Black tea affects obesity by reducing nutrient intake and activating AMP-activated protein kinase in mice.

The effects of certain tea components on the prevention of obesity in humans have been reported recently. However, whether Yinghong NO. 9 black tea consumption has beneficial effects on obesity are not known. Here, we obtained a Yinghong NO. 9 black tea infusion (Y9 BTI) and examined the anti-obesity effects of its oral administration. ICR mice were fed a standard diet supplemented with Y9 BTI at 0.5, 1.0, or 2.0 g/kg body weight for two weeks, and the body weight were recorded. HE staining was used to evaluate the effect of Y9 BTI on mice liver. Western blot analysis was used to detect the expression levels of related proteins in the mice liver and adipose. We found that the body weights of the mice in the control group were significantly higher than those of the mice in the middle and high dose groups. The results of western blot showed that Y9 BTI up-regulated the expression of liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK) and also increased in AMPK phosphorylation (p-AMPK) and LKB1 phosphorylation (p-LKB1). Y9 BTI significantly down-regulated Fas Cell Surface Death Receptor(FAS) and activated the phosphorylation of acetyl-CoA carboxylase (ACC). Furthermore, Y9 BTI (2.0 g/kg BW) down-regulated the expression of three factors (IL-1ß, Cox-2, and iNOS). Altogether, Y9 BTI supplementation reduced the feed intake of mice and may prevent obesity by inhibiting lipid absorption. These results suggest that Y9 BTI may regulate adipogenic processes through the LKB1/AMPK pathway.

[Effects of Longzuan Tongbi Recipe on Fas/FasL Systems in Serum and Synovium of Collagen-in- duced Arthritis Rats].

Objective To observe the effect of Longzuan Tongbi Recipe (LTR) on Fas/FasL sys- tems in serum and synovium of collagen-induced arthritis (CIA) rats. Methods Ten rats were randomly selected from 60 male Wistar rats as a normal control group. CIA model was prepared by injecting type II bovine collagen and incomplete Freund's adjuvant mixture in the rest 50 rats. After modeling rats were di- vided into the model group, the methotrexate (MTX) group, high, middle, and low dose LTR groups, 10 in each group. Normal saline was administered to rats in the model group by gastrogavage. MTX solution (0.27 mg/100 g) was administered to rats in the MTX group by gastrogavage, once per week for 4 succes- sive weeks. LTR (4.32, 2.16, 1.08 g/mL) was administered to rats in the 3 LTR groups by gastrogavage, twice per day for 30 successive days. Morphological changes of synovium were observed by HE staining. Expression levels of Fas/FasL in rat serum and synovium were quantitatively detected by ELISA. Results Normal synovium cells could be seen in the normal group. But they were obviously proliferated, fat cells in the lower synovium were reduced or deformed, fibroblasts were increased in the model group, accompa- nied with infiltration of lymphocytes and monocytes. All these changes were more obviously alleviated in the MTX group, and the 3 LTR groups. Compared withI the normal control group, Fas expression level in- creased in rat serum and synovium, serum FasL expression level decreased in the model group (P <0. 05, P <0. 01). Compared with the model group, Fas expression level decreased in rat serum and synovium in the MTX group, high and middle dose LTR groups; Fas expression level in rat serum increased in the MTX group and 3 LTR groups; Fas expression level in synovium increased in the MTX group, high and middle dose LTR groups (P <0. 05, P <0. 01). Compared with the MTX group, Fas expression level in serum of the low dose LTR group, and Fas expression level in synovium of low and middle dose LTR groups was elevat- ed; Fas expression level in serum and synovium of the high dose LTR group was reduced; FasL expres- sion level in serum and synovium of low and middle dose LTR groups was reduced; FasL expression level in serum and synovium increased of the high dose LTR group (P <0. 05, P <0. 01). Conclusion LTR could control and treat rheumatoid arthritis, and its mechanism might lie in regulating. Fas/FasL systems media- ted cell apoptosis, and relieving pathological reaction of rheumatoid arthritis.

Chlorophyll a, an active anti-proliferative compound of Ludwigia octovalvis, activates the CD95 (APO-1/CD95) system and AMPK pathway in 3T3-L1 cells.

Ludwigia octovalvis is an aquatic plant widely distributed in Taiwan. It is traditionally used as a diuretic and is consumed as health drink. In this study, we evaluated the anti-proliferative activity of extracts and active constituent (chlorophyll a; CHL-a) of L. octovalvis in 3T3-L1 adipocytes; its mode of action on apoptosis was also investigated. Results showed that, among the different extracts and fractions, the ethylacetate layer (EAL) possessed the most potent anti-proliferative activity. Activity guided fractionation of the EAL obtained the bioactive constituent CHL-a (IC50: 24.10+/-0.83 nM). At concentrations 5-30 nM, CHL-a exhibited a dose-dependent accumulation of the Sub-G1 peak and caused cell cycle arrest at the G0/G1 phase. At 30 nM, it significantly reduced the cell viability, induced the appearance of DNA fragments, and enhanced the activation of caspase-3. Western blot data revealed that CHL-a decreased the level of Bcl-2, and increased the expression of CD95 (APO-1/CD95) and Bax. Furthermore, CHL-a up-regulated the AMPK and p-AMPK levels, and down-regulated the expression of PPAR-gamma. These results conclude that CHL-a possesses potent anti-proliferative activity, and its apoptotic effects on 3T3-L1 adipocytes are mediated through the activation of CD95 (APO-1/CD95) system and the AMPK signaling pathway.

Zinc inhibits ethanol-induced HepG2 cell apoptosis.

Alcohol consumption produces a variety of metabolic alterations in liver cells, associated with ethanol oxidation and with nonoxidative metabolism of ethanol, among others apoptosis of hepatocytes. As zinc is known as a potent antioxidant and an inhibitor of cell apoptosis, the aim of this paper was to investigate whether zinc supplementation could inhibit ethanol-induced HepG2 apoptosis, and whether this inhibition was connected with attenuation of oxidative stress and modulation of FasR/FasL system expression. The results indicated that zinc supplementation significantly inhibited ethanol-induced HepG2 cell apoptosis (measured by cytochrome c release from mitochondria and caspase-3 activation) by attenuation of reactive oxygen species (ROS) production, increase in the cellular level of GSH, inhibition of ethanol-induced sFasR and FasL overexpression and caspase-8 activation. These results indicate that zinc can inhibit ethanol-induced hepatocyte apoptosis by several independent mechanisms, among others by an indirect antioxidative effect and probably by inhibition of caspase-8 and caspase-9 activation.

[Immune correction in the therapy of patients with prevalent psoriasis with the help of amino acid complex]. / Immunokorrektsiia v terapii bol'nykh rasprostranennym psoriazom s pomoshch'iu aminokislotnogo kompleksa.

In patients with prevalent psoriasis a positive influence amino acid addition (with the standart therapy) on the clinical status of patients and their immune status induces. As a result of this addition use the lesion area diminished, prolongation of remission periods, reduction of the time spent in hospital.

Induction of apoptosis in human myeloid leukemic cells by 1'-acetoxychavicol acetate through a mitochondrial- and Fas-mediated dual mechanism.

PURPOSE: The purpose of this investigation was to determine the antileukemic effects of 1'-acetoxychavicol acetate (ACA) obtained from rhizomes of the commonly used ethno-medicinal plant Languas galanga (Zingiberaceae). EXPERIMENTAL DESIGN: We evaluated the effects of ACA on various myeloid leukemic cells in vitro and in vivo. We further examined the molecular mechanisms of ACA-induced apoptosis in myeloid leukemic cells. RESULTS: Low-dose ACA dramatically inhibited cellular growth of leukemic cells by inducing apoptosis. Because NB4 promyelocytic leukemic cells were most sensitive to ACA, we used NB4 cells for further analyses. Production of reactive oxygen species triggered ACA-induced apoptosis. ACA-induced apoptosis in NB4 cells was in association with the loss of mitochondrial transmembrane potential (DeltaPsim) and activation of caspase-9, suggesting that ACA-induced death signaling is mediated through a mitochondrial oxygen stress pathway. In addition, ACA activated Fas-mediated apoptosis by inducing of casapse-8 activity. Pretreatment with the thiol antioxidant N-acetyl-L-cysteine (NAC) did not inhibit caspase-8 activation, and the antagonistic anti-Fas antibody ZB4 did not block generation of reactive oxygen species, indicating that both pathways were involved independently in ACA-induced apoptosis. Furthermore, ACA had a survival advantage in vivo in a nonobese diabetic/severe combined immunodeficient mice leukemia model without any toxic effects. CONCLUSIONS: We conclude that ACA induces apoptosis in myeloid leukemic cells via independent dual pathways. In addition, ACA has potential as a novel therapeutic agent for the treatment of myeloid leukemia.

[Tumor escape mechanism involving Fas and Fas-L molecules in human colorectal tumors].

OBJECTIVES: The interaction between Fas and its ligand (Fas-L) leads to Fas-positive cell apoptosis. Our objective was to study a new mechanism of tumor escape involving these molecules, the so-called "counterattack". METHODS: We used flow cytometry to analyze Fas expression and apoptosis sensitivity in different human colorectal tumor cell lines. The presence of Fas-L mRNA was analyzed by RT-PCR. We studied apoptosis rate in peripheral blood lymphocytes and lymph node lymphocytes from patients with colorectal cancer by flow cytometric cell cycle analysis after in vitro culture with or without tumor cells. RESULTS: We found differences in Fas expression and sensitivity to Fas-induced apoptosis between different colorectal tumor cell lines. Interferon-gamma was also found to affect Fas expression and apoptosis sensitivity induced by an anti-Fas antibody. Actinomycin-D decreased Fas expression and apoptosis sensitivity in certain cell lines. Our data confirmed the tumor cell "counterattack" hypothesis by showing their capacity to induce apoptosis in lymphocytes from patients with colorectal cancer. CONCLUSION: Fas expression and apoptosis sensitivity in colorectal tumor cell lines can be modulated by actinomycin-D or interferon-gamma. These data may suggest new therapeutic options based on increased Fas expression in tumor cells induced by interferon-gamma, or on apoptosis induction in tumor cells with a local intratumoral treatment with actinomycin-D.

Role of oxidative damage and IL-1 beta-converting enzyme-like proteases in Fas-based cytotoxicity exerted by effector T cells.

The implication of oxidative damage and/or intact mitochondrial function in physiological Fas-based cytotoxicity has been tested using the cytolytic hybridoma d11S and the CD8(+) CTL clone KB5.C20, previously stimulated to express Fas ligand (FasL) on their surface, as effectors and U937 or U937-rho0 cells (depleted of mitochondrial DNA) as targets. Immobilized anti-Fas mAb, which induced death of U937 cells, inhibited the growth of U937-rho0 cells but without inducing cell death. By contrast, FasL-expressing effectors readily killed both targets, with induction of DNA fragmentation, in 20 h assays. These results demonstrate the lack of involvement of mitochondrial-derived free radicals and/or intact mitochondrial function in physiological Fas-based cytotoxicity. Supplementation of Fas-sensitive cells (Jurkat, U937, L1210Fas) with a polyunsaturated fatty acid, which induces cell death through the generation of lipid free radicals, resulted in the potentiation of Fas-based cytotoxicity. This potentiating effect, but not Fas-based cytotoxicity itself, was eliminated by the physiological antioxidant vitamin E. On the other hand, the IL-1beta-converting enzyme (ICE)-like protease tetrapeptide inhibitor Ac-YVAD-cmk partially inhibited Fas-based cytotoxicity, while the specific inhibitor of CPP32/Yama Ac-DEVD-CHO was a much more effective inhibitor of Fas-induced apoptosis. It was concluded that Fas-induced cytotoxicity was clearly dependent on ICE-like protease activation, and especially on that of CPP32 in Fas-sensitive cells, including mitochondrial DNA-depleted ones.