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. 2024 Jan 8:10:1306037.
doi: 10.3389/fnut.2023.1306037. eCollection 2023.

Integrated 16s RNA sequencing and network pharmacology to explore the effects of polyphenol-rich raspberry leaf extract on weight control

Tao Wang  1   2 , Jing Yang  1   2 , Ziang Huang  1   2 , Fei Wang  3 , Ruzi Liu  4 , Yongping Liu  1 , Xiaojun Li  1
Affiliations

Integrated 16s RNA sequencing and network pharmacology to explore the effects of polyphenol-rich raspberry leaf extract on weight control

Tao Wang et al. Front Nutr. .

Abstract

Introduction: Obesity is recognized as a chronic low-grade inflammation associated with intestinal flora imbalance, leading to dyslipidemia and inflammation. Modern research has found that polyphenols have anti-obesity effects. However, the mechanism of action of raspberry leaf extract (RLE) with high polyphenols in regulating obesity is still unknown. This study investigated the improvement effect of supplementing RLE on high-fat diet (HFD) induced obesity in mice.

Methods: RLE was used to intervene in HFD induced C57BL/6J male mice during prevention stage (1-16 weeks) and treatment stage (17-20 weeks). Their weight changes and obesity-related biochemical indicators were measured. The changes in intestinal flora were analyzed using 16S rRNA sequencing, and finally the targets and pathways of the 7 typical polyphenols (quercetin-3-O-glucuronide, ellagic acid, kaempferol-3-O-rutinoside, chlorogenic acid, brevifolin carboxylic acid, quercetin-3-O-rutinoside, and quercetin) of RLE in the regulation of obesity were predicted by network pharmacology approach.

Results and discussion: The results showed that RLE effectively prevented and treated weight gain in obese mice induced by HFD, alleviated adipocyte hypertrophy, reduced Interleukin-6 and Tumor Necrosis Factor Alpha levels, and improved intestinal flora, especially Muriaculaceae, Alistipes and Alloprevotella, and decreased the Firmicutes/Bacteroidota ratio. Network pharmacology analysis selected 60 common targets for 7 RLE polyphenols and obesity. Combined with protein-protein interaction network, enrichment analysis and experimental results, TNF, IL-6, AKT1, and PPAR were predicted as potential key targets for RLE polyphenols.

Conclusion: The potential mechanism by which polyphenol-rich RLE regulates obesity may be attributed to the specific polyphenols of RLE and their synergistic effects, therefore RLE has a great anti-obesity potential and may be used as a means to alleviate obesity and related diseases.

Keywords: IL-6; Rubus idaeus; TNF-α; intestinal flora; network pharmacology; obesity.

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Conflict of interest statement

RL was employed by Dezhou Yongshengzhai Braised Chicken Group Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of mice grouping.
Figure 2
Figure 2
Effect of RLE in the prevention group on body weight and glucose tolerance in mice fed a high-fat diet. (A,B) Changes in body weight of mice. (C,D) Daily food intake. (E) OGTT. (F) AUC of OGTT. #p < 0.05, P-HFD compared with P-LFD group. *p < 0.05, P-HFD compared with P-HPH group.
Figure 3
Figure 3
Effect of RLE in the prevention group on lipid and inflammatory factor levels in mice fed a high-fat diet. (A–F) Serum levels of TC, TG, LDL-C, HDL-C, IL-6, and TNF-α in mice. #p < 0.05, P-HFD compared with P-LFD group. *p < 0.05, P-HFD compared with P-HPH group.
Figure 4
Figure 4
Effect of RLE in the treatment group on lipid and inflammatory factor levels in mice fed a high-fat diet. (A–F) Serum levels of TC, TG, LDL-C, HDL-C, IL-6, and TNF-α in mice. #p < 0.05, T-HFD compared with T-HPL group. *p < 0.05, T-HFD compared with T-HPH group.
Figure 5
Figure 5
Histological observation of white adipose tissue and H&E staining of liver tissue in the prevention and treatment groups (400× magnification). (A) White adipose tissue. (B) Liver tissue.
Figure 6
Figure 6
Effect of RLE on the composition of intestinal flora in HFD-induced obese mice. (A) Histogram of relative abundance at phylum level. (B) Histogram of relative abundance at genus level.
Figure 7
Figure 7
Overlapping targets and PPI network. (A) 60 overlapping targets of 7 polyphenols in RLE and obesity. (B) PPI network of 7 polyphenols in RLE and 60 overlapping targets of obesity.
Figure 8
Figure 8
GO and KEGG enrichment analysis. (A) GO pathway enrichment analysis. (B) KEGG pathway enrichment analysis.
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