Safflower extract improves depression in mice by inhibiting the TLR4-NLRP3 inflammation signaling pathway

Chen, Haofan; Ma, Yan; Chen, Miao; Chen, Jianwen; Jin, Chen

doi:10.21037/apm-21-1728

Cited by 13 publications

(7 citation statements)

References 17 publications

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“…It has been reported that stress impairs hippocampal function by inducing the expression of MAPK signaling related proteins, leading to activation of apoptosis and neuronal cell death (Abarikwu and Sunny, 2014;Park et al, 2016). Current studies support that inflammatory cytokines and exposure to psychological acute stressors induce the activation of p38/ JNK in the brain, and that pro-inflammatory cytokine signaling contributes to the pathogenesis of depression (Chen et al, 2021). As downstream effectors of lipopolysaccharide (LPS) stimulation, phosphorylation levels of JNK and p38 in the hippocampus were increased in mice subjected to chronic unpredictable mild stress (Fu et al, 2013;Naeem et al, 2021).…”

Section: Introductionmentioning

confidence: 78%

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

Wenhui

Li²,

Jiang³

et al. 2023

Front. Mol. Neurosci.

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Depression is a common recurrent psychiatric disorder with a high lifetime prevalence and suicide rate. At present, although several traditional clinical drugs such as fluoxetine and ketamine, are widely used, medications with a high efficiency and reduced side effects are of urgent need. Our group has recently reported that a single administration of salmon calcitonin (sCT) could ameliorate a depressive-like phenotype via the amylin signaling pathway in a mouse model established by chronic restraint stress (CRS). However, the molecular mechanism underlying the antidepressant effect needs to be addressed. In this study, we investigated the antidepressant potential of sCT applied chronically and its underlying mechanism. In addition, using transcriptomics, we found the MAPK signaling pathway was upregulated in the hippocampus of CRS-treated mice. Further phosphorylation levels of ERK/p38/JNK kinases were also enhanced, and sCT treatment was able only to downregulate the phosphorylation level of p38/JNK, with phosphorylated ERK level unaffected. Finally, we found that the antidepressant effect of sCT was blocked by p38 agonists rather than JNK agonists. These results provide a mechanistic explanation of the antidepressant effect of sCT, suggesting its potential for treating the depressive disorder in the clinic.

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Section: Introductionmentioning

confidence: 78%

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

Wenhui

Li²,

Jiang³

et al. 2023

Front. Mol. Neurosci.

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“…Another study found that TLR4 activation in the rat hippocampus could induce microglial activation and neuroinflammation, which more directly reflects the relationship between TLR4 and the hippocampus 35 . Previous studies have found that safflower extract could improve depression in mice by inhibiting TLR4/NLRP3 inflammatory signaling pathway 36 . Another study found that inhibition of TLR4 expression could reduce neuroinflammation‐induced depression‐like behavior 37 .…”

Section: Discussionmentioning

confidence: 94%

“…35 Previous studies have found that safflower extract could improve depression in mice by inhibiting TLR4/NLRP3 inflammatory signaling pathway. 36 Another study found that inhibition of TLR4 expression could reduce neuroinflammationinduced depression-like behavior. 37 Therefore, the activation of TLR4 in the CNS may be implicated in the pathophysiological process of some depressive symptoms.…”

Section: Tlr4 Activation Partially Reversed the Inhibition Of N-3 Puf...mentioning

confidence: 99%

n‐3 polyunsaturated fatty acids improve depression‐like behavior by inhibiting hippocampal neuroinflammation in mice via reducing TLR4 expression

Zeng

Yang

et al. 2022

Immunity Inflam & Disease

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Introduction n‐3 polyunsaturated fatty acids (PUFAs) are believed to be implicated in the pathogenesis of many inflammation‐related diseases, including depression. Methods The mouse model of depression was established through chronic unpredictable mild stress (CUMS), the mice were intervened with n‐3 PUFAs, and then the expression of toll‐like receptor 4 (TLR4) was stimulated with lipopolysaccharides (LPS). Tail suspension test (TST), forced swimming test (FST) and sucrose preference test were performed to monitor the depression behavior of mice. Microglia activation was detected by Iba1 immunofluorescence, and neuronal injury was detected by Nissl staining. Concentrations of tumor necrosis factor (TNF)‐α, Interleukin (IL)‐6 and IL‐1β in the hippocampus were assessed via enzyme linked immunosorbent assay (ELISA). Quantitative real time polymerase chain reaction was used to detect IL‐6, IL‐1β and TNF‐α messenger RNA levels. Western blot was utilized for detection of TLR4 protein expression. Results CUMS significantly reduced the sucrose preference in mice, while increased the immobility time in FST and TST. Moreover, CUMS significantly aggravated microglia activation and neuronal damage in mice and increased the levels of IL‐6, IL‐1β and TNF‐α in hippocampal tissues, however, intervention with n‐3 PUFAs could improve the above effects. Further, the increased TLR4 induced by LPS partially reversed the inhibition of n‐3 PUFAs on depression‐like behaviors, microglial activation and inflammatory injury of hippocampal neurons. Conclusion n‐3 PUFAs may ameliorate depression‐like behaviors via reducing hippocampal neuroinflammation in CUMS‐induced mice by regulating TLR4 expression, suggesting that n‐3 PUFAs may be an effective antidepressant, which provides evidence for future treatment of depression.

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“…ameliorated depression by suppressing pyroptosis in animal models. Arctigenin ( Xu et al, 2020 ), safflower extract ( Chen et al, 2021 ), baicalin ( Guo et al, 2019 ), Xiao-Chai-Hu-Tang ( Shao et al, 2021 ), puerarin ( Gao et al, 2021 ), etc. alleviated depression through TLR4 signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory pathophysiological mechanisms implicated in postpartum depression

2022

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Postpartum Depression (PPD) is a serious psychiatric disorder of women within the first year after delivery. It grievously damages women’s physical and mental health. Inflammatory reaction theory is well-established in depression, and also has been reported associated with PPD. This review summarized the inflammatory pathophysiological mechanisms implicated in PPD, including decreased T cell activation, increased proinflammatory cytokines secretion, active kynurenine pathway, and initiated NLRP3 inflammasome. Clinical and preclinical research are both gathered. Potential therapeutical alternatives targeting the inflammatory mechanisms of PPD were introduced. In addition, this review briefly discussed the differences of inflammatory mechanisms between PPD and depression. The research of inflammation in PPD is limited and seems just embarking, which indicates the direction we can further study. As a variety of risky factors contribute to PPD collectively, therapy for women with PPD should be comprehensive, and clinical heterogeneity should be taken into consideration. As PPD has a predictability, early clinical screening and interventions are also needed. This review aims to help readers better understand the inflammatory pathological mechanisms in PPD, so as to identify biomarkers and potential therapeutic targets in the future.

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Safflower extract improves depression in mice by inhibiting the TLR4-NLRP3 inflammation signaling pathway

Cited by 13 publications

References 17 publications

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

n‐3 polyunsaturated fatty acids improve depression‐like behavior by inhibiting hippocampal neuroinflammation in mice via reducing TLR4 expression

Inflammatory pathophysiological mechanisms implicated in postpartum depression

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