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

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 cardiocerebrovascular diseases. The current study investigated the pro-angiogenic role of EOPF and its main component perillaldehyde in sunitinib-injured transgenic Tg (flk1:EGFP) zebra fish 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 Bcl2 to Bax expression ratios. EOPF and perillaldehyde may be used in the treatment of cardiocerebrovascular diseases, which is consistent with the traditional application of P. frutescens.

Automated summary

Perilla frutescens essential oil and its main component perillaldehyde demonstrate significant pro-angiogenic effects by promoting formation of intersegmental vessels in zebrafish embryos and proliferation, migration, and tube formation in sunitinib-injured HUVECs. These effects are mediated by increased expression ratios of p-ERK1/2 to ERK1/2 and Bcl2 to Bax. These findings suggest that EOPF and perillaldehyde may be potential therapies for cardiocerebrovascular diseases.