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Integrated 16s RNA sequencing and network pharmacology to explore the effects of polyphenol-rich raspberry leaf
Tao Wang1,2, Jing Yang1,2, Ziang Huang1,2
1School of Chemistry and Chemical Engineering, North University of China, Taiyuan, Shanxi, China.
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.
Insights
Raspberry leaf extract (RLE) effectively combats obesity in mice by improving gut microbiota and reducing inflammation. This polyphenol-rich extract shows significant potential for managing obesity and related health issues.
Area of Science:
- Nutrition Science
- Microbiology
- Pharmacology
Background:
- Obesity is a chronic inflammatory condition linked to gut dysbiosis.
- Polyphenols are recognized for their anti-obesity properties.
- The specific mechanisms of raspberry leaf extract (RLE) in obesity regulation remain unclear.
Purpose of the Study:
- To investigate the efficacy of RLE in ameliorating high-fat diet (HFD)-induced obesity in mice.
- To explore the impact of RLE on intestinal flora and key inflammatory markers.
- To predict the molecular targets and pathways of RLE polyphenols in obesity management.
Main Methods:
- Intervention with RLE in HFD-fed C57BL/6J male mice during prevention and treatment phases.
- Assessment of weight changes and obesity-related biochemical indicators.
- 16S rRNA sequencing for gut microbiota analysis and network pharmacology for polyphenol target prediction.
Main Results:
- RLE administration prevented and treated HFD-induced weight gain and adipocyte hypertrophy.
- RLE reduced levels of Interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α).
- RLE improved gut microbiota composition, decreasing the Firmicutes/Bacteroidota ratio and enriching beneficial bacteria; TNF, IL-6, AKT1, and PPAR identified as key targets.
Conclusions:
- Polyphenol-rich RLE demonstrates significant anti-obesity potential in mice.
- RLE's effects are likely mediated by specific polyphenols and their synergistic actions.
- RLE may serve as a therapeutic strategy for obesity and associated diseases.
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