Luteolin reduces fear, anxiety, and depression in rats with post-traumatic stress disorder

Abstract

Exposure to severe stress can lead to the development of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). The cause of PTSD is dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and an imbalance of monoamines. Fruits and vegetables contain large amounts of luteolin (LU; 3′,4′,5,7-tetrahydroxylflavone), which has various pharmacological activities such as anti-inflammatory, antioxidant, and anti-allergic effects. We investigated the effects of LU on fear, depression, and anxiety following monoamine imbalance and hyperactivation of the HPA axis in rats exposed to single prolonged stress (SPS). Male rats were dosed with LU (10 and 20 mg/kg) once daily for 14 days after exposure to SPS. Administration of LU reduced fear freezing responses to extinction recall and depression- and anxiety-like behaviors, and suppressed increases in plasma corticosterone and adrenocorticotropic hormone levels. Also, administration of LU restored the increased norepinephrine and decreased serotonin levels in the structures within the fear circuit, medial prefrontal cortex, and hippocampus. Our results showed that administration of LU improved freezing behavior according in a situation-dependent manner, and showed anti-depressant and anxiolytic effects. Thus, LU may be a useful therapeutic agent to prevent traumatic stress such as PTSD.

Network pharmacology analysis of a patented Chinese herbal medicine for alleviating anxiety disorder in in vitro fertilization-embryo transfer

“… 44 Luteolin can also lead to an increase in norepinephrine and decreased serotonin levels in the medial prefrontal cortex and hippocampus, showing antidepressant and anxiolytic effects. 45 In this study, the main active constituents of QUF3 included quercetin, luteolin, sophoranol, kaempferol, and neurotoxin inhibitors, which is consistent with the results of some previous studies.…”

Identification of anti-inflammatory mechanism of action and molecular targets of Hypericum perforatum in the treatment of major depression based on bioinformatics methods and machine learning

“…Kaempferol increases the AKT/β-linked protein cascade in the prefrontal cortex and reduces in ammatory factor levels (Gao, Wang et al 2019, Silva Dos Santos, Gonçalves Cirino et al 2020). Lignocaine reduces IL-6 production by astrocytes, decreases serum levels of IL-6, TNF-α and corticosterone, and increases mature brain-derived neurotrophic factor (BDNF), dopamine and norepinephrine levels to exert antidepressant effects (Achour, Ferdousi et al 2021, Sur andLee 2022). Furthermore, and most notably, the normal neutrophil group was signi cantly higher than the MDD group, defying the norm of the immunoin ammatory doctrine.…”

Luteolin alleviates depression‐like behavior by modulating glycerophospholipid metabolism in the hippocampus and prefrontal cortex of LOD rats

“…13,14 LUT also improves a variety of depression-like behaviors through different pathways. [15][16][17] Our previous studies have suggested that LUT can enhance the brain's transport of folic acid to promote hippocampal neurogenesis and alter the axonal guidance pathway in cerebrospinal fluid to exert its therapeutic effect on LOD. 5,18 Metabolomics technology is considered a valuable tool in the study of central nervous system diseases.…”

“…Studies have shown that LUT has cognitive effects in animal models of cognitive deficits induced by high‐fat diets or aging, mainly related to its pharmacological anti‐inflammatory properties 13,14 . LUT also improves a variety of depression‐like behaviors through different pathways 15–17 . Our previous studies have suggested that LUT can enhance the brain's transport of folic acid to promote hippocampal neurogenesis and alter the axonal guidance pathway in cerebrospinal fluid to exert its therapeutic effect on LOD 5,18 …”