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

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.

Exploration of the active components and pharmacological mechanism of Compound Longmaining for the treatment of myocardial infarction.

Background: Myocardial Infarction (MI) is a cardiovascular disease with a high morbidity and mortality rate. While MI is currently treated with pharmaceuticals, there is a need for new treatment options: compound Chinese medicines may have unique advantages for the treatment of MI. Methods: A combination of network pharmacology and experimental verification is used to identify the ingredients and mechanism of Compound Longmaining (CLMN) for treating MI. Network pharmacology combined with the gene expression omnibus (GEO) chip method is used to analyze the primary pathway of CLMN for treating MI, and then molecular docking is used to verify the affinity of key target proteins in the primary pathway that bind to active molecules. The major active compounds of CLMN are screened using the docking score results. The CIBERSORT algorithm is used to evaluate immune cell infiltration in MI, and high performance liquid chromatography (HPLC) is used to control the quality of the components. Finally, a mouse model is established to verify the molecular mechanism of CLMN for treating MI using hematoxlyn eosin (HE) staining and immunohistochemistry. Results: By utilizing network pharmacology combined with molecular docking, the mechanism of action of CLMN for the treatment of MI was found to possibly be related to the ingredients of puerarin, daidzein, ferulic acid, chrysin, and galangin. These molecules regulate the NF-Kappa B signaling pathway and the expression of RELA, IKBKB, NKBIA, and other targets. The CIBERSORT algorithm and ggplot2 package analysis were used to distinguish the immune cells, such as neutrophils, macrophages, and T cells, that play a key role in the development of MI. HPLC controlled the quality of the screened medicinal ingredients. An immunohistochemical analysis showed that the TNF-α and TRAF-2 expression levels in MI of the CLMN-treated mice were decreased, while IkBα was increased. HE staining showed CLMN reduced inflammation in mouse cardiomyocytes and decreased fibrosis. Conclusions: This study showed that CLMN treatment of MI is a process that involves multi-components, multi-targets and multi-pathways, and the established multi-index component content measurement of the CLMN decoction can be used for quality control of CLMN.