Protective role of wogonin against lipopolysaccharide-induced angiogenesis via VEGFR-2, not VEGFR-1
Lin C-M et al. International Immunopharmacology. Volume 6, Issue 11, November 2006, Pages 1690-1698. doi:10.1016/j.intimp.2006.07.003 Wogonin, one of flavonoid derived from particular plants, enriches the property of anti-inflammation. Inflammation-stimulated angiogenesis plays an important role in many pathological diseases, such as rheumatoid arthritis, atherosclerosis, and cancer. The aim of this study was to investigate the suppressive effect of wogonin on lipopolysaccharide (LPS)-induced angiogenesis in human umbilical endothelial cell (HUVEC) cultures. By cell differentiation assays, migration and tube formation activity under LPS treatment were evaluated. Besides, IL-6 neutralizing antibody was added to test the inhibitory effect in the phenotypic alteration. Western blot analysis, ELISA cytokine assay, and quantitative real time-PCR were performed for VEGF, IL-6, VEGF receptors, and IL-6 receptor gene expressions on HUVEC with wogonin treatment. Furthermore, in vivo chorioallantoic membrane (CAM) assay was applied to evaluate the percentage of new vessels formation. The results revealed that wogonin (10? 8–10? 5 M) inhibited LPS-induced angiogenesis in a concentration-dependent manner. The mRNA and protein expressions of VEGF, VEGFR-2, IL-6, and sIL-6R? were attenuated (P < 0.05), but not VEGFR-1. In the LPS-induced CAM model, our data suggested that wogonin (10? 8–10? 5 M) significantly decreased new vessel formation and vascular network (P < 0.05). We conclude that wogonin suppresses both in vitro and in vivo LPS-induced angiogenesis, through VEGFR-2, but not VEGFR-1
New therapeutic aspects of flavones: The anticancer properties of Scutellariae and its main active constituents Wogonin, Baicalein and Baicalin
Cancer Treatment Reviews. Volume 35, Issue 1, February 2009, Pages 57-68 doi:10.1016/j.ctrv.2008.09.005
Traditional Chinese medicines have been recently recognised as a new source of anticancer drugs and new chemotherapy adjuvant to enhance the efficacy of chemotherapy and to ameliorate the side effects of cancer chemotherapies however their healing mechanisms are still largely unknown. Scutellaria baicalensis is one of the most popular and multi-purpose herb used in China traditionally for treatment of inflammation, hypertension, cardiovascular diseases, and bacterial and viral infections. Accumulating evidence demonstrate that Scutellariae also possesses potent anticancer activities. The bioactive components of Scutellariae have been confirmed to be flavones. The major constituents of Scutellariae baicalensis are Wogonin, Baicalein and Baicalin. These phytochemicals are not only cytostatic but also cytotoxic to various human tumour cell lines in vitro and inhibit tumour growth in vivo. Most importantly, they show almost no or minor toxicity to normal epithelial and normal peripheral blood and myeloid cells. The antitumor functions of these flavones are largely due to their abilities to scavenge oxidative radicals, to attenuate NF-?B activity, to inhibit several genes important for regulation of the cell cycle, to suppress COX-2 gene expression and to prevent viral infections. The tumour-selectivity of Wogonin has recently been demonstrated to be due to its ability to differentially modulate the oxidation–reduction status of malignant vs. normal lymphocytic cells and to preferentially induce phospholipase C?1, a key enzyme involved in Ca2+ signalling, through H2O2 signalling in malignant lymphocytes. This review is aimed to summarise the research results obtained since the last 20 years and to highlight the recently discovered molecular mechanisms.
Wogonin suppresses tumour growth in vivo and VEGF-induced angiogenesis through inhibiting tyrosine phosphorylation of VEGFR2
Lu et al. Life Sciences. Volume 82, Issues 17-18, 23 April 2008, Pages 956-963 doi:10.1016/j.lfs.2008.02.013
Previous studies revealed that wogonin, a naturally occurring monoflavonoid extracted from Scutellariae radix, possessed anticancer activity both in vitro and in vivo. However, the molecular mechanism of its potent anticancer activity remains poorly understood and warrants further investigations. In this study, we found for the first time that wogonin inhibited the growth and tumour angiogenesis of human gastric carcinoma in nude mice. We explored the inhibitory effect of wogonin on angiogenesis stimulated by vascular endothelial growth factor (VEGF) in vitro. Wogonin suppressed the VEGF-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs). It also restrained VEGF-induced tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). This inhibition of receptor phosphorylation was correlated with a significant decrease in VEGF-triggered phosphorylated forms of ERK, AKT and p38. Taken together, these findings strongly suggest that wogonin might be a promising antitumour drug.
Effects of Flavonoids on Acute and Chronic Inflammatory Responses Caused by Tumor Necrosis Factor α
Yoshio K et al. Current Pharmaceutical Design, Volume 12, Number 32, November 2006 , pp. 4271-4279(9)
Flavonoids have beneficial activities which modulate oxidative stress, allergy, tumour growth and viral infection, and which stimulate apoptosis of tumour cells. In addition to these activities, dietary flavonoids are able to regulate acute and chronic inflammatory responses. Here we describe new aspects of regulatory mechanisms by which flavonoids suppress production of tumor necrosis factor-? (TNF-?) by macrophages, microglial cells and mast cells stimulated with lipopolysaccharide (LPS) and others via toll-like receptors (TLRs), and TNF-?-mediated acute and chronic inflammatory responses. Treatment with flavonoids such as luteolin, apigenin, quercetin, genistein, (-)-epigallocatechin gallate, and anthocyanidin resulted in significant down-regulation of LPS-elicited TNF-? and nitric oxide (NO) production and diminished lethal shock. In chronic diseases, pathogenesis of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis which is triggered by TNF-?, was improved by the oral administration of flavonoids after the onset of CIA. Here, we discuss that inhibitory effects of flavonoids on acute and chronic inflammation are due to regulation of signalling pathways, including the nuclear factor ?B (NF-?B) activation and mitogen-activated protein (MAP) kinase family phosphorylation. Fc?RI expression by NF-?B activation was also reduced by flavonoids; while accumulation of lipid rafts, which is the critical step for signalling, was blocked by flavonoids. The intake of dietary flavonoids reduces acute and chronic inflammation due to blocking receptor accumulation and signalling cascades, and would assist individuals at high risk from life-style related diseases.
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