The Mechanism Action of German Chamomile (Matricaria recutita L.) in the Treatment of Eczema: Based on Dose-Effect Weight Coefficient Network Pharmacology

Abstract

To determine the active ingredients in German chamomile volatile oil and the mechanism of action in the treatment of eczema, this study used two parameters (ingredient content and oil-water partition coefficient) and established a new network pharmacology method based on the dose-effect weight coefficient. Through the new network pharmacology method, we found that German chamomile volatile oil regulated T-cell lymphatic subpopulations to inhibit the Th17 cell differentiation signaling pathway. This resulted in a reduction of interleukin 17 (IL-17), thereby inhibiting the activation of the nuclear factor kappa beta (NF-κB) and MAPK pathways, decreasing the secretion of the pro-inflammatory factors (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)), and reducing inflammation. In this study, a new dose-effect relationship synergistic network pharmacology method was established to provide a new method for the screening of effective ingredients and pathways of drugs, and to provide a basis for the follow-up studies of German chamomile volatile oil in the treatment of eczema.

Keywords: German chamomile; eczema; mechanism verification; molecular docking; weight coefficient.

GRAPHICAL ABSTRACT

FIGURE 1

(A) Total ion current diagram of volatile oil of German chamomile. (B) Eczema differential gene volcano map. (C): Intersection map of German chamomile volatile oil target, eczema target, and differential gene. (D) Volatile oil composition of German chamomile target map. (E) PPI network diagram of key targets. (F,H) Enrichment results of BP and KEGG before sorting, respectively. (G,I) Enrichment results after sorting BP and KEGG.

FIGURE 2

(A–T) Chemical structures of 20 active components.

FIGURE 3

(A): Effects of volatile oil of German chamomile on back inflammation in mice (A1: normal group, A 2: model group, A 3: positive drug group, A 4: low-dose German chamomile group, A 5: middle-dose German chamomile group, and A 6: high-dose German chamomile group). (B): Mice skin sebum content test results. (C): Mice skin water content results. (D): Mice skin elasticity test results. (E): Mice spleen index measurement results (note: data are expressed as mean ± SD (n = 6), compared with the normal group #p < 0.05, ##p < 0.01, compared with the model group *p < 0.05, **p < 0.01).

FIGURE 4

(A) H&E staining results of mice skin tissue. (B) Mast cell count by toluidine blue staining. (C) CD4 cell staining results. (D) CD8 cell staining results (note 1: normal group, 2: model group, 3: positive drug group, 4: low-dose group, 5: middle-dose group, and 6: high-dose group). (E) Immunohistochemical detection of CD4 cell expression in skin lesions on the back of mice. (F) Immunohistochemical detection of CD8 cell expression in skin lesions on the back of mice (note: data are expressed as mean ± SD (n = 3) compared with the normal group ##p < 0.01, compared with the model group, *p < 0.05, **p < 0.01).

FIGURE 5

(A) ELISA detection of TNF-α. (B) the ELISA detection of IL-6. (C) ELISA detection of IL-17 (note: the data are expressed as the mean ± SD (n = 3), compared with the normal group ##p < 0.01, compared with the model group, *p < 0.05, **p < 0.01). (D–I) Western blot was used to detect the protein expression levels of p-p38, p38, p-p65, p65,p-p38/p38, and p-p65/p65. (D,E) Quantitative protein expression levels of p-p38, p38, p-p65, and p65. (F,G) Protein expression level of p38, p-P38, p65, and p-P65. (H,I) Ratio of p-P38/p38 and p-P65/p65 in mouse skin lesions. (x¯±s (n = 3), compared with the normal group ###p < 0.001, ##p < 0.01, compared with the model group ***p < 0.001,*p < 0.05).

FIGURE 6

(A–C) Results of docking of JAK3 and components (Z)-ene-yne-dicycloether, bisabolol oxide A, (-)-α-bisabolol oxide B. (D–F) Results of docking of PKC8 and components germacrene D, γ-elemene, and β-copaene. (G–I) Results of docking of RORC target with components germacrene D, chamazulene, and cedr-8-ene. (J) IL6 target and component naphthalene, 1,2,3,4,4a, 7-hexahydro-1,6-dimethyl-4-(1-methylethyl)- docking result. (K) ZAP70 target and component naphthalene, 1,2,3,4,4a, 7-hexahydro-1,6-dimethyl-4-(1-methylethyl)- docking result. (L) Comprehensive heat map display.

FIGURE 7

Mechanism display.