Geniposide exerts the antidepressant effect by affecting inflammation and glucose metabolism in a mouse model of depression.

Publication date: Aug 02, 2024

Depression is a severe mental illness affecting patient’s physical and mental health. However, long-term effects of existing therapeutic modalities for depression are not satisfactory. Geniposide is an iridoid compound highly expressed in gardenia jasminoides for removing annoyance. The activity of geniposide against depression has been widely studied while most studies concentrated on the expression levels of gene and protein. Herein, the aim of the present study was to employ non-target metabolomic platform of serum to investigate metabolic changes of depression mice and further verify in hippocampus for analyzing the antidepressant mechanism of geniposide. Then we discovered that 9 metabolites of serum were significantly increased in depressive group (prostaglandin E2, leukotriene C4, arachidonic acid, phosphatidylcholine (PC, 16:0/16:0), LysoPC (18:1(9Z)/0:0), phosphatidylethanolamine (14:0/16:0), creatine, oleamide and aminomalonic acid) and 6 metabolites were decreased (indoxylsulfuric acid, testosterone, lactic acid, glucose 6-phosphate, leucine and valine). The levels of arachidonic acid, LysoPC, lactic acid and glucose 6-phosphate in hippocampus were consistent change with serum in depression mice. Most of them showed significant tendencies to be normal by geniposide treatment. Metabolic pathway analysis indicated that arachidonic acid metabolism and glucose metabolism were the main pathogenesis for the antidepressant effect of geniposide. In addition, the levels of serum tumor necrosis factor-α and interleukin-1 were increased in depressive mice and reversed after geniposide treatment. This study revealed that abnormal metabolism of inflammatory response and glucose metabolism of the serum and hippocampus involved in the occurrence of depressive disorder and antidepressant effect of geniposide.

Concepts Keywords
Gardenia chronic mild stress
Mice depression
Necrosis geniposide
Phosphatidylethanolamine hippocampus
Testosterone metabolomic
serum

Semantics

Type Source Name
disease MESH inflammation
disease MESH mental illness
drug DRUGBANK Dinoprostone
drug DRUGBANK Leukotriene C4
drug DRUGBANK Arachidonic Acid
drug DRUGBANK Phosphatidylethanolamine
drug DRUGBANK Creatine
drug DRUGBANK Testosterone
drug DRUGBANK Lactic Acid
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Phosphate ion
drug DRUGBANK L-Leucine
drug DRUGBANK L-Valine
pathway KEGG Arachidonic acid metabolism
disease MESH pathogenesis
disease MESH depressive disorder

Original Article

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