represented by coix seed oil. The other classification is “Quxie”, which relates to inducing apoptosis of cancer cells, and is represented by Brucea javanica oil. Compared with other active substances, the literature about anticancer fatty oils is relatively limited, and most of them focus on the composition and other biological activities without a systematic review. Therefore, based on the theories of “Fuzheng” and “Quxie” in TCM, in this paper, the anticancer effects of fatty oils have been reviewed. The chemical composition, anticancer mechanism, listed drugs, studying dosage form and clinical application of fatty oils have also been discussed. In summary, since there are different types and abundance of fatty oils among botanicals, anticancer effects of fatty oils can be achieved through two TCM theory-based strategies. We hoped that this review paper can reveal the anticancer potential of fatty oils and provide a reference for future related studies.

Systemicity is a desirable property for insecticides. Many phytochemicals show good systemic properties and thus are natural sources of novel systemic insecticidal ingredients. Bruceine D, a quassinoid, was identified in Brucea javanica (L.) Merr. and displayed outstanding systemic properties and excellent antifeedant activity against the diamondback moth (DBM, Plutella xylostella L.), beet armyworm ( Spodoptera exigua Hubner), and cotton leafworm ( Spodoptera litura Fabricius). Its antifeedant effect on third instar larvae of DBM was approximately 6.2-fold stronger than that of azadirachtin. When bruceine D was applied to roots at a concentration of 100 μg/mL for 24 and 48 h, its concentration in flowering Chinese cabbage ( Brassica campestris L. ssp. chinensis var. utiliz Tsen et Lee) leaves was 38.69 μg/g (fresh weight, FW) and 108.45 μg/g (FW), respectively. These concentrations could achieve 93.80% and 96.83% antifeedant effects, which were significantly greater than those of azadirachtin. Similar to azadirachtin, bruceine D also posed a potent growth inhibition effect on insect larvae. After feeding with 20 μg/g bruceine D, no pupae were observed. The results demonstrated that bruceine D is an effective botanical insect antifeedant with outstanding systemic properties, causing potent pest growth inhibitory activity.

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn’s disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.

Brucea javanica (L.) Merr., belonging to Simaroubaceae family, is an evergreen shrub growth widely in Southeast Asia. Traditional medicine in Indonesia and China used B. javanica fruits to treat some diseases, including cancer. This study aimed to investigate cytotoxic activity and anti-migratory effects of B. javanica extract in breast cancer cells in vitro. The dried B. javanica fruits were pulverized and extracted with ethanol 96% for 3x24 hours, then filtered and evaporated. Cytotoxic activity of B. javanica extract was evaluated by MTT assay against 4T1, MCF-7, and NIH-3T3. The cell cycle and apoptosis induction assay on 4T1 and MCF-7 were done using flow cytometry. The inhibitory effect on 4T1 cells migration were observed by scratch wound-healing assay. The results of MTT assay showed that B. javanica extract provided selective cytotoxic activity on 4T1 metastatic breast cancer cells with the IC50 95 µg/ml, with no effect on MCF-7 and NIH-3T3 cells. The extract increased cells population in subG1 but did not affect cells cycle profiles on 4T1 cells. Further results showed that the extract 90 µg/ml induced apoptosis in 4T1 cells. The extract 15, 20, and 30 µg/ml significantly inhibited 4T1 cells migration compared to untreated cells. Thus, B. javanica fruits might be useful for developing an anticancer candidate for the treatment of metastatic breast cancer.

Brucea javanica (L) Merr, locally called “Wali”, is a plant traditionally used to treat diabetes mellitus by local people in Lombok. The people daily consumed the seed to control the blood glucose into normal level. However, the mechanism of action of Wali seed as antidiabetic agent was still unclear. Hence, in this study we investigate the proposed mechanism of action of Wali seed suspensed and ethanolic extract trough measuring the glycogen content in liver and muscles and observing the pancreatic histology of diabetic rats. Wali seed extract (dose 20 and 30 mg/kg BW) and suspense (25 and 50 mg/kg BW) have comparable antidiabetic activity with glibenclamide. Treatments of Wali seed extract and suspense showed dramatically higher glycogen level both in liver and muscles than all controls. Treatment with glibenclamide and Wali seed extract and suspense the pancreas to normal architecture, regeneration of β-cell and enhanced morphology of the β- cells in the islets of Langerhans. The proposed mechanism of action of Wali seed extract and suspense is by converting blood glucose to glycogen storage trough glycogenesis and by recovering the islets of Langerhans of pancreas damage.Brucea javanica (L) Merr, locally called “Wali”, is a plant traditionally used to treat diabetes mellitus by local people in Lombok. The people daily consumed the seed to control the blood glucose into normal level. However, the mechanism of action of Wali seed as antidiabetic agent was still unclear. Hence, in this study we investigate the proposed mechanism of action of Wali seed suspensed and ethanolic extract trough measuring the glycogen content in liver and muscles and observing the pancreatic histology of diabetic rats. Wali seed extract (dose 20 and 30 mg/kg BW) and suspense (25 and 50 mg/kg BW) have comparable antidiabetic activity with glibenclamide. Treatments of Wali seed extract and suspense showed dramatically higher glycogen level both in liver and muscles than all controls. Treatment with glibenclamide and Wali seed extract and suspense the pancreas to normal architecture, regeneration of β-cell and enhanced morphology of the β- cells in the islets of Langerhans. The proposed mechanism of ...

Free radicals are an atom or molecule that has unpaired electrons which make them reactive and unstable that caused various damages to the cells. The natural antioxidants are very needed to inhibit free radicals. Brucea javanica (L) Merr, known as “Wali”, is one of the local plants that potential as a natural antioxidants due to the content of phenolic compound. The aim of this study was to determine the antioxidant activity by using DPPH method and the total phenolic content in the ethanol extract of Wali seeds derived from maceration and soxhletation. The results of antioxidant activity measurements showed that ethanol extract of Wali seeds derived from maceration had a strong activity (IC50 of 64,703 ppm), while the extract from soxhletation had a moderate activity (IC50 of 121,739 ppm). The total phenolic compounds responsible to the antioxidant activity of ethanol extract of Wali seeds derived from maceration and soxhletation were 4.946,35 mg EAG/100g and 3.830,72 mg EAG/100g, respectively. The ethanol extract of Wali seeds derived from maceration has higher antioxidant activity and total phenolic content than the extract from soxhletation with a significant different (p

We report pH-responsive liquid crystalline lipid nanoparticles, which are dual-loaded by Brucea javanica oil (BJO) and doxorubicin hydrochloride (DOX) and display a pH-induced inverted hexagonal (pH = 7.4) to cubic (pH = 6.8) to emulsified microemulsion (pH = 5.3) phase transition with a therapeutic application in cancer inhibition. BJO is a traditional herbal medicine that strongly inhibits the proliferation and metastasis of various cancers. Doxorubicin is an antitumor drug, which prevents DNA replication and hampers protein synthesis through intercalation between the base pairs of the DNA helices. Its dose-dependent cardiotoxicity imposes the need for safe delivery carriers. Here, pH-induced changes in the structural and interfacial properties of designed multicomponent drug delivery (monoolein-oleic acid-BJO-DOX) systems are determined by synchrotron small-angle X-ray scattering and the Langmuir film balance technique. The nanocarrier assemblies display good physical stability in the studied pH range and adequate particle sizes and ζ-potentials. Their interaction with model lipid membrane interfaces is enhanced under acidic pH conditions, which mimic the microenvironment around tumor cells. In vitro cytotoxicity and apoptosis studies with BJO-DOX dual-loaded pH-switchable liquid crystalline nanoparticles are performed on the human breast cancer Michigan Cancer Foundation-7 (MCF-7) cell line and MCF-7 cells with doxorubicin resistance (MCF-7/DOX), respectively. The obtained pH-sensitive nanomedicines exhibit enhanced antitumor efficacy. The performed preliminary studies suggest a potential reversal of the resistance of the MCF-7/DOX cells to DOX. These results highlight the necessity for further understanding the link between the established pH-dependent drug release profiles of the nanocarriers and the role of their pH-switchable inverted hexagonal, bicontinuous cubic, and emulsified microemulsion inner organizations for therapeutic outcomes.

Bruce javanica (L) Merr is a medicinally important plant, commonly known as Wali. The extract of its seed has various secondary metabolites responsible for its pharmacological properties. Unfortunately, the recent method of extraction lacks in the percentage of the yield and has disadvantages to the environment. Enzymatic extraction of bioactive compounds is a potential alternative. In this research, we use some crude natural enzymes that are amylase, protease (bromelain), and cellulase isolated from corn kernels, pineapple fruit, and beef rumen fluid, respectively. The aim of this research was to determine the effectiveness of crude natural enzymes for the extraction of metabolite compounds in wali seed comparing with the solvent extraction method. For each of one gram of wali seed powder was extracted by using ultrasonic-assisted extraction (UAE) method with solvent of (1) methanol; (2) ethanol 96%; (3) bromelain; (4) amylase; (5) cellulase; (6) bromelain+amylase; (7) bromelain+cellulase; (8) amylase+cellulase; (9) amylase+bromelain+cellulase. The extracts of (1) and (2) were then evaporated; while extracts of (3) to (9) were freeze-dried. The appearance of extracts (1) and (2) were bright-yellow viscous liquid; while extracts (3) to (9) were solid-milky powder. Cellulase increases the extraction yield up to 40% and 22% in comparison with methanol and ethanol, respectively. The semiquantitative analysis showed that methanol extracts the metabolites with the highest concentration but has the lowest amount of yield extract. However, cellulase showed the highest ability to extract metabolites tested. The flavonoid content extracted using cellulase enzymes resulted in an increase of 273% and 170% in comparison with methanol and ethanol, respectively. Thus, the use of crude cellulase enzyme isolated from beef rumen fluid is the best choice to extract wali seed among other enzymes and solvents used.

Brucea javanica oil (BJO), one of the main products of Brucea javanica, has been widely used in treating different kinds of malignant tumors. Quassinoids are the major category of anticancer phytochemicals of B. javanica. However, current researches on the anti-cancer effect of BJO mainly focused on oleic acid and linoleic acid, the common major components of dietary edible oils, essential and characteristic components of B. javanica like quassinoids potentially involved remained unexplored. In the current investigation, we developed an efficient HPLC method to detect brusatol, a characteristic quassinoid, and comparatively scrutinized the anti-hepatocellular carcinoma (anti-HCC) effect of BJO, brusatol-free BJO (BF-BJO), and brusatol-enriched BJO (BE-BJO) against hepatoma 22 (H22) in mice. High-performance liquid chromatography (HPLC) was utilized to identify the components in BJO. BE-BJO was extracted with 95 % ethanol. The anti-tumor effect of BJO, BF-BJO and BE-BJO was comparatively investigated, and the potential underlying mechanism was explored in H22 ascites tumor-bearing mice. The results indicated that BJO and BE-BJO significantly prolonged the survival time of H22 ascites tumor-bearing mice, while BF-BJO exhibited no obvious effect. BJO and BE-BJO exhibited pronounced anti-HCC activity by suppressing the growth of implanted hepatoma H22 in mice, including ascending weight, abdominal circumference, ascites volume and cancer cell viability, with a relatively wide margin of safety. BJO and BE-BJO significantly induced H22 cell apoptosis by upregulating the miRNA-29b gene level and p53 expression. Furthermore, BJO and BE-BJO treatment substantially downregulated Bcl-2 and mitochondrial Cytochrome C protein expression, and upregulated expression levels of Bax, Bad, cytosol Cytochrome C, caspase-3 (cleaved), caspase‑9 (cleaved), PARP and PARP (cleaved) to induce H22 cells apoptosis. Brusatol was detected in BJO and found to be one of its major active anti-HCC components, rather than fatty acids including oleic acid and linoleic acid. The anti-HCC effect of BJO and BE-BJO was intimately associated with the activation of miRNA-29b, p53-associated apoptosis and mitochondrial-related pathways. Our study gained novel insight into the material basis of BJO in the treatment of HCC, and laid a foundation for a novel specific standard for the quality evaluation of BJO and its commercial products in terms of its anti-cancer application.

Brucea javanica oil (BJO), a traditional herbal medicine extracted from the seeds of B. javanica, has been clinically used to treat non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in combination with chemotherapy or radiotherapy in China. However, how BJO exerts this antitumor effect is still largely unknown. Here, effects of BJO on the growth of NSCLC and SCLC cell lines were investigated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenytetrazolium Bromide (MTT) assay, and the results showed that BJO inhibited the proliferation of A549 cells (NSCLC) and H446 cells (SCLC). Further studies revealed that BJO induced G0/G1 arrest partly via regulating p53 and cyclin D1 in these two cell lines. BJO also has pro-apoptotic effect on H446 and A549 cells through mitochondria/caspase-mediated pathway, which was initiated by the accumulation of intracellular reactive oxygen species (ROS). These findings thus revealed the molecular mechanisms underlying the antitumor effect of BJO on SCLC and NSCLC, which may benefit the further clinical application of BJO.

This study was aimed at preparing a stable nanostructure lipid carriers for Brucea javanica oil (BJO/NLCs) using the high-pressure homogenization (HPH) method. The obtained BJO/NLCs exhibited a particle size of approximately 180 nm and were quite stable during 30 days of storage. The entrapment efficiency (EE) and drug loading (DL) of BJO/NLCs were good, with values of up to 99.2% and 10.4%, respectively. The polydispersity index (PDI) and zeta potential values of BJO/NLCs were 0.17 and −31.2 mV, respectively. BJO/NLCs exhibited spherical or elongated particles when viewed by transmission electron microscopy (TEM). Small-angle X-ray scattering (SAXS) further confirmed that the internal structures of blank NLCs and BJO/NLCs were arranged into lamellar phases. Anti-tumor activity was studied using the MTT assay; the BJO/NLCs showed improved cytotoxicity to A549 cells. Taken together, these results indicate that this newly designed BJO/NLCs delivery system has the potential to exhibit improved BJO bioavailability.

Fatty acids are important nutritional substances and metabolites in living organisms. These acids are abundant in Chinese herbs, such as Brucea javanica, Notopterygium forbesii, Isatis tinctoria, Astragalus membranaceus, and Aconitum szechenyianum. This review illustrates the types of fatty acids and their significant roles in the human body. Many analytical methods are used for the qualitative and quantitative evaluation of fatty acids. Some of the methods used to analyze fatty acids in more than 30 kinds of plants, drugs, and other samples are presented in this paper. These analytical methods include gas chromatography, liquid chromatography, near-infrared spectroscopy, and NMR spectroscopy. The advantages and disadvantages of these techniques are described and compared. This review provides a valuable reference for establishing methods for fatty acid determination.

Two new quassinoids, brujavanol A (1) and brujavanol B (2), along with five known quassinoids (3-7), were isolated from the roots of Brucea javanica. Their structures were elucidated by spectroscopic methods. The antimalarial and cytotoxic activities of the isolated compounds were also assessed. Compounds 1 and 2 exhibited significant in vitro cytotoxicity against human oral cavity cancer (KB) cells with IC50 values of 1.30 and 2.36 μg/ml, respectively, whereas compound 3 showed excellent antiplasmodial activity against the Plasmodium falciparum strains, K1 (IC50 = 0.58 μg/ml).