Full Text:   <382>

Summary:  <30>

CLC number: 

On-line Access: 2022-05-13

Received: 2021-12-13

Revision Accepted: 2022-02-14

Crosschecked: 2022-05-13

Cited: 0

Clicked: 453

Citations:  Bibtex RefMan EndNote GB/T7714


Huayi LIU


Yijia MAO


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.5 P.353-364


Therapeutic potential of traditional Chinese medicine for vascular endothelial growth factor

Author(s):  Yijia MAO, Lingkai MENG, Huayi LIU, Yuting LU, Kuo YANG, Guangze OUYANG, Yanran BAN, Shuang CHEN

Affiliation(s):  Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301608, China; more

Corresponding email(s):   15900369830@163.com

Key Words:  Vascular endothelial growth factor (VEGF), VEGF receptor, Traditional Chinese medicine (TCM)

Share this article to: More |Next Article >>>

Yijia MAO, Lingkai MENG, Huayi LIU, Yuting LU, Kuo YANG, Guangze OUYANG, Yanran BAN, Shuang CHEN. Therapeutic potential of traditional Chinese medicine for vascular endothelial growth factor[J]. Journal of Zhejiang University Science B, 2022, 23(5): 353-364.

@article{title="Therapeutic potential of traditional Chinese medicine for vascular endothelial growth factor",
author="Yijia MAO, Lingkai MENG, Huayi LIU, Yuting LU, Kuo YANG, Guangze OUYANG, Yanran BAN, Shuang CHEN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Therapeutic potential of traditional Chinese medicine for vascular endothelial growth factor
%A Yijia MAO
%A Lingkai MENG
%A Huayi LIU
%A Yuting LU
%A Guangze OUYANG
%A Yanran BAN
%A Shuang CHEN
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 5
%P 353-364
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2101055

T1 - Therapeutic potential of traditional Chinese medicine for vascular endothelial growth factor
A1 - Yijia MAO
A1 - Lingkai MENG
A1 - Huayi LIU
A1 - Yuting LU
A1 - Kuo YANG
A1 - Guangze OUYANG
A1 - Yanran BAN
A1 - Shuang CHEN
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 5
SP - 353
EP - 364
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2101055

vascular endothelial growth factor (VEGF) is the main regulator of physiological angiogenesis during embryonic development, bone growth, and reproductive function, and it also participates in a series of pathological changes. traditional Chinese medicine (TCM), with a history of more than 2000 years, has been widely used in clinical practice, while the exploration of its mechanisms has only begun. This review summarizes the research of recent years on the influence of TCM on VEGF. It is found that many Chinese medicines and recipes have a regulatory effect on VEGF, indicating that Chinese medicine has broad prospects as a complementary and alternative therapy, providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]AhluwaliaA, TarnawskiAS, 2012. Critical role of hypoxia sensor-HIF-1α in VEGF gene activation. Implications for angiogenesis and tissue injury healing. Curr Med Chem, 19(1):90-97.

[2]AoLM, GaoH, JiaLF, et al., 2022. Matrine inhibits synovial angiogenesis in collagen-induced arthritis rats by regulating HIF-VEGF-Ang and inhibiting the PI3K/Akt signaling pathway. Mol Immunol, 141:13-20.

[3]CaiGX, LiuBY, LiuW, et al., 2007. Buyang Huanwu Decoction can improve recovery of neurological function, reduce infarction volume, stimulate neural proliferation and modulate VEGF and Flk1 expressions in transient focal cerebral ischaemic rat brains. J Ethnopharmacol, 113(2):292-299.

[4]ChaoYH, YangWT, LiMC, et al., 2021. Angelica dahurica and Rheum officinale facilitated diabetic wound healing by elevating vascular endothelial growth factor. Am J Chin Med, 49(6):1515-1533.

[5]ChenH, ChedotalA, HeZG, et al., 1997. Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III. Neuron, 19(3):547-559.

[6]ChenZZ, GongX, 2017. Effect of Hua Yu Xiao Zheng decoction on the expression levels of vascular endothelial growth factor and angiopoietin‑2 in rats with endometriosis. Exp Ther Med, 14(6):5743-5750.

[7]ChenZZ, GongX, GuoQ, et al., 2019. Bu Yang Huan Wu decoction prevents reperfusion injury following ischemic stroke in rats via inhibition of HIF-1α, VEGF and promotion β-ENaC expression. J Ethnopharmacol, 228:70-81.

[8]Chinese Materia Medica Commission of the National Administration of Traditional Chinese Medicine, 1999. The Chinese Materia Medica-Part 2. Shanghai Scientific & Technical Publishers, Shanghai, China(in Chinese)

[9]Chinese Pharmacopoeia Commission, 2020. Pharmacopoeia of the People’s Republic of China (Part 1). China Medical Science Press, Beijing, China(in Chinese).

[10]ConnollyDT, OlanderJV, HeuvelmanD, et al., 1989. Human vascular permeability factor: isolation from U937 cells. J Biol Chem, 264(33):20017-20024.

[11]DaiJ, RabieABM, 2007. VEGF: an essential mediator of both angiogenesis and endochondral ossification. J Dent Res, 86(10):937-950.

[12]DaiXJ, LiuDM, LiuMX, et al., 2017. Anti-metastatic efficacy of traditional Chinese medicine (TCM) ginsenoside conjugated to a VEFGR-3 antibody on human gastric cancer in an orthotopic mouse model. Anticancer Res, 37(3):979-986.

[13]de AlmodovarCR, LambrechtsD, MazzoneM, et al., 2009. Role and therapeutic potential of VEGF in the nervous system. Physiol Rev, 89(2):607-648.

[14]DonnezJ, SmoesP, GillerotS, et al., 1998. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod, 13(6):1686-1690.

[15]DuongT, KoltowskaK, Pichol-ThievendC, et al., 2014. VEGFD regulates blood vascular development by modulating SOX18 activity. Blood, 123(7):1102-1112.

[16]DuranCL, BorrielloL, KaragiannisGS, et al., 2021. Targeting Tie2 in the tumor microenvironment: from angiogenesis to dissemination. Cancers, 13(22):5730.

[17]FeiXJ, ZhangX, WangQ, et al., 2018. Xijiao Dihuang Decoction alleviates ischemic brain injury in MCAO rats by regulating inflammation, neurogenesis, and angiogenesis. Evid-Based Complement Alternat Med, 2018:5945128.

[18]FerraraN, 2002. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer, 2(10):795-803.

[19]FerraraN, HenzelWJ, 1989. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun, 161(2):851-858.

[20]FerraraN, GerberHP, LecouterJ, 2003. The biology of VEGF and its receptors. Nat Med, 9(6):669-676.

[21]GaoML, GeZP, DengR, et al., 2021. Evaluation of VEGF mediated pro-angiogenic and hemostatic effects and chemical marker investigation for Typhae Pollen and its processed product. J Ethnopharmacol, 268:113591.

[22]HanCY, LiuJ, WanF, et al., 2019. Effects of Tianqijiangtang capsule on survival, self-renewal and differentiation of hippocampal neural stem cells of embryonic rats cultured in high glucose medium. Am J Transl Res, 11(9):5560-5572.

[23]HannanNJ, PaivaP, MeehanKL, et al., 2011. Analysis of fertility-related soluble mediators in human uterine fluid identifies VEGF as a key regulator of embryo implantation. Endocrinology, 152(12):4948-4956.

[24]HerzogY, KalcheimC, KahaneN, et al., 2001. Differential expression of neuropilin-1 and neuropilin-2 in arteries and veins. Mech Dev, 109(1):115-119.

[25]HuGY, YangP, ZengY, et al., 2018. Danggui Buxue decoction promotes angiogenesis by up-regulation of VEGFR1/2 expressions and down-regulation of sVEGFR1/2 expression in myocardial infarction rat. J Chin Med Assoc, 81(1):37-46.

[26]HuangAN, QiX, CuiYM, et al., 2020. Serum VEGF: diagnostic value of acute coronary syndrome from stable angina pectoris and prognostic value of coronary artery disease. Cardiol Res Pract, 2020:6786302.

[27]JiangXM, YanH, ZhongXF, et al., 2020. Effect of Bushen Yutai recipe on IVF patients subjected to mild ovarian stimulation. Front Med, 7:541537.

[28]JingM, BiXJ, YaoXM, et al., 2020. Enhanced antitumor efficacy using epirubicin and schisandrin B co-delivery liposomes modified with PFV via inhibiting tumor metastasis. Drug Dev Ind Pharm, 46(4):621-634.

[29]KanerRJ, LadettoJV, SinghR, et al., 2000. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol, 22(6):657-664.

[30]KarkkainenMJ, HaikoP, SainioK, et al., 2004. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol, 5(1):74-80.

[31]KawasakiT, KitsukawaT, BekkuY, et al., 1999. A requirement for neuropilin-1 in embryonic vessel formation. Development, 126(21):4895-4902.

[32]KeckPJ, HauserSD, KriviG, et al., 1989. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science, 246(4935):1309-1312.

[33]KessenbrockK, PlaksV, WerbZ, 2010. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell, 141(1):52-67.

[34]KimYJ, ChoiWI, JeonBN, et al., 2014. Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance. Toxicology, 322:23-33.

[35]KonopkaA, JanasJ, PiotrowskiW, et al., 2013. Concentration of vascular endothelial growth factor in patients with acute coronary syndrome. Cytokine, 61(2):664-669.

[36]KuchtaK, XiangY, HuangS, et al., 2017. Celastrol, an active constituent of the TCM plant Tripterygium wilfordii Hook.f., inhibits prostate cancer bone metastasis. Prostate Cancer Prostatic Dis, 20(2):156-164.

[37]LeeHP, LiuYC, ChenPC, et al., 2017. Tanshinone IIA inhibits angiogenesis in human endothelial progenitor cells in vitro and in vivo. Oncotarget, 8(65):109217-109227.

[38]LeungDW, CachianesG, KuangWJ, et al., 1989. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science, 246(4935):1306-1309.

[39]LiangC, NiGX, ShiXL, et al., 2020. Astragaloside IV regulates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesis after ischemic stroke. Restor Neurol Neurosci, 38(3):271-282.

[40]LiangC, ZhangT, ShiXL, et al., 2021. Modified Renshen Yangrong decoction enhances angiogenesis in ischemic stroke through promotion of microRNA‍‐‍210 expression by regulating the HIF/VEGF/Notch signaling pathway. Brain Behav, 11(8):e2295.

[41]LinWF, WangH, ZhongMF, et al., 2021. Effect and molecular mechanisms of Jiedu Recipe on hypoxia-induced angiogenesis after transcatheter arterial chemoembolization in hepatocellular carcinoma. Evid-Based Complement Alternat Med, 2021:6529376.

[42]LiuW, ZhangSX, AiB, et al., 2021. Ginsenoside Rg3 promotes cell growth through activation of mTORC1. Front Cell Dev Biol, 9:730309.

[43]LiuX, ChenH, SuGB, et al., 2019. An animal research and a chemical composition analysis of a Chinese prescription for pulmonary fibrosis: Yangfei Huoxue Decoction. J Ethnopharmacol, 245:112126.

[44]OlofssonB, PajusolaK, KaipainenA, et al., 1996. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci USA, 93(6):2576-2581.

[45]PanCF, ZhangX, WangJW, et al., 2020. Weichang’an formula inhibits tumor growth in combination with bevacizumab in a murine model of colon cancer—making up for the deficiency of Bevacizumab by inhibiting VEGFR-1. Front Pharmacol, 11:512598.

[46]PapaioannouAI, KostikasK, KolliaP, et al., 2006. Clinical implications for vascular endothelial growth factor in the lung: friend or foe? Respir Res, 7:128.

[47]ParkJE, ChenHH, WinerJ, et al., 1994. Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem, 269(41):25646-25654.

[48]RamosC, NapoleãoP, SelasM, et al., 2014. Prognostic value of VEGF in patients submitted to percutaneous coronary intervention. Dis Markers, 2014:135357.

[49]ReuterS, GuptaSC, ChaturvediMM, et al., 2010. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med, 49(11):1603-1616.

[50]SengerDR, GalliSJ, DvorakAM, et al., 1983. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science, 219(4587):983-985.

[51]ShibuyaM, 2003. Vascular endothelial growth factor receptor-2: its unique signaling and specific ligand, VEGF-E. Cancer Sci, 94(9):751-756.

[52]SunMY, YeY, XiaoL, et al., 2017. Anticancer effects of ginsenoside Rg3 (Review). Int J Mol Med, 39(3):‍507-518.

[53]TianLL, ShenDC, LiXD, et al., 2016. Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4. Oncotarget, 7(2):1619-1632.

[54]WangSL, TangC, ZhaoH, et al., 2021. Network pharmacological analysis and experimental validation of the mechanisms of action of Si-Ni-San against liver fibrosis. Front Pharmacol, 12:656115.

[55]WangSQ, NanYN, ZhuWH, et al., 2018. Gastrodin improves the neurological score in MCAO rats by inhibiting inflammation and apoptosis, promoting revascularization. Int J Clin Exp Pathol, 11(11):5343-5350.

[56]WangX, LiY, ChenML, et al., 2020. Stepwise rapid tracking strategy to identify active molecules from Ixeris sonchifolia Hance based on “‘affinity mass spectrometry-atomic force microscopy imaging’” technology. Talanta, 217:121031.

[57]WangY, LiJX, WangYQ, et al., 2015. Tanshinone I inhibits tumor angiogenesis by reducing STAT3 phosphorylation at TYR705 and hypoxia-induced HIF-1α accumulation in both endothelial and tumor cells. Oncotarget, 6(18):16031-16042.

[58]WoutersBG, KoritzinskyM, 2008. Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nat Rev Cancer, 8(11):851-864.

[59]XiaC, MengQ, CaoZX, et al., 2006. Regulation of angiogenesis and tumor growth by p110 Alpha and AKT1 via VEGF expression. J Cell Physiol, 209(1):56-66.

[60]XiangYY, YaoXQ, WangX, et al., 2019. Houshiheisan promotes angiogenesis via HIF-1α/VEGF and SDF-1/CXCR4 pathways: in vivo and in vitro. Biosci Rep, 39(10):BSR20191006.

[61]XinMW, HeJQ, YangW, et al., 2018. Wenshen Yangxue decoction improves endometrial receptivity recovery and promotes endometrial angiogenesis in a rat model. Pharm Biol, 56(1):573-579.

[62]XingYY, TuJJ, ZhengLF, et al., 2015. Anti-angiogenic effect of tanshinone IIA involves inhibition of the VEGF/VEGFR2 pathway in vascular endothelial cells. Oncol Rep, 33(1):163-170.

[63]YanYB, LiuLL, DouZY, et al., 2020. Soufeng Yuchuan decoction mitigates the ovalbumin-induced lung damage in a rat model of asthma. Biomed Pharmacother, 125:109933.

[64]YangX, FanWJ, HuangRY, et al., 2021. β‍-Acetoxyisovaleryl alkannin (AAN-II) from Alkanna tinctoria promotes the healing of pressure-induced venous ulcers in a rabbit model through the activation of TGF-‍β/Smad3 signaling. Cell Mol Biol Lett, 26:35.

[65]YuanQ, YaoF, ZhouL, et al., 2019. Yu Ping Feng San exert anti-angiogenesis effects through the inhibition of TSLP-STAT3 signaling pathways in hepatocellular carcinoma. Evid-Based Complement Alternat Med, 2019:1947156.

[66]ZhanY, LiMZ, YangL, et al., 2019. An MRI study of neurovascular restorative after combination treatment with Xiaoshuan enteric-coated capsule and enriched environment in rats after stroke. Front Neurosci, 13:701.

[67]ZhangKJ, ZhuJZ, BaoXY, et al., 2017. Shexiang Baoxin Pills for coronary heart disease in animal models: preclinical evidence and promoting angiogenesis mechanism. Front Pharmacol, 8:404.

[68]ZhangS, TangDC, ZangWH, et al., 2017. Synergistic inhibitory effect of traditional Chinese medicine astragaloside IV and curcumin on tumor growth and angiogenesis in an orthotopic nude-mouse model of human hepatocellular carcinoma. Anticancer Res, 37(2):465-473.

[69]ZhaoL, ZhuXD, NiYQ, et al., 2020. Xiaoyaosan, a traditional Chinese medicine, inhibits the chronic restraint stress-induced liver metastasis of colon cancer in vivo. Pharm Biol, 58(1):1094-1100.

[70]ZhaoZM, LiuHL, SunX, et al., 2017. Levistilide A inhibits angiogenesis in liver fibrosis via vascular endothelial growth factor signaling pathway. Exp Biol Med, 242(9):974-985.

[71]ZhengWL, WangJ, WuJY, et al., 2021. Exploration of the modulatory property mechanism of ELeng Capsule in the treatment of endometriosis using transcriptomics combined with systems network pharmacology. Front Pharmacol, 12:674874.

[72]ZhengWW, QianC, XuFM, et al., 2021. Fuxin Granules ameliorate diabetic nephropathy in db/db mice through TGF-‍β1/Smad and VEGF/VEGFR2 signaling pathways. Biomed Pharmacother, 141:111806.

[73]ZhengXW, ShanCS, XuQQ, et al., 2018. Buyang Huanwu decoction targets SIRT1/VEGF pathway to promote angiogenesis after cerebral ischemia/reperfusion injury. Front Neurosci, 12:911.

[74]ZhouB, YanZP, LiuR, et al., 2016. Prospective study of transcatheter arterial chemoembolization (TACE) with ginsenoside Rg3 versus TACE alone for the treatment of patients with advanced hepatocellular carcinoma. Radiology, 280(2):630-639.

[75]ZhouH, ZhangQ, YangBR, et al., 2019a. Effect of Xiaoliu Decoction on proliferation and apoptosis of endometrial cells in patients with endometriosis. Mod Chin Clin Med, 26(2):52-55 (in Chinese).

[76]ZhouH, ZhangQ, QiC, 2019b. Impact of a Chinese medicinal formula, Xiao Liu Fang, on the “3A” ability of endometrial stromal cells in patients with endometriosis. Mol Ther-Oncolytics, 12:1-8.

[77]ZhouSS, AiZZ, LiWN, et al., 2020. Deciphering the pharmacological mechanisms of Taohe-Chengqi decoction extract against renal fibrosis through integrating network pharmacology and experimental validation in vitro and in vivo. Front Pharmacol, 11:425.

[78]ZhouY, ZhuXP, CuiHM, et al., 2021. The role of the VEGF family in coronary heart disease. Front Cardiovasc Med, 8:738325.

[79]ZhuHH, WangS, ShanC, et al., 2021. Mechanism of protective effect of xuan-bai-cheng-qi decoction on LPS-induced acute lung injury based on an integrated network pharmacology and RNA-sequencing approach. Respir Res, 22:188.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE