Three new hasubanan-type alkaloids from the Stephania longa.

Three new hasubanan-type alkaloids, stephalonine Q (1), stephalonine R (2) and stephalonine S (3), together with four known alkaloids, isolonganone (4), eletefine (5), aurantiamide (6), N-cinnamoyltyramine (7), were isolated from the whole plant of Stephania longa. Their structures were identified by NMR, HR-ESI-MS, CD methods and x-ray crystallography, as well as by comparison with the literature data. All isolated compounds were evaluated for their antimicrobial activities against five bacteria in vitro. Compound 5 displayed inhibitory activity against only S. aureus, with an MIC value of 50 µg/mL.

Hasubanan alkaloids with anti-inflammatory activity from Stephania longa.

Two new hasubanan alkaloids, stephalonester A (1) and stephalonester B (2), together with four known compounds, stephalonine E (3), longanone (4), cephatonine (5), and prostephabyssine (6) were isolated from the whole plant of Stephania longa. Their structures were determined by HR-ESI-MS, 1 D and 2 D NMR, ECD calculations, as well as by comparison with literature values. All compounds were evaluated for their anti-inflammatory activity in vitro. Compounds 4, 5, and 6 exhibited significantly inhibitory effects on TNF-α and IL-6 production with IC50 values range from 6.54 to 30.44 µM.

Integrated analysis of 10 lymphoma datasets identifies E2F8 as a key regulator in Burkitt's lymphoma and mantle cell lymphoma.

Burkitt's lymphoma (BURK), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are three main types of B-cell lymphomas. This study aimed to compare the differences of affected biological functions and pathways, as well as to explore the possible regulatory mechanisms and the potential therapeutic targets in BURK, DLBCL and MCL. We performed an integrated analysis of 10 lymphoma datasets including 352 BURK patients, 880 DLBCL patients, 216 MCL patients, and 33 controls. Our results showed that signaling pathways, amino acid metabolism and several lipid metabolism pathways varies considerably among these three types of lymphoma. Furthermore, we identified several key transcription factors (TFs) and their target genes that may promote these diseases by influencing multiple carcinogenic pathways. Among these TFs, we reported first that E2F8 displayed the most significant effects in BURK and MCL. Our results demonstrate that over-expression of E2F8 activates target genes that may promote cell cycle, mitosis, immune and other cancer related functions in BURK and MCL. Therefore, we suggest that E2F8 could be used as a biomarker and potential therapeutic target for BURK and MCL. These findings would be helpful in the study of pathogenesis, and drug discovery and also in the prognosis of B cell lymphomas.

Screening bioactive components of Glycyrrhiza uralensis Fisch. with isolated perfused lung extraction and HPLC-ESI-MSn analysis.

The isolated perfused rat lung (IPL), coupled with high performance liquid chromatography\tandem mass spectrometry analysis (HPLC-ESI-MSn), has been developed as a tool for screening bioactive components in Glycyrrhiza uralensis Fisch. (GU). First, IPL was perfused with the water extract of GU (EGU), the bioactive components in the EGU would selectively combine to the receptors or channels of lung. By changing the pH of perfused solution, the combined components were eluated and then detected by HPLC-ESI-MSn. Four compounds were detected in the desorption eluate of IPL, among these compounds, liquiritin (1), ononin (2) and glycyrrhizic acid (4) were identified by comparing with the chromatography of the standards, while licorice-saponin G2 (3) were determined by analysis of the structure clearage characterization of mass spectrometry. Then, due to the lack of compound 3 sample, compounds 1, 2 and 4 with respective concentrations of 50 µM, 5 µM, 500 nM, 50 nM and 5 nM were applied to evaluate the protective effect of pulmonary epithelial cells (PEC, A549 cell) injury induced by lipopolysaccharide (LPS) for anti-inflammatory activity assessment. The results showed that except the 5 nM group of compound 1, 5 nM and 50 nM groups of compound 2, all other groups could remarkably inhibit the PEC injury (vs LPS group, 2-500 nM groups: p < 0.05; other groups: p < 0.01), all compound showed the dose-dependent effect. In conclusion, IPL coupled with HPLC-ESI-MSn was successfully used to screen the anti-inflammatory components of GU for the first time. The application of IPL coupled with HPLC-ESI-MSn for screening bioactive components of TCMs is rapid, convenient and reliable, and the isolated perfused technology could be extended to isolated heart, liver, kidney, and so on.

[Radioprotective effect of aloe polysaccharides on three non-tumor cell lines].

BACKGROUND & OBJECTIVE: Our previous study showed that aloe polysaccharides (AP) could evidently decrease the mortality of irradiated mice mainly through increasing the amount of hemocytes and ameliorating immune function of mice. Whether AP can protect the cells in vitro from irradiation damage is unknown. This study was to explore radioprotective effect of AP on 3 non-tumor cell lines, and its effect on cell cycle. METHODS: MTT assay was used to detect cytotoxicities of AP to normal human liver cell line Chang Liver (C. Liver), normal human embryo kidney cell line 293, and normal human umbilicus vein endothelial cell line ECV304. The 3 cell lines were treated with AP before or after irradiation. After 7-10 days normal culture, survival rate of cells was calculated by clone formation assay. Cell cycle was analyzed by flow cytometry (FCM) at different time points after irradiation. RESULTS: 293 cells were treated with AP at different time points before and after x-ray irradiation. Survival rate of 293 cells treated with AP 30 min before x-ray irradiation was the highest (64.2%) among all groups. Evident dosage-effect relationship of AP appeared in concentration range of 12.5-50 microg/ml. After treatment of 50 microg/ml of AP, survival rates of 293, ECV304, and C. Liver cells increased from 41.5%, 46.5%, and 40.9% to 49.4%, 72.1%, and 89.1%, respectively. Irradiation caused a distinct G(2)/M block and decreased G(0)/G(1) phase population in 293 and C. Liver cells. In C. Liver cells, pretreatment of 50 mug/ml of AP increased G(0)/G(1) phase population from 31.8% to 43.8%, decreased G(2)/M phase population from 38.5% to 13.8% 6 h after irradiation; and decreased G(2)/M phase population from 22.9% to 8.7% 24 h after irradiation. In 293 cells, the same pretreatment increased G(0)/G(1) phase population from 30.1% to 45.9% 6 h after irradiation, and from 40.4% to 45.2% 24 h after irradiation accompanied by decrease of G(2)/M population from 59.6% to 54.1%. CONCLUSIONS: AP has radioprotective effect on non-tumor cells. This effect might relate to alleviating of cell cycle turbulence.

Aloe polysaccharides mediated radioprotective effect through the inhibition of apoptosis.

Polysaccharides from aloe are always considered an effective radioprotector on irradiation-induced skin damage. The aim of this study was to determine if aloe polysaccharides (AP) have radioprotective effects on normal human cells in vitro and mouse survival in vivo and to explore the mechanism. Pretreatment with 50 microg/ml AP could improve the surviving fraction at 2 Gy (SF2) of three normal cell lines 293, ECV304, and C. liver from 41.5%, 46.5%, and 40.9% to 49.4%, 72.1%, and 89.1%, respectively. AP could also reduce the apoptotic rate of C. liver cells from 9.5% and 43.0% to 2.2% and 10.9% 48 h and 72 h after 2 Gy irradiation, respectively. Western blot analysis showed that pretreatment with AP could block the upregulation of pro-apoptotic p53, Bax, and Bad and the downregulation of Bcl-2 by irradiation. AP could lower thymocyte apoptosis of mice in vivo after 6 Gy irradiation and abrogate the cell cycle perturbation. Fifty mg/kg of AP treatment for 30 min before 7.5 Gy irradiation provided the best radioprotective effect and improved the 30-day survival rate of mice to 86.0%, from 10.0%. AP exerted radioprotective effects in vitro and in vivo through an inhibition of apoptosis.