Ruscogenin suppresses mouse neutrophil activation: Involvement of protein kinase A pathway.

Ruscogenin, a natural steroidal sapogenin, presents in both food and medicinal plants. It has been found to exert significant anti-inflammatory activities. Considering that activation of neutrophil is a key feature of inflammatory diseases, this study was performed to investigate the inhibitory effect of ruscogenin and its underlying mechanisms responsible for neutrophil activation. Ruscogenin displayed potent antioxidative effects against Formyl-Met-Leu-Phe (FMLP)-induced extra- and intracellular superoxide generation in mouse bone marrow neutrophils, with IC50 values of 1.07±0.32 µM and 1.77±0.46 µM, respectively. Phorbol myristate acetate (PMA)-elicited extra- and intracellular superoxide generation were also suppressed by ruscogenin, with IC50 values of 1.56±0.46 µM and 1.29±0.49 µM, respectively. However, ruscogenin showed weak inhibition in NaF-induced response. Inhibition of superoxide generation was mediated neither by a superoxide-scavenging ability nor by a cytotoxic effect. Furthermore, ruscogenin inhibited the membrane translocation of p47phox and p67phox. It reduced FMLP-induced phosphorylation of cytosolic phospholipase A2 (cPLA2) and p21-activated kinase (PAK). The cellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) expression were increased by ruscogenin. Moreover, ruscogenin inhibited phosphorylation of protein kinase B (Akt), p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK). In addition, the inhibitory effects of ruscogenin on superoxide production and the phosphorylation of Akt, p38MAPK, and ERK1/2 were reversed by PKA inhibitor (H89), suggesting a PKA-dependent mechanism. In summary, our data suggest that ruscogenin inhibits activation of neutrophil through cPLA2, PAK, Akt, MAPKs, cAMP, and PKA signaling pathways. Increased PKA activity is associated with suppression of the phosphorylation of Akt, p38MAPK, and ERK1/2 pathways.

Opposite effects of genistein on the regulation of insulin-mediated glucose homeostasis in adipose tissue.

BACKGROUND AND PURPOSE: Genistein is an isoflavone phytoestrogen found in a number of plants such as soybeans and there is accumulating evidence that it has beneficial effects on the regulation of glucose homeostasis. In this study we evaluated the effect of genistein on glucose homeostasis and its underlying mechanisms in normal and insulin-resistant conditions. EXPERIMENTAL APPROACH: To induce insulin resistance, mice or differentiated 3T3-L1 adipocytes were treated with macrophage-derived conditioned medium. A glucose tolerance test was used to investigate the effect of genistein. Insulin signalling activation, glucose transporter-4 (GLUT4) translocation and AMP-activated PK (AMPK) activation were detected by Western blot analysis or elisa. KEY RESULTS: Genistein impaired glucose tolerance and attenuated insulin sensitivity in normal mice by inhibiting the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1) at tyrosine residues, leading to inhibition of insulin-mediated GLUT4 translocation in adipocytes. Mac-CM, an inflammatory stimulus induced glucose intolerance accompanied by impaired insulin sensitivity; genistein reversed these changes by restoring the disturbed IRS1 function, leading to an improvement in GLUT4 translocation. In addition, genistein increased AMPK activity under both normal and inflammatory conditions; this was shown to contribute to the anti-inflammatory effect of genistein, which leads to an improvement in insulin signalling and the amelioration of insulin resistance. CONCLUSION AND IMPLICATIONS: Genistein showed opposite effects on insulin sensitivity under normal and inflammatory conditions in adipose tissue and this action was derived from its negative or positive regulation of IRS1 function. Its up-regulation of AMPK activity contributes to the inhibition of inflammation implicated in insulin resistance.

[Non-anthraquinone constituents from Rheum sublanceolatum C. Y. Cheng et Kao].

OBJECTIVE: Study on the non-anthraquinone constituents from rhizoma and radix of Rheum sublanceolatum. METHOD: The constituents were isolated through column chromatography and identified on the basis of their physiochemical and spectral data. RESULT: Six non-anthraquinone constituents were isolated and identified as n-octacosanic acid, sitosterol, daucosterol, 2-methyl-5-carboxymethyl-7-hydroxychromone, piceatannol and 6-hydroxymusizin-8-O-beta-D-glucopyranoside. CONCLUSION: All these compounds were firstly isolated from R. sublanceolatum.

Anti-allergic effect of an aqueous extract of wu-hu-tang.

Wu-Hu-Tang (WHT), a Chinese formulation which consists of seven crude drugs, has been used for the treatment of asthma for hundreds of years. In this paper, an investigation on the anti-allergic activity of an aqueous extract of WHT was undertaken to find the pharmacological basis for the ethnomedical use of the formulation. WHT produced a significant inhibition on the homologous passive cutaneous anaphylaxis (PCA) in rats and the heterologous PCA in mice, decreased the degranulation of mast cells of calvarial periosteum in rats, inhibited the release of anaphylactic mediators from sensitized lung tissues of guinea pigs and the contraction of isolated guinea pigs ileum induced by histamine. These results indicated that the therapeutic activity of WHT for asthma may be related to its inhibitory effects on immediate hypersensitivity.