Vaccarin promotes endothelial cell proliferation in association with neovascularization in vitro and in vivo

Xie,Fengshan; Feng,Lei; Cai,Weiwei; Qiu,Yuyu; Liu,Yanling; Li,Yue; Du,Bin; Qiu,Liying

doi:10.3892/mmr.2015.3503

Vaccarin promotes endothelial cell proliferation in association with neovascularization in vitro and in vivo

Authors:
- Fengshan Xie
- Lei Feng
- Weiwei Cai
- Yuyu Qiu
- Yanling Liu
- Yue Li
- Bin Du
- Liying Qiu
View Affiliations

Affiliations: Laboratory of Natural Medicine, School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China
Published online on: March 18, 2015 https://doi.org/10.3892/mmr.2015.3503
Pages: 1131-1136

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Angiogenesis is a major pathological component of several diseases, including traumatic vascular disease and coronary heart disease. The purpose of the present study was to determine the effects of vaccarin on endothelial cell migration and neovascularization, which are important and necessary components of wound healing. The present study investigated and confirmed neovascularization induced by vaccarin in vitro and in vivo. In vitro, the effects of vaccarin (1.08 and 2.15 µM) on proliferation, migration and tube formation of human microvascular endothelial cells (HMEC)‑1 were evaluated via sulforhodamine B assay and migration and tube formation assay, respectively. Furthermore, a mouse Matrigel plus model was used to detect capillary‑like tube structures in vivo. Immunohistochemistry was used to detect the protein expression of cluster of differentiation 31 (CD31), p‑AKT and p‑extracellular‑signal‑regulated kinases (Erk). Vaccarin significantly promoted HMEC‑1 proliferation and migration and tube formation of HMEC‑1 at a dose of 2.15 µM. In vivo, vaccarin delivered by daily oral administration significantly improved epidermal growth factor‑induced angiogenesis in an intradermal inoculation mouse model. The mouse Matrigel model study also revealed that vaccarin significantly promoted neovascularization via detection of CD31 levels and enhanced protein expression of p‑Akt and p‑Erk. In addition, vaccarin also promoted expression of CD31.

View Figures

View References

1	China Pharmacopoeia Committee: Chinese Pharmacopoeia. 1. 2010, China Medical Science Press; Beijing, China: pp. 49–50. 2010
2	Sang SM, Lao A, Chen ZL, Uzawa J and Fujimoto Y: Chemistry and bioactivity of the seeds of Vaccaria segetalis. Oriental Foods and Herbs: Chemistry and Health Effects. 859. Ho C, Lin J and Zheng Q: American Chemical Society; Washington DC, WA: pp. 279–291. 2003, View Article : Google Scholar
3	Li F and Liang JY: Research progress of Vaccaria segetalis. Straits Pharm J. 3:1–5. 2007.
4	Koike K, Jia Z and Nikaido T: Triterpenoid saponins from Vaccaria segetalis. Phytochemistry. 47:1343–1349. 1998. View Article : Google Scholar : PubMed/NCBI
5	Sang SM, Lao AN and Wang HC: A phenylpropanoid glycoside from Vaccaria segetalis. Phytochemistry. 48:569–571. 1998. View Article : Google Scholar
6	Sang S, Lao A, Wang H, et al: Triterpenoid saponins from Vaccaria segetalis. J Asian Nat Prod Res. 1:199–205. 1999. View Article : Google Scholar
7	Yun YS, Morita H, Takeya K, et al: Cyclic peptides from higher plants. 34. segetalins G and H, structures and estrogen-like activity of cyclic pentapeptides from Vaccaria segetalis. J Nat Prod. 60:216–218. 1997. View Article : Google Scholar : PubMed/NCBI
8	Morita H, Yun YS, Takeya K, et al: A cyclic heptapeptide from Vaccaria segetalis. Phytochemistry. 42:439–441. 1996. View Article : Google Scholar : PubMed/NCBI
9	Dong Z and Chen N: Study on the TLC identification method of Wangbuliuxing tablets. China For Med Treat. 30:1282011.In Chinese.
10	Li N, Ma CH, Liu D, et al: Chemical constituents analysis of fried Vaccaria segetalis. Chin J Exptl Tradit Med Form. 19:73–75. 2013.
11	Sun Y, Liang H, Zhang X, et al: Structural elucidation and immunological activity of a polysaccharide from the fruiting body of Armillaria mellea. Bioresour Technol. 100:1860–1863. 2009. View Article : Google Scholar
12	Sun Y, Wang S, Li T, et al: Purification, structure and immuno-biological activity of a new water-soluble polysaccharide from the mycelium of Polyporus albicans (Imaz) Teng. Bioresour Technol. 99:900–904. 2008. View Article : Google Scholar
13	Meng H, Chen Y, Qin W, et al: Determination of vaccarin in Vaccariae Semen by HPLC. Zhongguo Zhong Yao Za Zhi. 35:2072–2074. 2010.In Chinese. PubMed/NCBI
14	Folkman J: Angiogenesis. Annu Rev Med. 57:1–18. 2006. View Article : Google Scholar : PubMed/NCBI
15	Folkman J: Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov. 6:273–286. 2007. View Article : Google Scholar : PubMed/NCBI
16	Vita JA: Endothelial function and clinical outcome. Heart. 91:1278–1279. 2005. View Article : Google Scholar : PubMed/NCBI
17	Rosengart TK, Patel SR and Crystal RG: Therapeutic angiogenesis: protein and gene therapy delivery strategies. J Cardiovasc Risk. 6:29–40. 1999.PubMed/NCBI
18	Kang Z, Jiang W, Luan H, Zhao F and Zhang S: Cornin induces angiogenesis through PI3K-Akt-eNOS-VEGF signaling pathway. Food Chem Toxicol. 58:340–346. 2013. View Article : Google Scholar : PubMed/NCBI
19	Min JK, Han KY, Kim EC, et al: Capsaicin inhibits in vitro and in vivo angiogenesis. Cancer Res. 64:644–651. 2004. View Article : Google Scholar : PubMed/NCBI
20	Malinda KM: In vivo matrigel migration and angiogenesis assay. Methods Mol Biol. 467:287–294. 2009.PubMed/NCBI
21	Weidner N: Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 36:169–180. 1995. View Article : Google Scholar : PubMed/NCBI
22	Adini A, Fainaru O, Udagawa T, Connor KM, Folkman J and D’Amato RJ: Matrigel cytometry: a novel method for quantifying angiogenesis in vivo. J Immunol Methods. 342:78–81. 2009. View Article : Google Scholar
23	Takeuchi K, Yanai R, Kumase F, Morizane Y, Suzuki J, Kayama M, et al: EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay. PLoS One. 9:e918492014. View Article : Google Scholar : PubMed/NCBI
24	Kakisis JD, Liapis CD, Breuer C, et al: Artificial blood vessel: the holy grail of peripheral vascular surgery. J Vasc Surg. 41:349–354. 2005. View Article : Google Scholar : PubMed/NCBI
25	Sang SM, Lao AN, Leng Y, et al: A new triterpenoid saponin with inhibition of luteal cell from the seeds of Vaccaria Segetalis. J Asian Nat Prod Res. 4:297–301. 2002. View Article : Google Scholar : PubMed/NCBI
26	Sang SM, Lao AN, Chen ZL, et al: Three new triterpenoid saponins from the seeds of Vaccaria Segetalis. J Asian Nat Prod Res. 2:187–193. 2000. View Article : Google Scholar
27	Goodwin AM: In vitro assays of angiogenesis for assessment of angiogenic and anti-angiogenic agents. Microvasc Res. 74:172–183. 2007. View Article : Google Scholar : PubMed/NCBI
28	Kowanet M and Ferrara N: Vascular endothelial growth factor signaling pathways: Therapeutic perspective. Clin Cancer Res. 12:5018–5022. 2006. View Article : Google Scholar