J Cancer 2021; 12(1):124-133. doi:10.7150/jca.52971

Research Paper

Screening Study on the Anti-Angiogenic Effects of Traditional Chinese Medicine - Part II: Wild Chrysanthemum

Xiang Tu1*, He Bin Wang2*, Qun Huang3*, Yi Cai4, Yuan Ping Deng5, Zhe Yong6, Quan Hu7, Jian Feng8, James B. Jordan1, Sen Zhong1✉

1. Cancer Research Institute, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
2. Department of Hepatology, Affiliated Hospital of Panzhihua University, Panzhihua 617000, Sichuan Province, China
3. Department of Pathology, 363 Hospital of Aviation Industry Corporation of China, Ltd., Chengdu 610041, Sichuan Province, China
4. Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
5. Department of Internal Medicine, Traditional Chinese Medicine Hospital of Fushun County, Fushun 643200, Sichuan Province, China
6. Department of Acupuncture & Moxibustion, Sichuan Second Traditional Chinese Medicine Hospital, Chengdu 610031, Sichuan Province, China
7. Department of Gerontology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
8. Sichuan Neo-Green Pharmaceutical Technology Development Co., Ltd., Pengzhou 611930, Sichuan Province, China
*The authors made equal contributions to this study.

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Citation:
Tu X, Wang HB, Huang Q, Cai Y, Deng YP, Yong Z, Hu Q, Feng J, Jordan JB, Zhong S. Screening Study on the Anti-Angiogenic Effects of Traditional Chinese Medicine - Part II: Wild Chrysanthemum. J Cancer 2021; 12(1):124-133. doi:10.7150/jca.52971. Available from https://www.jcancer.org/v12p0124.htm

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Abstract

Background and Aims: Part 2 of our ongoing research with anti-angiogenic effects focuses on Wild chrysanthemum; a heat-clearing and detoxicating Traditional Chinese Medicine (TCM). We screened six heat-clearing and detoxicating TCM and noticed that wild chrysanthemum has a potent anti-angiogenic effect in zebrafish. This study aims to determine the genetic mechanisms underlying the anti-angiogenic effects of wild chrysanthemum.

Methods: Wild chrysanthemum was decocted, concentrated, sieved and desiccated to attain the water extract. 200μg/mL wild chrysanthemum water extract (WCWE) was diluted in 0.1% dimethyl sulfoxide (DMSO) and given to zebrafish via fish water. 48h post-fertilization (hpf) fli1a-EGFP transgenic zebrafish were used to assay angiogenesis. mRNA-seq, qRT-PCR assay and a parallel reaction monitor (PRM) were carried out to reveal the underlying mechanisms.

Results: WCWE showed a significant anti-angiogenic effect in zebrafish. The results of mRNA-seq showed that there were 1119 genes up-regulated and 1332 genes down-regulated by WCWE. The bioinformatic analysis based on mRNA-seq demonstrated that the proteasome signaling pathway was significantly down-regulated. The results of the qRT-PCR assay were consistent with those of the mRNA-seq assay. The results of the PRM assay showed that nine proteins involved in proteasome signaling and the protein expression level of ctnnb2 were significantly down-regulated. The results of the KEGG pathway analysis based on PRM assay demonstrated that WCWE may have an inhibitory action on the regulatory particle of the proteasome.

Conclusion: Wild chrysanthemum has a significant anti-angiogenic effect in zebrafish and it may have an inhibitory action on the regulatory particle of the proteasome. The mechanisms underlying the anti-angiogenic effects of wild chrysanthemum may be related to the down-regulation of proteasome/β-catenin signaling in zebrafish.

Keywords: wild chrysanthemum, zebrafish, angiogenesis, proteasome, β-catenin, Traditional Chinese Medicine