In this
paper, the
antitussive and
expectorant activity of platycodin D (PD) were studied by constructing a
mouse cough induced by concentrated
ammonia water and a
mouse trachea phenol red excretion model. The mechanism of
antitussive and
expectorant effect of PD was studied by
metabolomics. The
animal experiment was approved by the
Animal Ethics Committee of Jiangxi
University of
Chinese Medicine (approval number JZLLSC-20220739). Then
mice were randomly divided into the normal, model, positive
drug, PD low-
dose, PD medium-
dose and PD high-
dose group. The
antitussive and
expectorant effects of PD were evaluated using a
cough mouse model induced by concentrated
ammonia water and a
mouse tracheal
phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of
mouse lung tissue, and multivariate
statistical analysis method of orthogonal partial
least squares discriminant analysis (OPLS-DA) was used for metabolites profile
analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative
method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of
cough mice induced by
ammonia water, reduce the
coughs frequency, and significantly increase (P < 0.05) the amount of
phenol red excretion in
phenol red excretion model
mice. PD could regulate 6
metabolic pathways of
phenylalanine,
tyrosine and
tryptophan biosynthesis,
linoleic acid metabolism,
phenylalanine metabolism,
glycerophospholipid metabolism, and
tyrosine metabolism to exert
antitussive effect. It could also regulate 8
metabolic pathways of
linoleic acid metabolism, glyoxylic
acid and dicarboxylic
acid metabolism,
glycerol phospholipid metabolism,
citric acid cycle and
arachidonic acid metabolism to exert an
expectorant effect. However, only
linoleic acid metabolism and
glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the
intestinal microbiota. Functional
analysis showed that these
metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory
response, immune function
regulation,
neurotransmitter release,
cell signal transduction,
energy metabolism and
cell apoptosis. This study shows that PD possesses good
antitussive and
expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and
intestinal microbiota could exert an important effect on the
antitussive and
expectorant mechanism of the platycosides.