[English Name] | Java Brucea Fruit | |
[Chinese Name] | 鸦胆子 | |
[Pinying Name] | Yadanzi | |
[Latin Name] | Bruceae Fructus | |
[Genera] | Simaroubaceae | |
[Efficacy] | jiedushachongyao | |
[Pictures] | Plant picture | Drug picture |
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[Ecology] | It grows in the lime mountain open forest at the altitude between 950 to 1000 metres. | |
[Chemical composition] | ||
[Pharmacological activities] |
1 Anti-tumor effect: The Brucea water injection and oil in water the tendons emulsion can significantly inhibit mouse spermatogonial cell mitosis. Intravenous emulsion of Brucea oil in water can inhibit Ehrlich ascites carcinoma and ascites hepatoma cells in vitro; in the overall test, intravenous emulsion of oil in water has a good anti-cancer effect on Ehrlich ascites carcinoma, localized drug delivery also has a certain effect on sarcoma S37, S180 sarcoma [1]. Intraperitoneal injection of Brucea emulsion can inhibit the entity type in mice, ascites of hepatocellular carcinoma and rat sarcoma W256. In combination with cyclophosphamide, it can eliminate cyclophosphamide-induced leukopenia. After 1 hour of contact between 5% Brucea emulsion abd Ehrlich ascites tumor cells, the cell killing rate reaches 80%, after 4 hours up to 100% [2]. Brucea oil emulsion intervention or adding embolic agent has anti-cancer effects on N-methyl nitrosourea (MNU)-induced rat bladder tumor [3]. Brucea oil emulsion can significantly inhibit the growth of human bladder cancer cell line BIU-87 cells, it can directly destroy the bladder cancer cell membrane, mitochondrial membrane, endoplasmic reticulum and nuclear membrane and other membrane systems, it can lead to the denaturation and necrosis of bladder cancer cell [4]. Brucea oil can effectively inhibit the in vitro proliferation of human gastric cancer SGC-7901 cell [5,6]. Brucea oil emulsion, the oleic acid emulsion have significantly damaging effects on the structure of mouse Ehrlich ascites tumor cells in vitro [7]. Brucea oil emulsion and oleic acid contained in the oil in vitro can inhibit the incorporation of radioisotope tritium - thymine deoxy nucleoside (3H-TdR) into Ehrlich ascites cancer cell deoxyribonucleic acid (DNA), indicating that it can inhibit cancer DNA synthesis, and this role strengthens as the increase of concentration [8-10]. The Brucea flooding agent and the chloroform extracts of flooding agent can inhibit nasopharyngeal carcinoma KB cells in vitro [11]. Brucea oil emulsion has a certain damage or inhibitory effects on Ehrlich ascites carcinoma DNA synthesis phase (S), DNA synthesis late (G2) and split the suspension period (G0) phase cells, suggesting that it may belong to the non-specific cell cycle drugs [12]. Topical treatment of Brucea Jen paste agent, water agent or Brucea oil on skin cancer in mice induced by methylcholanthrene vinegar ketone and papilloma, can make cancer cells degeneration and necrosis, the efficacy of paste is the best, water agent and oil is poor. But it also has a similar effect on normal skin [13]. Daily intraperitoneal injection of crow gall Pavilion 0.25~1mg/kg on mice has significant effects on lymphocytic leukemia P388; daily injections of the Brucea bitter glycosides A6mg/kg or Brucea bitter alcohol 125~250μg/kg are also effective [14]. Daily application of crow gall kiosk or the the Brucea glycosides P may prolong the survival time of murine lymphocytic leukemia P388 [15]. The Brucea glycosides A, C, F and G all have anti-tumor effects [16], the Brucea glucoside K, I and L have inhibitory effect on mouse leukemia P388 cells [17], the aglycone of Brucea glycosides N and O can control the growth of murine leukemia P388 [18]. The Brucea glycosides A-G and L-I have anti-leukemia effects on mouse lymphocytic leukemia P388 [19]. Lily lignans A contained in Brucea can against the P388 lymphocytic leukemia cells in vitro [20]. The half effective dose (ED 50)of crow gall kiosk of cytotoxicity on the in vitro cultured human nasopharyngeal epidermoid carcinoma KB cells is 0.008μg/ml [21]. Anti-tumor mechanism of action: Brucea can not significantly increase the adenosine monophosphate (cAMP) content in the mouse liver cancer cell, indicating that it does not inhibit the proliferation of cancer cells by increasing the cAMP content thus playing an anti-cancer effect [2]. Crow gall Pavilion, Brucea bitter element D and E, Brucea bitter glycosides A and Brucea bitter alcohol can significantly inhibit the P388 lymphocytic leukemia ribonucleic acid (RNA) and protein synthesis; but in the overall test of P388 leukemia in mice, the inhibition of drug DNA synthesis seems to have a more direct relationship between its anti-tumor effect; in vitro, Brucea bitter alcohol, Brucea gentiopicroside A have marginal inhibition on the activity of received 10 days P388 cell DNA polymerase, RNA polymerase, thymidylate synthase, dihydrofolate reductase, phosphoribosyl pyrophosphate aminotransferase and organizations protease; in the overall experiment they also have similar inhibitory effects and can increase cAMP concentration, these effects are positively correlated with the anti-tumor effect of each drug. In the overall test, Brucea bitter alcohol has a strong inhibitory effect on purine synthesis. The inhibition point is mainly ribose pyrophosphate aminotransferase [14]. The Brucea bitter alcohol can significantly inhibit the hexokinase, phosphofructokinase, malate dehydrogenase and succinate dehydrogenase of P388 cells, in the overall experiment it can significantly inhibit the mitochondrial oxidative phosphorylation and substrate phosphorylation with the substance of succinate and α-ketoglutaric acid. The Brucea bitter alcohol can significantly increase the cAMP content of P388 cells. The inhibition of Brucea gentiopicroside A crow gall Pavilion on oxidative phosphorylation in P388 cells is similiar with that of Brucea bitter alcohol [22]. The impact of Brucea oil emulsion on cultured human bladder carcinoma cell line of BIU-87 cell growth, organizational structure and cell cycle is mainly the prevent of BIU-87 cells from G0/G1 to S phase progress [4]. Brucea oil emulsion has obvious destruction on BIU-87 cells, and shows a dose and time dependent, from the point of incorporation inhibition rate of 3H-TdR, the cancer cell DNA synthesis of drug group is slowed down, the strong nucleic acid synthesis and metabolism of cancer cells are reduced, making the incorporation inhibition rate of 3H-TdR also increase with the increasing drug concentration, which also proves that the growth inhibition of Brucea oil emulsion on BIU-87 cancer cell is mainly through the inhibition of DNA synthesis [23]. The impact of Brucea oil emulsion on the granulosa cells of human renal cancer cell line GRC-1 cell cycle is also by inhibiting the S phase DNA synthesis [24]. By flow cytometry to analyze the cell cycle changes before and after the drug effects of renal cell carcinoma, finding that Brucea oil emulsion can prevent the progress of the GRC-1 and RLC-310 cells from G0/G1 to S phase, and inhibit DNA synthesis [25]. The mechanism of Brucea oil emulsion on prostate cancer cells is that the enter of a large number of Brucea oil emulsion particles into cells within the occurrence of fatty degeneration, and via the particles causes direct damage of plasma membrane, mitochondria, and rough endoplasmic reticulum and other cells [26]. In agarose gel electrophoresis detection, Brucea oil emulsion shows a clear DNA ladder, from the perspective of morphology and biochemical, this proves that Brucea oil emulsion can induce apoptosis of tumor cells, which in a dose-dependent manner [27]. Brucea oil emulsion prevents the BIU-87 bladder cancer cells from G0/G1 cycle into S phase, and induce apoptosis of people BIU-87 bladder cancer cell; and one of the mechanisms of Brucea oil emulsion against cancer is inducing apoptosis of BIU -87 bladder cancer cell [28]. In vitro, Brucea bitter element A and crow gall Pavilion can inhibit the mice TLX5 lymphoma cells from uptake of 3H-TdR, with the 50% infective dose (ID 50) of 0.31μg/kg and 0.003μg/mg, respectively [29]. 2 Antimalarial effect: Brucea benevolence oral administration or intramuscular injection of its crude extract both have a significant antimalarial effect, so that the malaria parasite in the blood is reduced and even negative [30]. Intramuscular injection of Brucea benevolence decoction anti-chicken malaria role, with the minimum effective dose of 0.02g (crude drug)/kg, the minimum effective amount of extract is 0.0025g/kg. Brucea leaves also have antimalarial effects [31]. The half inhibitory rate (IC50) of Brucea flooding agents and chloroform extracts of flooding agents on Plasmodium falciparum in vitro are 0.42μg/ml and 0.006μg/ml, respectively; ED50 of malaria parasite infected mice are 500mg/kg and 7.4mg/kg, respectively; ED50 of chloroquine diphosphate is 1.52mg/kg [32]. Brucea chloroform extracts has the strongest inhibitory effect on Plasmodium falciparum in vitro, with the minimum inhibitory concentration (MIC) 16.48μg/ml, water extract is weaker, with the MIC 19.48μg/ml. Three kinds of active ingredients isolated from the chloroform extracts, Brucea bitter element A, C, and Brucea bitter Su B hydrates, the role of C is strongest, its inhibition of the uptake of Plasmodium falciparum of [3H] hypoxanthine is stronger than that of mefloquine, these three components are still effective the malaria parasite resistance to mefloquine [33]. In vitro, Brucea bitter alcohol has a very strong inhibition on aiti-chloroquine Plasmodium falciparum, the Brucea bitter glycosides A is not active, which proving that the C15 ester part is relevant to the strengthen of anti-malarial effects of lignin-like substances [34]. In vitro, with the uptake of [3H] hypoxanthine of anti-chloroquine Plasmodium falciparum as an indicator, the IC50 values (μg/ml) of the active ingredients of Brucea are as follows: crow gall Pavilion 0.0008, crow gall kiosk alcohol 0.002, Brucea bitter elements A0.011, B0.011, C0.005, D0.015, dehydrogenase Brucea bitter elements A0.046, Brucea bitter alcohol 0.003, Brucea glycosides A0.031, F5.00, I22.04, diphosphate chloroquine 0.210. In the overall trial, ED50 and 90% effective dose (ED90) [mg/kg per day] of parasitemia in malaria parasite (Plasmodium berghei) infected mice are as follows: Brucea bitter elements A3.36 and 26.72, Brucea bitter element B0.90 and 2.82, Brucea bitter alcohol 1.27 and 3.03, Brucea bitter element D2.79 and 8.19 [35]. The role against parasite of Brucea and its active ingredients in vitro are stronger than that of nasopharyngeal carcinoma KB cells, and their anti-malarial effects are not caused by cytotoxicity [32, 36]. 3 Anti-amoeba effect: Adding Oil-free Brucea flooding fluid and ether extract into infection stool, can kill the amoeba [37]. Brucea benevolence aqueous extracts (1%) can kill the amoeba in vitro, 1: 1000 aqueous solution can inhibit its growth, Brucea benevolence oral administration or enema infusion has a positive effect on amoebic dysentery [38]. The Brucea butanol extract, bitter lignin, Brucea bitter element C and crow gall Pavilion show significant inhibitory effect on Entamoeba histolytica protozoa, the IC50 are 8.25μg/ml, 0.50μg/ml 10μg and 0.35μg/ml, respectively. Make the simultaneous determination of IC50 of uptake of 3H-TdR in guinea pig keratinocytes formation cells as the inhibition of normal cells, the IC50 of bitter lignin, Brucea bitter element C and crow gall kiosks are 66μg/ml, 18μg/ml and 0.04μg/ml, respectively. The ratio of IC50 (anti-normal cells) / IC50 (anti-amoebic) among these three are 132, 1.8 and 0.1, respectively, and the function of bitter lignin most valuable [39]. The IC50 of crow gall pavilion inhibition of Entamoeba histolytica protozoan in vitro is 0.019μg/ml [40]. 4 The impact on immune function: Brucea oil can promote rat spleen weight, the number of hemolytic plaque peritoneal macrophage phagocytosis and bone marrow hematopoietic stem cell proliferation caused by 60Co irradiation [1]. Intravenous treatment of Brucea emulsion on esophageal cancer, gastric cancer, colorectal cancer and breast cancer patients, has no significant effect on the T-cell esterase staining, suggesting that it has no inhibitory effect on cellular immunity, humoral immunity indicates that immunoglobulin G (IgG) M, immunoglobulin M (IgM) fluctuations in the normal range, and the immunoglobulin A (IgA) is higher than normal value, which may promote the improvement of infection resistance of patients with advanced tumors [41]. Brucea emulsions in vitro can not enhance the formation of E rosette, nor promote the transformation of lymphocyte, showing that the in vivo and in vitro effects of Brucea may be inconsistent [42]. 5 Other: Brucea crude extracts can get rid of dog intestinal nematodes and tapeworms [43], and whipworm and roundworm as well [44]. 5%~10% Brucea cold immersion can kill mosquito larvae, its stems and leaves into the water tank are also effective [45]. Brucea glycosides A, C, F, G have antiviral effects [20]. Continuous gavage Brucea oil emulsion granules with 1.4, 2.8g (the Brucea of oil)/kg per day to mice for three days, can significantly inhibit the formation of gastric ulcer by pyloric ligation in rats; intragastrical injection of 1.2g (Brucea oil)/kg per day for 3 days, can significant inhibit aspirin induced formation of mouse gastric ulcer; intragastrical injection of 0.6, 1.8g (Brucea of oil)/kg per day for 3 days, can significant inhibit of water beam stress gastric ulcer in mice; intragastrical injection of 0.5, 1.0g (Brucea Oil)/kg for 9 days can significant inhibit the formation of rat acetic acid chronic gastric ulcer; intragastrical injection of 0.5, 1.0g (Brucea Oil)/kg for three months, has a significant inhibitory effect on ammonia induced chronic atrophic gastritis [46]. 6 In vivo process: After intravenous injection of oleic acid intravenous milk on mice and rabbits, the changes of pharmacokinetics are shown for the two-bedroom open model. After intravenous injection, the half-life of rabbits distribution phase is 0.4 hours, the half-life of elimination phase is 12.6 hours. The highest distribution in mice is spleen, followed by liver, lung, kidney, heart, etc., drug concentrations in brain are also high, indicating that oleic acid can pass through the blood-brain barrier. Drugs can discharge through feces, urine, with 24 hours total discharge of 46.46% [47]. |
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[Traditional usage] |
1. Wart 2. Corn, and callus 3. Veneral toxic gonorrhea with heat 4. Dysentery 5. Dysentery with blood in the stool, and hematochezia of heat pattern 6. dysentery in a long time with stench purulent blood, and deficiency of lower jiao, exhaustion due to qi deficiency 7. Malaria 8. Schistosomiasis in the early stage 9. Hemorrhoid 10. Trichomonas vaginitis |
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