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Open AccessArticle

BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610000, China
School of Acupuncture and Massage, Beijing University of Chinese Medicine, Beijing 102488, China
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 4062;
Received: 16 July 2019 / Revised: 16 August 2019 / Accepted: 18 August 2019 / Published: 20 August 2019
(This article belongs to the Section Molecular Pharmacology)
There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistry, using a ligustrazine–betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional Prunella vulgaris plaster, BA-12 was synthesized according to our previous study, as it exhibited better antitumor activities than other derivatives on human bladder carcinoma cells (T24); it was then uploaded for target prediction. Secondly, the efficacy and biotoxicity of BA-12 on angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs), a quail chick chorioallantoic membrane, and Caenorhabditis elegans. According to the prediction results, the main mechanisms of BA-12 were metabolic pathways. Thus, multiple metabolomics approaches were applied to reveal the mechanisms of BA-12. Finally, the predictive mechanisms of BA-12 on glutathione metabolism and glycerophospholipid metabolism activation were validated using targeted metabolomics and pharmacological assays. This strategy may provide a reference for highly efficient drug discovery, with the aim of sharing TCM wisdom for unmet clinical needs. View Full-Text
Keywords: drug discovery; betulinic acid; ligustrazine; angiogenesis; metabolomics drug discovery; betulinic acid; ligustrazine; angiogenesis; metabolomics
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MDPI and ACS Style

Cui, H.; Guo, W.; Zhang, B.; Li, G.; Li, T.; Yuan, Y.; Zhang, N.; Yang, Y.; Feng, W.; Chu, F.; Wang, S.; Xu, B.; Wang, P.; Lei, H. BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation. Int. J. Mol. Sci. 2019, 20, 4062.

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