Drug Design, Development and Therapy (Jul 2022)
Study of the Mechanism of Antiemetic Effect of Lavandula angustifolia Mill. Essential Oil Based on Ca2+/CaMKII/ERK1/2 Pathway
Abstract
Jia Li,1,* Xiao Wang,1,* Shining Xun,2,* Qiuting Guo,3 Yao Wang,1 Yanzuo Jia,1 Wenfei Wang,1 Yujiao Wang,1 Taotao Li,1 Tiantian Tang,1 Junbo Zou,1 Mei Wang,1 Ming Yang,4 Fang Wang,4 Xiaofei Zhang,1,4 Changli Wang1 1Department of Pharmaceutics, The Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 2Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 3Xianyang Vocational Technical College, Xianyang, People’s Republic of China; 4Department of Pharmaceutics, Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaofei Zhang, Department of Pharmaceutics, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China, Tel +86 177 7003 7322, Fax +86 29-38185333, Email [email protected] Changli Wang, Department of Pharmaceutics, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China, Tel +86 132 3910 3433, Email [email protected]: To investigate the effective components and possible mechanism of action of Lavandula angustifolia Mill. essential oil (LEO) in preventing vomiting through the olfactory pathway.Materials and Methods: A new network pharmacology–based method was established to analyze main components and pathways of LEO involved in antiemetic effects by introducing component content; biological activities of key proteins of the olfactory pathway and their corresponding compounds were verified by molecular docking technique; and finally pica in a rat model was established to verify the molecular mechanism of antiemetic effects of LEO by enzyme-linked immunosorbent assay (ELISA) to determine the serum 5-HT, substance P, and DA levels in each group and by immunohistochemistry to determine the contents of 5-HT3R, CaMKII and ERK1/2 proteins in the medulla oblongata tissue.Results: Network pharmacology combined with molecular docking analysis showed that the mechanism of the antiemetic effect of LEO may be related to (2Z)-3,7-dimethyl-2,6-octadienyl acetate, linalyl acetate, butanoic acid, hexyl ester, 4-hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, acetate, .tau.-cadinol and other active ingredients, which regulate the cyclic adenosine monophosphate (cAMP) signaling pathway and the expression of BRAF, PDE and other targets on the pathway. An ELISA revealed that LEO reduced the levels of 5-hydroxytryptamine (5-HT), substance P, and dopamine in serum compared with the model group (P < 0.05). Immunohistochemical analysis showed that LEO decreased the expression of 5-HT3R, CaMKII, and ERK1/2 proteins in the medulla oblongata of rats compared with the model group (P < 0.01).Conclusion: LEO may achieve the antiemetic effect by reducing the content of 5-HT and inhibiting its related receptors, thereby regulating downstream Ca2+/CaMKII/ERK1/2 pathway of the cAMP signaling pathway.Keywords: Lavandula angustifolia Mill, vomiting, weight coefficient, molecular docking, mechanism validation
