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Brucea javanica (L.) Merr. is a medicinal herb used in China for the prevention and treatment of diseases such as cancer and malaria. Brusatol was isolated from the seeds of Brucea javanica (L.) Merr, brusatol has a wide range of pharmacological effects, including anti-inflammation and anti-cancer effects.Renal cell carcinoma is one of the most common urinary system tumours and seriously threatens the lives of patients. We aimed to study the mechanism by which brusatol regulates the growth of renal cancer cells through the PTEN/PI3K/AKT signalling pathway.We chose the A498, ACHN, and OSRC-2 cell lines as experimental models. After intervention with brusatol, CCK-8 experiments and plate cloning experiments were used to detect the cell proliferation ability; flow cytometry was used to detect the cell apoptosis rate; scratch and transwell invasion assays were used to detect the cell migration and invasion ability; qRT-PCR and Western blotting was used to detect PTEN, p-PI3K/PI3K, p-AKT/AKT, Bax, Bcl2, E-cadherin, N-cadherin, and vimentin relative expression. Then, we knocked down the PTEN gene in the three cell lines and again tested the proliferation, apoptosis, migration, and invasion capabilities of each group of cells.Brusatol significantly inhibited the proliferation, migration and invasion and increased the rate of apoptosis of the A498, ACHN, and OSRC-2 cell lines, and brusatol significantly increased the expression of PTEN mRNA and protein, and inhibited the expression of p-PI3K and p-AKT. Moreover, knockdown of PTEN significantly reduced the inhibitory effect of brusatol on the growth of renal cancer cells.Our research results show that brusatol has an effective inhibitory effect on the growth of A498, ACHN, and OSRC-2 renal cancer cell lines, and this effect is likely to be produced by regulating the PTEN/PI3K/AKT signalling pathway.

Ethnopharmacological relevance The seeds of Brucea javanica and its aqueous decoction is a traditional medicine consumed by diabetic patients in Malaysia. The daily consumption of B. javanica seeds and it's aqueous decoction causes much concern as the quassinoids and its glycosides from the seeds exhibited various pharmacological activity at low doses. Aims of study The aim of the present study is to evaluate the repeated dose toxicity of the standardized aqueous extract administered daily for 30 days through oral administration at its effective hypoglycemia doses. Materials and methods The seeds were dried, ground and extracted in deionized water. A HPLC-photodiode array method was developed and validated for the standardization of both the hypoglycemia agents, namely bruceine D and E in aqueous extract. Both normoglycemia and streptozotocin (STZ)-induced diabetic rats were fed orally with 15, 30 and 60 mg/kg body weight of standardized aqueous extract. The blood glucose was measured at 0–8 h. In repeated dose toxicity, similar doses were administered orally to rats for 30 days. At the end of 30 days, the blood was withdrawn and subjected to biochemical and haematology analysis while organs were harvested for histology analysis. Results Oral administration of standardized aqueous extract exhibited a dose-response relationship in both the normoglycemia and STZ-induced diabetic rats. Daily oral administration of 15, 30 and 60 mg/kg standardized aqueous extract for 30 days to rats did not show signs to toxicity in its biochemical, haematology and histology analysis. Conclusion In conclusion, although the seeds were reported to contain compounds with various pharmacological activity, the daily oral administration to rats for 30 days do not showed signs of toxicity at its effective hypoglycemia doses.

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.

Ethnopharmacological relevance The seeds of Brucea javanica (L.) Merr. (Yadanzi in Chinese) have been used for the treatment of inflammation, dysentery, malaria, and cancer in Chinese traditional medicine. However, the anti-inflammatory mechanism of Brucea javanica has not been fully elucidated. This study examined the anti-inflammatory activity of ethyl acetate fraction of the seeds of Brucea javanica (EA-BJ) in vitro and in vivo. Materials and methods The anti-inflammatory activity of EA-BJ and its ability to modulate the production of NO, PGE2, TNF-α, IL-1β, IL-6 and IL-10 inflammatory mediators in lipopolysaccharide-activated RAW 264.7 macrophage were evaluated. Moreover, the anti-inflammatory activity of EA-BJ was also in vivo assayed by carrageenan induced paw edema in mice. Results In vitro assays showed remarkable anti-inflammatory activity of EA-BJ, through the inhibition of production of NO, PGE2, TNF-α, IL-1β and IL-6 inflammatory mediators and induction of production of IL-10 anti-inflammatory cytokine. In vivo assays showed anti-inflammatory activity for decrement of the paw edema in carrageenan induced paw edema test. Conclusion The results obtained in vitro and in vivo showed that possible anti-inflammatory effects of EA-BJ may be attributed to inhibition pro-inflammatory mediators production, NO, PGE2, TNF-α, IL-1β and IL-6 and to increase production of IL-10 anti-inflammatory cytokine. The seeds of Brucea javanica may thus prove beneficial in the treatment of inflammatory diseases.

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 .

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.

The activities of n-hexane, dichloromethane and methanol extracts from five anti-diarrheic Thai medicinal plants, Acacia catechu (Fabaceae) resin, Amaranthus spinosus (Amaranthaceae) whole plant, Brucea javanica (Simaroubaceae) seed, Piper longum (Piperaceae) fruit and Quercus infectoria (Fagaceae) nut gall were tested against the in vitro growth of fresh isolates of the intestinal protozoan parasite, Blastocystis hominis. The extracts at concentrations that ranged from 62.5 to 2000 microg/mL, were incubated with several isolates of Blastocystis hominis for 48 h. The activities were classified as killed, inhibited, moderately inhibited and not-inhibited. Dichloromethane and methanol extracts from the Brucea javanica seed and a methanol extract from Quercus infectoria nut gall showed the highest activity. At a concentration of 2000 microg/mL, the three extracts killed 82, 75 and 67% of the Blastocystis hominis samples tested and inhibited 94, 100 and 76% of them, respectively. Metronidazole, used as a reference antiprotozoan drug, at a concentration of 40 microg/mL, killed 97% of the Blastocystis hominis isolates and inhibited all samples tested at concentrations that ranged from 1.25 to 20 microg/mL.

This is the first inn vitro study on the activity of 20 kinds of crude extracts of traditional Chinese medicine (TCM) on the intestinal parasite, Blastocystis hominis using the criteria of living cell count (LCC) and living cell rate (LCR). LCC and LCR were applied as observation indicators, the former as a fixed-quantity and the latter as a fixed-quality method. LCR calculated percentage rate of living cells using eosin-brilliant cresyl blue staining which could differentiate between living cells and dying or dead cells. There were five extracts with no inhibitory activity, thirteen with moderate inhibition and two with high inhibition. The crude extracts of Coptis chinensis (CC) and Brucea javanica (BJ) were found to be most active against B. hominis. The active concentration of CC was 100 micrograms/ml. The active concentration of BJ was 500 micrograms/ml. The active concentration of metronidazole (MD) was 10 micrograms/ml and this was taken as an active standard drug for B. hominis.