Multi-pathway integrated adjustment mechanism of licorice flavonoids presenting anti-inflammatory activity

Abstract

Glycyrrhiza, commonly known as licorice, is a herbal medicine that has been used for thousands of years. Licorice contains multiple flavonoids, which possess a variety of biological activities. On the basis of the anti-inflammatory effects of licorice flavonoids, the potential mechanism of action was investigated via a plasma metabolomics approach. A total of 9 differential endogenous metabolites associated with the therapeutic effect of licorice flavonoids were identified, including linoleic acid, sphingosine, tryptophanamide, corticosterone and leukotriene B4. Besides classical arachidonic acid metabolism, metabolism of sphingolipids, tryptophan and fatty acids, phospholipids synthesis, and other pathways were also involved. The multi-pathway integrated adjustment mechanism of licorice flavonoid action may reduce side effects in patients, along with any anti-inflammatory functions, which provides a foundation for identifying and developing novel, high-potential natural drugs with fewer side effects for clinical application.

Keywords: anti-inflammatory activity; licorice flavonoids; mechanism; multi-pathway.

Copyright © 2019, Spandidos Publications.

Figures

Figure 1.

Effect of licorice flavonoids on formalin-induced mice paw edema. Data are expressed as the mean ± standard deviation (n=9). The ratio of paw edema (%) = [(volume of edema (injected)-volume of edema (normal)]/volume of edema (normal) ×100. *P

Figure 2.

Inhibitory rate of paw edema in different dose groups. Data are expressed as means (n=9). Inhibitory rate (%) = [(Volume of edema (model)-Volume of edema (test)]/Volume of edema (model) ×100. *P

Figure 3.

Content of PGE2 in different groups on formalin-induced mice paw edema. Data are expressed as the mean ± standard deviation (n=9). *P

Figure 4.

Principal component analysis of each group. Each colored point represents a sample. The first, second and third principal components are displayed on the x-, y- and z-axis, respectively. These three components represent the largest fraction of the overall variability. LFL, low dosage group of licorice flavonoids; LFM, middle dosage group of licorice flavonoids; LFH, high dosage group of licorice flavonoids.

Figure 5.

Clustering analysis of the endogenous metabolites in inflammation. The difference in the gray level represents the difference of content. Light gray represents the normal level, dark gray and black represents the content of compound increased or decreased. LFL, low dosage group of licorice flavonoids; LFM, middle dosage group of licorice flavonoids; LFH, high dosage group of licorice flavonoids.

Figure 6.

The metabolite pathways involved in licorice flavonoids intervention on inflammation. The association between metabolites in groups is depicted in Table 1. The metabolites presented in upward facing trapeziums indicate an increase in levels, whilst those in downward facing trapeziums indicate a decrease in levels following treatment with licorice flavonoids when compared with the model group.