Effects of Puerarin on Behavior and Intestinal Bacterial Metabolites of Mice in a Depression-causing Model of Lipopolysaccharide
Objective To investigate the impacts of puerarin on depression induced by lipopolysac-charide in mice and on contents of short-chain fatty acids derived from intestinal flora.Methods Male ICR mice were divided into 6 groups:normal control group,model group,fluoxetine hydrochloride(10 mg·kg-1)group,puerarin low-dose(50 mg·kg-1)group,puerarin medium-dose(100 mg·kg-1)group and puerarin high-dose(200 mg·kg-1)group.Lipopolysaccharide 1 mg·kg-1 was injected intraper-itoneally after 7 days of administration by gavage.After 24 hours,the anxiety-and depression-like behav-iors of mince were assessed via the sucrose preference test,tail suspension test,forced swimming test and the open field test.HE staining was used to detect pathological changes in colon tissue while metabonomics was adopted to determine the levels of acetic acid,propionic acid,butyric acid,valerate acid,isobutyric acid and isovalerate in the short-chain fatty acids of mice.Results Puerarin could significantly increase sucrose preference,moving distance and numbers of times of standing in mice(P<0.01)while significantly shortening immobility time in the mandatory swimming test and tail suspension test(P<0.01)in middle and high dose groups.Immunohistochemical analysis of colons showed that the colon tissue of the lipopolysaccharide model mice was pathologically damaged and showed obvious inflammatory reaction.High-dose puerarin interventions could significantly mitigate the impairment of the intestinal epithelial structure of colon mucosa in mice and reduce inflammatory reactions.Metabonomics analysis showed that the total content of short-chain fatty acids in the model group decreased while the levels of short-chain fatty acids in the puerarin high dose group increased.Conclusion Puerin can improve depres-sion-like behavior induced by inflammation in mice,suggesting that the antidepressant mechanism of puera-rin is closely related to the contents of short-chain fatty acids in intestinal flora.
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