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The present study investigates the effects of acertannin on colitis induced by dextran sulfate sodium (DSS) and changes in the colonic levels of the cytokines interleukin (IL)-1 β , IL-6, IL-10, IL-23, tumor necrosis factor (TNF)- α , the chemokine monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF).We examine the following: inflammatory colitis was induced in mice by 2% DSS drinking water given ad libitum for 7 days. Red blood cell, platelets, and leukocyte counts and hematocrit (Ht), hemoglobin (Hb), and colonic cytokine and chemokine levels were measured. The disease activity index (DAI) was lower in DSS-treated mice orally administered acertannin (30 and 100 mg/kg) than in DSS-treated mice. Acertannin (100 mg/kg) inhibited reductions in the red blood cell count and Hb and Ht levels in DSS-treated mice. Acertannin prevented DDS-induced mucosal membrane ulceration of the colon and significantly inhibited the increased colonic levels of IL-23 and TNF- α . Our findings suggest that acertannin has potential as a treatment for inflammatory bowel disease (IBD)., Competing Interests: The authors declare that they have no conflict of interest. The authors declare that this research was conducted in the absence of any commercial or financial relationships that may be construed as a potential conflict of interest., (Thieme. All rights reserved.)

The roots of Angelica keiskei Koizumi (Umbelliferae) have traditionally been used as a health food considered to have diuretic, laxative, analeptic and lactagogue effects. Recently, it has been thought that the roots and herbs of A. keiskei have preventive effects against coronary heart disease, hypertension and cancer. It has been reported that chalcone derivatives, such as xanthoangelol and 4-hydroxyderricin, are isolated as main components from this root. Recently, we reported that the 50 % ethanol extract, the ethyl acetate-soluble fraction and the isolated xanthoangelol, inhibited tumor growth and metastasis to the lung in Lewis lung carcinoma (LLC)-bearing mice. In the present study, we examined the effects of 4-hydroxyderricin on tumor growth and metastasis to the lung or liver in subcutaneous or intrasplenic LLC-implanted C57BL/6J female mice. 4-Hydroxyderricin at a dose of 50 mg/kg x 2/day orally inhibited the tumor growth in subcutaneous LLC-implanted mice and inhibited the lung metastasis and prolonged the survival time in mice after the removal of subcutaneous tumors by surgical operation. Doxorubicin (5 mg/kg x 2/week, i. p.) inhibited the tumor growth and metastasis to the lung, but it shortened the survival time and reduced the survival rate compared to those in 4-hydroxyderricin-treated mice. 4-Hydroxyderricin inhibited DNA synthesis in LLC cells at a concentration of 100 microM, but it had no effect on the DNA synthesis in human umbilical vein endothelial cells (HUVECs) or on the adherence of LLC cells to HUVECs. 4-Hydroxyderricin inhibited Matrigel-induced formation of capillary-like tubes by HUVECs at concentrations of 10 to 100 microM. The weights of the spleen and thymus in mice with subcutaneously implanted LLC were maintained close to those of normal mice by orally administered 4-hydroxyderricin. In addition, 4-hydroxyderricin (50 mg/kg x 2/day) inhibited the reduction of the numbers of lymphocytes, CD4+, CD8+ and natural killer (NK)-T cells in the spleen of tumor-removed mice. Doxorubicin reduced the numbers of lymphocytes, CD4+, CD8+ and NK cells compared to those in LLC-removed mice. These results suggest that the antitumor and antimetastatic activities of 4-hydroxyderricin may be modulated by the immune system and the inhibition of angiogenesis.

We examined the effects of various flavonoids isolated from the roots of Scutellaria baicalensis Georgi on adhesion molecule expression induced by thrombin and thrombin receptor agonist peptide (SFLLRNPNDKYEPF, TRAP) in cultured human umbilical vein endothelial cells. Thrombin and thrombin receptor agonist peptide induced endothelial leukocyte adhesion molecule-1 (ELAM-1) expression. Intercellular adhesion molecule-1 (ICAM-1) expression was also induced by thrombin, but not by TRAP. Baicalein isolated from Scutellariae Radix inhibited ELAM-1 expression induced by thrombin and thrombin receptor agonist peptide dose-dependently, with 50% inhibitory concentrations (IC50) of 5.53 +/- 1.68 microM and 2.44 +/- 1.08 microM, respectively. Furthermore, baicalein inhibited thrombin-induced ICAM-1 expression with an IC50 of 9.67 +/- 1.28 microM. In addition, baicalein inhibited the expressions of ELAM-1 and ICAM-1 stimulated by protein kinase C (PKC) activator phorbol myristate acetate (PMA).

An EtOAc-soluble fraction from a 50% EtOH extract of the roots of Angelica keiskei inhibited phenylephrine-induced vasoconstriction in rat aortic rings, while an EtOAc-insoluble fraction had no effect at 100 micrograms/ml. Five active substances isolated from the EtOAc-soluble fraction of the roots were identified as xanthoangelol (1), 4-hydroxyderricin (2), and xanthoangelols B (3), E (4) and F (5), which inhibited phenylephrine-induced vasoconstriction at the concentrations of 10-100 micrograms/ml. It was found that xanthoangelol (1), 4-hydroxyderricin (2), and xanthoangelols E (4) and F (5) inhibited the phenylephrine-induced vasoconstriction through endothelium-dependent endothelium-derived relaxing factor (EDRF) production and/or nitric oxide (NO) production. Among the five chalcones, xanthoangelol B (3) inhibited the phenylephrine-induced vasoconstriction most strongly, and it inhibited the phenylephrine-induced vasoconstriction in the presence or absence of endothelium and in the presence or absence of NG-monomethyl-L-arginine (L-NMMA) (an NO synthetase inhibitor). Furthermore, 4-hydroxyderricin (2) and xanthoangelol B (3) at concentrations of 10-100 micrograms/ml concentration-dependently inhibited the elevation of intracellular free calcium [Ca2+]i induced by phenylephrine. These results demonstrate that compounds 1, 2, 4 and 5 inhibit phenylephrine-induced vasoconstriction through endothelium-dependent production of EDRF/NO and/or through the reduction of the [Ca2+]i elevation induced by phenylephrine. On the other hand, the inhibitory mechanism of compound 3 on phenylephrine-induced vasoconstriction might involve the direct inhibition of smooth muscle functions through the reduction of [Ca2+]i elevation without affecting EDRF/NO production.

A new naphtoquinone and 9 known phenolic components were isolated from a Japanese drug the roots of POLYGONUM CUSPIDATUM. The new component was proved to be 2-methoxy-6-acetyl-7-methyljuglone.