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

Figures & data

Figure 1 A detailed flowchart of the study.

Table 1 Qualitative Results of Lavandula angustifolia Mill. Essential Oil by GC-MS

Number	Chemical Composition^a	Retention Time(Min)	Pct Total^b (%)	Retention Index
1	beta.-Myrcene	6.05	7.69	990.80
2	Tricyclo[2.2.1.02,6]heptane, 1,7,7-trimethyl-	7.04	7.26	1053.85
3	1,3,6-Octatriene, 3,7-dimethyl-, (Z)-	7.43	5.39	1090.00
4	1,6-Octadien-3-ol, 3,7-dimethyl-	9.02	22.39	1118.95
5	1-Octen-1-ol, acetate	9.06	0.97	1120.96
6	2,4,6-Octatriene, 3,4-dimethyl-	9.38	4.66	1136.69
7	4-Hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, (R)-	10.23	3.04	1177.42
8	Borneol	10.29	1.54	1180.64
9	3-Cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-	10.47	4.02	1189.11
10	Butanoic acid, hexyl ester	10.57	1.17	1193.95
11	3-Cyclohexene-1-methanol, .alpha., .alpha.,4-trimethyl-, (R)-	10.73	2.12	1202.40
12	Linalyl acetate	11.89	15.80	1268.75
13	4-Hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, acetate	12.35	4.37	1295.67
14	(2Z)-3,7-Dimethyl-2,6-octadienyl acetate	13.45	2.11	1367.95
15	Geranyl acetate	13.75	3.06	1387.84
16	Caryophyllene	14.42	5.56	1435.58
17	alpha.-Humulene	14.84	0.81	1466.87
18	(-)-Germacrene D	15.20	0.93	1493.25
19	Naphthalene, 1,2,3,4,4a,5,6,8a-octahydro-7-methyl-4-methylene-1-(1-methylethyl)-,(1.alpha.,4a.beta.,8a.alpha.)-	15.62	0.57	1525.99
20	Caryophyllene oxide	16.57	1.73	1791.66
21	tau.-Cadinol	17.23	1.07	1858.69

Notes: ^aThe components identified in the highest yields are in bold; ^bThe area percentage contribution of each component to total peak area; bold, the key components of LEO for antiemetic or high content.

Figure 2 (A) lon current diagram of LEO. (B) Active ingredient–target, disease–target, and OR–target Venn diagram. (C) PPI network diagram. (D) LEO active component–core target interaction network diagram.

Figure 3 (A and C) Biological process-BP of LEO before and after ranking by weight coefficient algorithm. (B and D) KEGG enrichment analysis of target compounds in LEO before and after ranking by weight coefficient algorithm.

Table 2 Docking Scores of Target Proteins with Their Corresponding Compounds and Positive Controls

Key Target	Small Molecule Ligand	Docking Score	Positive for Drugs	Docking Score
PDE10A	Linalyl acetate	72.633	Triflusal	75.0956
	Butanoic acid, hexyl ester	76.5093
PDE4B	4-Hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, acetate	75.9296	Papaverine	76.9027
PDE4D	tau.-Cadinol	74.344	Roflumilast	69.4846
BRAF	(2Z)-3,7-Dimethyl-2,6-octadienyl acetate	72.5814	Regorafenib	68.9849

Figure 4 Docking results of key target proteins with their corresponding compounds. (A) PDE10A and Linalyl acetateinteraction diagram. (B) PDE10A and Butanoic acid, hexyl esterinteraction diagram. (C) PDE4B and 4-Hexen-1-ol, 5-methyl-2-(1-methylethenyl)-, acetateinteraction diagram. (D) PDE4D and .tau.-Cadinolinteraction diagram. (E) BRAF and (2Z)-3,7-dimethyl-2,6-octadienyl acetate interaction diagram.

Figure 5 Effects of LEO on cisplatin-induced kaolin and food consumption and body weight of rats (n = l0). (A) Kaolin consumption, (B) Food consumption, and (C) Body weight. The data represent the mean ± standard error. The data were analyzed using two-way ANOVA, followed by Tukey’s post hoc test. *P < 0.05, **P < 0.01 vs control group; ^#P < 0.05, ^##P < 0.01 vs model group, Cisplatin was administrated at 0 h.

Figure 6 Effects of LEO on 5-HT, substance P, and dopamine levels in serum of model rat. (A) Effect of LEO on 5-HT contents in cisplatin-treated rat serum, (B) Effect of LEO on substance P contents in cisplatin-treated rat serum, and (C) Effect of LEO on dopamine contents in cisplatin-treated rat serum. *P < 0.05, ** P < 0.01 vs control group; ^#P < 0.05, ^##P < 0.01 vs model group.

Figure 7 Effects of LEO pretreatment on the expression of 5-HT₃R, CaMKII, and ERK1/2 protein in the medulla oblongata tissue of rats with vomiting (Immunohistochemistry, 100), and the changes of 5-HT₃R, CaMKII, and ERK1/2 protein expression in the medulla oblongata tissue. *P < 0.05, **P < 0.01 vs control group; ^#P < 0.05, ^##P < 0.01 vs model group.

Figure 8 Mechanism display of LEO suppressed vomiting via Ca²⁺/CaMKII/ERK1/2 signaling pathway. *P < 0.05, **P < 0.01 vs control group; ^#P < 0.05, ^##P < 0.01 vs model group.