Pro-Angiogenic Effects of Essential Oil from Perilla frutescens and Its Main Component (Perillaldehyde) on Zebrafish Embryos and Human Umbilical Vein Endothelial Cells

Abstract

Purpose

Perilla frutescens (L.) Britt., a traditional edible-medicinal herb in China, has been used to treat cardiovascular and cerebrovascular (cardio-cerebrovascular) diseases for thousands of years. However, knowledge of the mechanisms underlying the effects of essential oil from P. frutescens (EOPF) in the treatment of cardio-cerebrovascular diseases is lacking. The promotion of angiogenesis is beneficial in the treatment of ischemic cardio-cerebrovascular diseases. The current study investigated the pro-angiogenic role of EOPF and its main component perillaldehyde in sunitinib-injured transgenic Tg (flk1:EGFP) zebrafish embryos and human umbilical vein endothelial cells (HUVECs) for the first time.

Materials and Methods

The pro-angiogenic effects of EOPF and perillaldehyde were observed in vivo using transgenic Tg (flk1:EGFP) zebrafish embryos and in vitro using HUVECs. Cell viability, proliferation, migration, tube formation, and protein levels were detected by MTT, EdU staining, wound healing, transwell chamber, and Western blot assays, respectively.

Results

EOPF and perillaldehyde exerted a significant stimulatory effect on the formation of zebrafish intersegmental vessels (ISVs). Moreover, EOPF and perillaldehyde promoted proliferation, migration, and tube formation in sunitinib-treated HUVECs. Additionally, our findings uncovered that the pro-angiogenic effects of EOPF and perillaldehyde were mediated by increases in the expression ratios of p-ERK1/2 to ERK1/2 and Bcl-2 to Bax.

Conclusion

The present study is the first report to provide clear evidence that EOPF and perillaldehyde promote angiogenesis by stimulating repair of sunitinib-injured ISVs in zebrafish embryos and promoting proliferation, migration, and tube formation in sunitinib-injured HUVECs. The underlying mechanisms are related to increased p-ERK1/2 to ERK1/2 and Bcl-2 to Bax expression ratios. EOPF and perillaldehyde may be used in the treatment of cardio-cerebrovascular diseases, which is consistent with the traditional application of P. frutescens.

Keywords:

• Perilla frutescens
• essential oil
• perillaldehyde
• pro-angiogenesis
• HUVECs
• zebrafish

Acknowledgments

This work was supported by the Applied Basic Research Project of Sichuan Province (Grant Nos. 2019YJ0334 and 2018JY0269), the Key Science and Technology Project of Sichuan Province (Grant No. 2018JZ0081), the Youth Teachers Innovation Program of Chengdu University of Traditional Chinese Medicine (Grant No. ZRQN2018015), and the “Xing Lin Scholar” Plan of Chengdu University of Traditional Chinese Medicine (Grant Nos. YXRC2018005, BSH2018009, BSH2019028, and QNXZ2019030).

Disclosure

The authors declare no conflicts of interest.