[Application of mixture analysis methods in association between metals mixture exposure and DNA oxidative damage].

Objectives: To study the association between metals mixture exposure and DNA oxidative damage using mixture analysis methods, and to explore the most significant exposure factors that cause DNA oxidative damage. Methods: Workers from steel enterprises were recruited in Shandong Province. Urinary metals were measured by using the inductively coupled plasma mass spectrometry method. The level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined by using the ultra-high performance liquid chromatography-mass spectrometry method. Bayesian kernel machine regression (BKMR), elastic net regression and quantile g-computation regression were used to analyze the association between urinary metals and urinary 8-OHdG. Results: A total of 768 subjects aged (36.15±7.40) years old were included in the study. BKMR, elastic net regression and quantile g-computation all revealed an overall positive association between the mixture concentration and increased urinary 8-OHdG. The quantile g-computation results showed that with a 25% increase in metal mixtures, the urinary 8-OHdG level increased by 77.60%. The elastic net regression showed that with a 25% increase in exposure risk score, the urinary 8-OHdG level increased by 26%. The BKMR summarized the contribution of individual exposures to the response, and selenium, zinc, and nickel were significant contributors to the urinary 8-OHdG elevation. Conclusion: Exposure to mixed metals causes elevated levels of DNA oxidative damage, and selenium, zinc, and nickel are significant exposure factors.

Simultaneous HPLC determination of four active compounds in fengshiding capsules, a chinese medicine.

A high performance liquid chromatography method was established for simultaneously determining four bioactive components, salicin, liquiritin, paeonolum, and imperatorin in Fengshiding capsule, a widely used traditional Chinese medicine for treating rheumatic disease. The chromatographic separation was performed on a Shimadzu Shim-pack Stable Bond C18 column using gradient elution with methanol and water. The analytical method was validated through precision, repeatability and stability, and the relative standard deviation values were less than 3%, respectively. The recoveries of the four investigated compounds ranged from 95.80 to 101.21% with relative standard deviation values less than 3.2%. Then this proposed method was successfully applied to determine six batches of Fengshiding commercial products of capsule dosage form from two pharmaceutical factories. This study might provide a basis for quality control for this traditional Chinese medicine preparation.

Anti-cancer activities of tea epigallocatechin-3-gallate in breast cancer patients under radiotherapy.

The purpose of this study was to test the hypothesis that administration of epigallocatechin-3-gallate (EGCG), a polyphenol present in abundance in widely consumed tea, inhibits cell proliferation, invasion, and angiogenesis in breast cancer patients. EGCG in 400 mg capsules was orally administered three times daily to breast cancer patients undergoing treatment with radiotherapy. Parameters related to cell proliferation, invasion, and angiogenesis were analyzed while blood samples were collected at different time points to determine efficacy of the EGCG treatment. Compared to patients who received radiotherapy alone, those given radiotherapy plus EGCG for an extended time period (two to eight weeks) showed significantly lower serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and reduced activation of metalloproteinase-9 and metalloproteinase-2 (MMP9/MMP2). Addition of sera obtained from patients treated with combination of radiotherapy and EGCG feeding for 2-8 weeks to in vitro cultures of highly-metastatic human MDA-MB-231 breast cancer cells resulted in the following significant changes: (1) suppression of cell proliferation and invasion; (2) arrest of cell cycles at the G0/G1 phase; (3) reduction of activation of MMP9/MMP2, expressions of Bcl-2/Bax, c-Met receptor, NF-κB, and the phosphorylation of Akt. MDA-MB-231 cells exposed to 5-10 µM EGCG also showed significant augmentation of the apoptosis inducing effects of γ-radiation, concomitant with reduced NF-κB protein level and AKT phosphorylation. These results provide hitherto unreported evidence that EGCG potentiated efficacy of radiotherapy in breast cancer patients, and raise the possibility that this tea polyphenol has potential to be a therapeutic adjuvant against human metastatic breast cancer.

Anti-thrombosis effect of paeoniflorin: evaluated in a photochemical reaction thrombosis model in vivo.

In a photochemical reaction microvessel thrombosis model, the anti-thrombotic effect of PT was evaluated and the results showed that PF could significantly prolong thromobosis time. The anti-thrombotic effect of PF may relate to the inhibition of arachidonic acid metabolism, the increase of t-PA activity, and the protective effect against free radical.

Immunosuppressive sesquiterpene alkaloids from Tripterygium wilfordii.

Nine new sesquiterpene pyridine alkaloids [wilfornines A (1), B (2), C (3), D (4), E (5), F (8), and G (9); wilfordinines I (6) and J (7)] and six known compounds (10-15) were isolated from a clinically used extract (T(II)) of Tripterygium wilfordii. The structures of 1-9 were elucidated by spectroscopic and chemical methods. The inhibitory effects on cytokine production of 1-3 and several related compounds were evaluated. Compounds 10 and 14 showed significant inhibitory effects on cytokine production.

Sesquiterpene polyol esters from Tripterygium wilfordii.

The extract (T(II)) of Tripterygium wilfordii Hook f. afforded four sesquiterpene esters: 1beta,2beta,5alpha,8beta,11-pentaacetoxy-4alpha-hydroxy-3alpha(2'-methylbutanoyl)-15-nicotinoyl-7-oxo-dihydroagarofuran; 1beta,5alpha,11-triacetoxy-7beta-benzoyl-4alpha-hydroxy-8beta-nicotinoyl-dihydroagarofuran; 1beta,2beta,5alpha,11-tetraacetoxy-8alpha-benzoyl-4alpha-hydroxy-7beta-nicotinoyl-dihydroagarofuran; 5alpha-benzoyl-4alpha-hydroxy-1beta,8alpha-dinicotinoyl-dihydro- agarofuran as well as one other known sesquiterpene ester. Their structures were established on the basis of spectroscopic studies.

Triterpenoids from Tripterygium wilfordii.

The extract (T(II)) of Tripterygium wilfordii Hook f. afforded four triterpenoids: wilforic acid D (3beta,24-epoxy-2alpha-hydroxy-24R*-ethoxy-29-friedelanoic acid); (E) 3beta,24-epoxy-2-oxo-3alpha-hydroxy-29-friedelanoic acid; (F) 2beta-hydroxy-3-oxo-friedelan-29-oic acid; 29-hydroxy-3-oxo-olean-12-en-28-oic acid and 17 known triterpenoids. Their structures were established on the basis of spectroscopic studies. In a bioactivity analysis, only the known dulcioic acid compound showed a significant inhibitory effect on cytokine production.

Sesquiterpene alkaloids from Tripterygium hypoglaucum and Tripterygium wilfordii: a new class of potent anti-HIV agents.

Five new sesquiterpene pyridine alkaloids [triptonines A (1) and B (2), and wilfordinines A (3), B (4), and C (5)] and two known compounds (peritassine A and hypoglaunine C) were isolated from Tripterygium hypoglaucum and a clinically used extract of Tripterygium wilfordii. The structures of 1-5 were elucidated by spectroscopic methods. The anti-HIV activity of 1, 2, and several related compounds was evaluated. Triptonine B (2) demonstrated potent anti-HIV activity with an EC(50) value of <0.10 microg/mL and an in vitro therapeutic index value of >1000.

Coumarins and bicoumarin from Ferula sumbul: anti-HIV activity and inhibition of cytokine release.

The methanol extract of the dried roots of Ferula sumbul afforded two furanocoumarin esters, fesumtuorin A, B, one bicoumarin, fesumtuorin C, five spirobicoumarins, fesumtuorin D, E, F, G and H, along with nineteen known coumarins. Their structures were established on the basis of spectroscopic studies. Some of the isolated compounds showed anti-HIV activity and very weak inhibition of cytokine release.

Terpenoids from Tripterigyum hypoglaucum.

Six terpenoids have been isolated from the root bark of Tripterygium hypoglaucum, along with 14 known compounds. The structures of the terpenoids were elucidated as 3,11,14-oxo-abieta-8,12-diene, 3beta-hydroxy-12,14-dimethoxyabieta-8,11,13-triene, 3beta-hydroxy-11alpha-ethoxyurs-12-ene, 3beta-hydroxy-11alpha-methoxyurs-12-ene, 3beta-hydroxy-11alpha-methoxyolean-12-ene-28-oic acid, and 1beta-benzoyl-8alpha-cinnamoyl-4alpha,5alpha- dihydroxydihydroagarofuran.

Immunosuppressive diterpenoids from Tripterygium wilfordii.

A clinically used extract of Tripterygium wilfordii afforded three new diterpenoids-3beta,19-dihydroxyabieta-8,11,13-triene (triptobenzene L) (1); 12,19-dihydroxy-3-oxoabieta-8,11,13-triene (triptobenzene M) (2); and 19-hydroxy-3,7-dioxo-abieta-8,11, 13-triene (triptobenzene N) (3)-along with 14 known diterpenoids. The structures of 1-3 were established on the basis of spectroscopic studies. Of the known compounds, the stereochemistry at C-4 of triptonediol (4) was reassigned. Tripterifordin (8) and 13-epi-manoyl oxide-18-oic acid (9) showed significant inhibitory effects on cytokine production.

[Effect of age and ginsenoside Rg1 on nitric oxide content and nitric oxide synthase activity of cerebral cortex in rats].

Nitric oxide(NO) content and nitric oxide synthase(NOS) activity were measured in cerebral cortex isolated from Wistar rats of three age groups(young: 3 months; adult: 9 months; and old: 27 months). No significant differences in NO content and NOS activity between young and adult rats were found(P > 0.05). The NO content and NOS activity in old rats were shown to be significantly higher than those of young and adult rats(P < 0.01). When treated with Rg1(10, 20, 40 mg.kg-1), the NO content and NOS activity in old rats decreased. The inhibitory effect of Rg1 on NOS was found to be dose-dependent in the range of 10-40 mg.kg-1. The optimal reduction in NO content and NOS activity induced by Rg1 occurred at 40 mg.kg-1 for old rats(P < 0.01). In view of the close relationship of NO content and NOS activity with aging, the inhibitory effect of Rg1 on NOS activity, as shown by our results, might provide an explanation for its antiaging function.

Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase.

The Eph family of receptor protein tyrosine kinases (RPTKs) is the largest family of RPTKs. The signal transduction pathways initiated by this family have only recently begun to be explored. Using a yeast two-hybrid screen to identify molecules that interact with the cytoplasmic domain of Eck, it was previously shown that activated Eck RPTK bound to and stimulated phosphatidylinositol 3-kinase (Pandey, A., Lazar, D.F., Saltiel, A. R., and Dixit, V.M. (1994) J. Biol. Chem. 269, 30154-30157). Also isolated from this same screen was a novel protein containing SH3 and SH2 adapter modules that had striking homology to those found in the Src family of non-receptor tyrosine kinases. However, unlike other Src family members, it lacked a catalytic tyrosine kinase domain. Hence, this protein was designated SLAP for Src-like adapter protein. Using glutathione S-transferase fusion Proteins, it was demonstrated that SLAP bound to activated Eck receptor tyrosine kinase. Therefore, SLAP is a novel candidate downstream signaling intermediate and the first member of the Src family that resembles an adapter molecule.