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919 syrup inhibits ROS-mediated leptin-induced anorexia by activating PPARγ and improves gut flora abnormalities - 16/04/21

Doi : 10.1016/j.biopha.2021.111455 
Jing-Wei Xing a, Man-Man Chen b, Xin-Yun Tian a, Dan-Qing Pan a, Xiu-Hua Peng c, Peng-Fei Gao a,
a Department of Traditional Chinese Medicine, Jinshan Hospital of Fudan University, Shanghai, China 
b Department of Traditional Chinese Medicine, Huashan Hospital of Fudan University, Shanghai, China 
c Department of Animal Experiments, Shanghai Public Health Clinical Center, Shanghai, China 

Corresponding author.

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Abstract

Background

Women with postpartum psychiatric disorders are prone to severe anorexia. Clinical studies have revealed the efficacy of 919 syrup, a traditional Chinese medicine mixture against postpartum illnesses, such as in regulating maternal mood and improving postpartum anorexia.

Aim

This study investigated the mechanisms through which 919 syrup improved anorexia induced by postpartum stress, focussing on the combined peroxisome proliferator-activated receptor gamma (PPARγ) and leptin signalling pathway, and its effects on the structure of the gut flora.

Methods

Mice were randomly divided into five groups—control group, immobilisation stressed (IS) group (normal saline), pioglitazone (Piog; western medicine control) group, 919 syrup low-dose (TJD; 13.5 g/kg) group, and 919 syrup high-dose (TJG; 27.0 g/kg) group. The control group was housed normally. The other groups received IS for 3 h daily for 21 days. The treatments were initiated following the first postnatal day and were administered by gastric gavage. All mice were sacrificed under anaesthesia on postnatal day 22. Blood, hypothalamus, stomach, and faecal specimens were collected. Gene and protein expression levels of components of the PPARγ–leptin signalling pathway in the serum, hypothalamus, and stomach were determined. Immunofluorescence staining for proopiomelanocortin (POMC), phosphorylated signal transducer and activator of transcription 3 (pSTAT3), and leptin was performed to observe their spatial distributions in the hypothalamus and stomach. 16s rRNA gene sequencing and bioinformatics analysis of fecal specimens were performed.

Results

After IS, postpartum mice showed significantly reduced appetite and body weight, accompanied by abnormalities in the structure of the gut flora. Treatment with 919 syrup (27.0 g/kg) downregulated malondialdehyde and upregulated catalase, glutathione peroxidase, and superoxide dismutase by activating PPARγ, thereby affecting the expression of leptin signalling pathway components (leptin, leptin receptor, pSTAT3, POMC, and cocaine and amphetamine-related transcript and neuropeptide Y), and modulated the gut flora in stressed mice.

Conclusion

919 syrup improved appetite in mice with postnatal stress by activating PPARγ to induce crosstalk with the leptin signalling pathway, this mechanism was similar to that of PPARγ agonists. 919 syrup also improved gut flora structure, and the changes in the relative abundances of the gut flora strongly correlated with the expression levels of PPARγ and leptin pathway components.

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Highlights

919 syrup improves appetite and nutritional status in postnatal stress mice.
Activating peroxisome proliferator-activated receptor γ inhibits the leptin pathway.
919 syrup activates PPARγ to produce crosstalk with ROS-mediated leptin signaling pathway.
919 syrup regulates the predominant gut flora and increases the beneficial bacteria.
The changes of gut microflora can affect appetite related pathways.

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Abbreviations : ROS, PPARγ, IS, Lepr, MDA, CAT, SOD, GSH-Px, POMC, ICR, EDTA, IGF-1, CART, NPY, STAT3, pSTAT3, SDS-PAGE, PVDF, TBST, PBS, ECL, DAPI, i.g., OTU, NMDS, ANOSIM, LEfSe, LDA

Keywords : 919 syrup, Maternal stress, Anorexia, PPARγ, Gut flora


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© 2021  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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