Indirubin shows anti-angiogenic activity in an in vivo zebrafish model and an in vitro HUVEC model
Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China. Journal of ethnopharmacology
(Impact Factor: 3).
09/2010; 131(2):242-7. DOI: 10.1016/j.jep.2010.05.016
Indirubin is an active ingredient of the traditional Chinese medicine, Dang Gui Long Hui Wan, commonly used for the treatment of chronic myelocytic leukemia (CML) and other inflammatory conditions. These anti-leukemic and anti-inflammatory activities may be mediated by anti-angiogenic action. To investigate the anti-angiogenic activity of indirubin, we tested its inhibitory effect on blood vessel formation in zebrafish embryos and on endothelial cell proliferation in culture.
The anti-angiogenic activity of indirubin was tested using transgenic zebrafish embryos with fluorescent vasculature and human umbilical vein endothelial cells (HUVECs). Apoptosis was analyzed with a terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay.
Indirubin dose-dependently inhibited intersegmental vessel formation in zebrafish embryos. It also inhibited HUVEC proliferation by the induction of cellular apoptosis and cell-cycle arrest at the G0/G1 phase.
The anti-angiogenic activity of indirubin may partly contribute to its anti-leukemic and anti-psoriatic properties and may be valuable for the treatment of diseases with excessive angiogenesis. The zebrafish model of angiogenesis was further validated in this study.
Available from: Ming-Zhong Sun
- "rAdinbitor administration also suppressed or even eliminated the symptoms of asthma, dyspnea and emaciation of H22-bearing mice. Disintegrins inhibit either spontaneous or tumor-associated angiogenesis specifically on newly formed vessels    . rAdinbitor exhibits tumor suppression via angiogenesis inhibiting. "
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ABSTRACT: Adinbitor is a disintegrin previously obtained from Agkistrodon halys brevicaudus stejneger by our group. Here, we investigated the in vitro and in vivo anti-tumor activities of recombinant Adinbitor (rAdinbitor). rAdinbitor stimulation can inhibit the in vitro proliferation, migration and invasion capacities of murine hepatocarcinoma H22 and Hca-F cells. The administrations of rAdinbitor either by gavage or intraperitoneal injection suppress the tumor malignancy and prolong the survival rate and time of H22-transplanted mice. The number and size of formed blood vessels decreased dramatically in tumorous tissues in that the expression levels of vascular endothelial growth factor (VEGF) and cluster of differentiation 34 (CD34) were significantly decreased in responding to rAdinbitor treatment. The protein levels of IL-18 and IgG increased significantly in the serum of H22-transplanted tumor mice with rAdinbitor treatment. rAdinbitor shows in vitro and in vivo anti-tumor effects as an angiogenesis inhibitor and immunocompetence enhancer.
Copyright © 2015. Published by Elsevier B.V.
Available from: Jin-Wen Xu
- "The organic pesticide rotenone has been found to cause DA neurotoxicity. Both the polysaccharides from Cordyceps militaris and the extract of Acanthopanax senticosus have shown the protective effect against rotenone-induced oxidative damage in Drosophila melanogaster [58, 59]. "
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ABSTRACT: Traditional Chinese medicine (TCM) is an ancient medical system with a unique cultural background. Nowadays, more and more Western countries due to its therapeutic efficacy are accepting it. However, safety and clear pharmacological action mechanisms of TCM are still uncertain. Due to the potential application of TCM in healthcare, it is necessary to construct a scientific evaluation system with TCM characteristics and benchmark the difference from the standard of Western medicine. Model organisms have played an important role in the understanding of basic biological processes. It is easier to be studied in certain research aspects and to obtain the information of other species. Despite the controversy over suitable syndrome animal model under TCM theoretical guide, it is unquestionable that many model organisms should be used in the studies of TCM modernization, which will bring modern scientific standards into mysterious ancient Chinese medicine. In this review, we aim to summarize the utilization of model organisms in the construction of TCM syndrome model and highlight the relevance of modern medicine with TCM syndrome animal model. It will serve as the foundation for further research of model organisms and for its application in TCM syndrome model.
Available from: Kelvin Chan
- "Sprout formation was seen as the main characteristic in proangiogenesis [17, 120, 121]. Recently, we demonstrated the feasibility of drug screening in a zebrafish model and found the antiangiogenesis effect of a resveratrol derivative , indirubin , nobiletin , and sinensetin  as well as proangiogenesis effects of Angelica sinensis extract [123, 124], Panax notoginseng extract , and Radix Astragali extract . "
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ABSTRACT: The zebrafish (
) has recently become a common model in the fields of genetics, environmental science, toxicology, and especially drug screening. Zebrafish has emerged as a biomedically relevant model for
high content drug screening and the simultaneous determination of multiple efficacy parameters, including behaviour, selectivity, and toxicity in the content of the whole organism. A zebrafish behavioural assay has been demonstrated as a novel, rapid, and high-throughput approach to the discovery of neuroactive, psychoactive, and memory-modulating compounds. Recent studies found a functional similarity of drug metabolism systems in zebrafish and mammals, providing a clue with why some compounds are active in zebrafish
, as well as providing grounds for the rationales supporting the use of a zebrafish screen to identify prodrugs. Here, we discuss the advantages of the zebrafish model for evaluating drug metabolism and the mode of pharmacological action with the emerging omics approaches. Why this model is suitable for identifying lead compounds from natural products for therapy of disorders with multifactorial etiopathogenesis and imbalance of angiogenesis, such as Parkinson's disease, epilepsy, cardiotoxicity, cerebral hemorrhage, dyslipidemia, and hyperlipidemia, is addressed.
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