Study of the Mechanism of Antiemetic Effect of Lavandula angustifolia Mill. Essential Oil Based on Ca2+/CaMKII/ERK1/2 Pathway

Drug Des Devel Ther. 2022 Jul 26:16:2407-2422. doi: 10.2147/DDDT.S366597. eCollection 2022.

Abstract

Purpose: 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; mechanism validation; molecular docking; vomiting; weight coefficient.

MeSH terms

  • Acetates
  • Animals
  • Antiemetics* / pharmacology
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Lavandula* / chemistry
  • MAP Kinase Signaling System
  • Molecular Docking Simulation
  • Oils, Volatile* / chemistry
  • Oils, Volatile* / pharmacology
  • Rats
  • Serotonin
  • Substance P

Substances

  • Acetates
  • Antiemetics
  • Oils, Volatile
  • Serotonin
  • Substance P
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium

Grants and funding

This study was supported by the Science and Technology Project of Jiangxi Provincial Department of Education (GJJ150877), the Training plan for young teachers in key disciplines of Jiangxi University of Chinese Medicine (51000112), the 2017 Open Fund of the Key Laboratory of Modern Chinese Medicine Preparation by the Ministry of Education (2017003), the Project of Shaanxi Provincial Department of science and technology (2022JM-555), the Key R & D program of Xianyang City (2021ZDYF-SF-0015), the National Natural Science Foundation of China (Grant no. 82074026), the Education Department of Shaanxi Provincial Government of China (20JK0588), the Shaanxi Provincial Key Laboratory Project of Traditional Chinese Medicine (KF2204), the National Natural Science Foundation of China (81703720), the Scientific Research in the affiliated Hospital of Shaanxi University of Chinese Medicine (2020ZJ005) and the Shaanxi Provincial Key Research and Development Program (2017SF-351).