Drug Design, Development and Therapy (Dec 2021)
Pro-Angiogenic Effects of Essential Oil from Perilla frutescens and Its Main Component (Perillaldehyde) on Zebrafish Embryos and Human Umbilical Vein Endothelial Cells
Abstract
Fei Zhou,1,2,* Ou Dai,1,2,* Cheng Peng,1,2 Liang Xiong,1– 3 Hui Ao,1,4 Fei Liu,1– 3 Qin-Mei Zhou1,3,4 1State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 2School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 3Institute of Innovative Medicine Ingredients of Southwest Specialty Medicinal Materials, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China; 4Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng Peng; Qin-Mei Zhou Tel +86 28 61800005; +86 28 61800231Email [email protected]; [email protected]: 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
