Study of the Mechanism of Antiemetic Effect of Mill. Essential Oil Based on Ca/CaMKII/ERK1/2 Pathway.

PURPOSE

To investigate the effective components and possible mechanism of action of 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-HTR, 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-HTR, 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 Ca/CaMKII/ERK1/2 pathway of the cAMP signaling pathway.