Antitumor effects and chemical compositions of Eupolyphaga sinensis Walker ethanol extract.

Eupolyphaga sinensis Walker popularly known as "preferred drug to regulate blood flow" are traditionally used in folk medicine in the treatment of ecchymoma, posttraumatic wound, hepatic fibrosis and tumor. To characterize chemical compositions and to evaluate the antitumor and immunomodulatory of Eupolyphaga sinensis Walker ethanol extract (ESEE) in hepatocarcinoma H(22) bearing mice. ESEE was obtained by ethanol reflux extraction and analyzed by gas chromatography-mass spectrometry (GC-MS) after methylation. ICR mice were treated with ESEE for 14 consecutive days at doses of 31mg/kg (low-dose), 62mg/kg (mid-dose) and 124mg/kg (high-dose) after H(22) tumor cells were implanted. At the end of the experiments, the tumor weight of each mouse was measured. Levels of serum TNF-α and IFN-γ was assayed by ELISA. Protein expressions of Bax, Bcl-2 and caspases-3 were detected by immunohistochemistry. Chemical analysis revealed the presence of 6 components that account for 97.55% of fatty acids, indicating the occurrence of saturated and polyunsaturated fatty acids. Oral administration of ESEE could inhibit tumor growth, promote Th1 type cytokine productions (TNF-α and IFN-γ) and induce apoptosis of hepatocarcinoma via increase of Bax/Bcl-2 ratio and activation of caspases-3. Oral administration of ESEE in a dosage of 6.2g/kg did not lead to toxic effects in mice. ESEE was effective in inhibiting tumor growth in vivo and could also serve as immunoadjuvant for tumor therapy.

Ge GF ，Yu CH ，Yu B ，Shen ZH ，Zhang DL ，Wu QF ... -  《-》

Toosendanin inhibits hepatocellular carcinoma cells by inducing mitochondria-dependent apoptosis.

Toosendanin, a triterpenoid derivative isolated from Melia toosendan Sieb. et Zucc., possesses different pharmacological effects in humans and an important value in agriculture. As indicated by previous reports, the molecular mechanisms of toosendanin's anticancer effects remain poorly clarified. In this study we used both in vivo and in vitro models to investigate the anti-cancer effects of toosendanin and their possible molecular mechanisms. In the in vitro experiment, human hepatocellular carcinoma cell lines [SMMC-7721(p53+) and Hep3B (p53-)] were coincubated with toosendanin of different concentrations (0.1~ 0.9 µM). Anti-proliferation effects were observed to be in a dose- and time-dependent manner. The IC(50) of TSN treated after 72 h for SMMC-7721 and Hep3B cells was 0.5 µM and 0.9 µM, respectively. Results from morphological analysis, annexin V staining, detection of caspases activity, and expressions of Bcl-2, Bax, and Fas indicated that the anticancer effects of toosendanin were associated with its induction of apoptosis via the mitochondria-dependent pathway in p53- and p53+ hepatocellular carcinoma cells. In the IN VIVO experiment, BALB/c mice were s.c. inoculated with mouse hepatocellular carcinoma H (22) cells. Both high-dose (0.69 mg/kg) and low-dose (0.173 mg/kg) toosendanin administrated intraperitoneally resulted in strongly suppressive effects on the tumorigenicity and apoptotic response. Results from the immunohistochemistry for Bcl-2, Bax, as well as for Fas showed that the anticancer effects of toosendanin were induced via apoptosis in a mitochondria-dependent manner, which confirmed the findings in the in vitro experiment. The findings above demonstrate that toosendanin possesses strong anticancer effects in vivo and in vitro via inducing mitochondria-dependent apoptosis in hepatocellular carcinoma cells.

He Y ，Wang J ，Liu X ，Zhang L ，Yi G ，Li C ，He X ，Wang P ，Jiang H ... -  《-》

Effects of the exopolysaccharide fraction (EPSF) from a cultivated Cordyceps sinensis on immunocytes of H22 tumor bearing mice.

Zhang W ，Li J ，Qiu S ，Chen J ，Zheng Y ... -  《FITOTERAPIA》

Ethanol extract from a Chinese herbal formula, "Zuojin Pill", inhibit the expression of inflammatory mediators in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages.

Zuojin Pill (ZJP), a traditional Chinese medicinal decoction that has been used in treating gastritis, gastric ulcer since 15th century, contains two herbs: Rhizoma Coptidis and Fructus Evodiae in the ratio of 6:1 (w/w). Alkaloids are the main active principles contributing to ZJP's efficacy, but anti-inflammatory mechanism has not been fully clarified. The objective of the study is to reveal anti-inflammatory molecular mechanism of ethanol extract from ZJP, which would form an additional proof to the traditional experience of ZJP in clinical administration. Seven alkaloids were determined from the ethanol extract of ZJP using high performance liquid chromatography (HPLC) with the gradient mobile phase. The ethanol extract from ZJP were used to evaluate the anti-inflammatory action in murine macrophage cell line RAW 264.7 treated with lipopolysaccharide (LPS). Production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) were measured by the Griess colorimetric method and enzyme-linked immunosorbent assay (ELISA), respectively. Proteome profiler array was analyzed to evaluate 40 cytokines at protein level. In addition, interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) synthesis were analyzed using ELISA to confirm the result of the Proteome profiler array. The gene expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-6, and interleukin 1β (IL-1β) were detected by quantitative real-time reverse-transcription polymerase chain reaction (real-time RT-PCR). Furthermore, the nuclear translocation of the NF-κB p50 and p65 subunits was detected with ELISA. The secretions of NO, PGE(2) and the mRNA expression of iNOS, COX-2 were significantly inhibited, moreover, the protein and mRNA expressions of IL-6, IL-1β and TNF-α were inhibited by preventing the nuclear translocation of the NF-κB p50 and p65 subunits. The proteome profiler array showed that 15 cytokines and chemokines involved in the inflammatory process were down-regulated by ZJP. These results suggest that the anti-inflammatory properties of ethanol extract from ZJP might be the results from the inhibition of iNOS, COX-2, IL-6, IL-1β, and TNF-α expression through preventing the nuclear translocation of the NF-κB p50 and p65 subunits in RAW 264.7 cells. In addition, these results provided evidence to understand the therapeutic effects of ZJP on gastritis, gastric ulcer, and other inflammatory diseases in clinic.

Wang QS ，Cui YL ，Dong TJ ，Zhang XF ，Lin KM ... -  《-》

Zanthoxylum avicennae extracts induce cell apoptosis through protein phosphatase 2A activation in HA22T human hepatocellular carcinoma cells and block tumor growth in xenografted nude mice.

Dung TD ，Chang HC ，Chen CY ，Peng WH ，Tsai CH ，Tsai FJ ，Kuo WW ，Chen LM ，Huang CY ... -  《-》