Abstract

Background: Puerariae Radix (PR), the dried root of Pueraria lobata, is reported to possess therapeutic efficacies against various diseases including obesity, diabetes, and hypertension. Fermentation-driven bioactivation of herbal medicines can result in improved therapeutic potencies and efficacies. Methods: C57BL/6J mice were fed a high-fat diet and fructose in water with PR (400 mg/kg) or PR fermented by Bifidobacterium breve (400 mg/kg) for 10 weeks. Histological staining, qPCR, Western blot, and 16s rRNA sequencing were used to determine the protective effects of PR and fermented PR (fPR) against metabolic dysfunction. Results: Treatment with both PR and fPR for 10 weeks resulted in a reduction in body weight gain with a more significant reduction in the latter group. Lactate, important for energy metabolism and homeostasis, was increased during fermentation. Both PR and fPR caused significant down-regulation of the intestinal expression of the MCP-1, IL-6, and TNF-α genes. However, for the IL-6 and TNF-α gene expressions, the inhibitory effect of fPR was more pronounced (p < 0.01) than that of PR (p < 0.05). Oral glucose tolerance test results showed that both PR and fPR treatments improved glucose homeostasis. In addition, there was a significant reduction in the expression of hepatic gene PPARγ, a key regulator of lipid and glucose metabolism, following fPR but not PR treatment. Activation of hepatic AMPK phosphorylation was significantly enhanced by both PR and fPR treatment. In addition, both PR and fPR reduced adipocyte size in highly significant manners (p < 0.001). Treatment by fPR but not PR significantly reduced the expression of PPARγ and low-density lipoproteins in adipose tissue. Conclusion: Treatment with fPR appears to be more potent than that of PR in improving the pathways related to glucose and lipid metabolism in high-fat diet (HFD)+fructose-fed animals. The results revealed that the process of fermentation of PR enhanced lactate and facilitated the enrichment of certain microbial communities that contribute to anti-obesity and anti-inflammatory activities.

Highlights

  • IntroductionMetabolic dysregulation, which represents a constellation of metabolic abnormalities,

  • Metabolic dysregulation, which represents a constellation of metabolic abnormalities,(e.g., hyperglycemia, hyperinsulinemia, hyperlipidemia, etc.), is a vital indicator of obesity-related diseases such as insulin resistance, type 2 diabetes, and fatty liver disease [1]

  • The results revealed that the process of fermentation of Puerariae Radix (PR) enhanced lactate and facilitated the enrichment of certain microbial communities that contribute to anti-obesity and anti-inflammatory activities

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Summary

Introduction

Metabolic dysregulation, which represents a constellation of metabolic abnormalities,. The probable mechanisms by which the gut microbiota could cause the onset and development of obesity and the related metabolic diseases include: (a) high abundance of carbohydrate-fermenting bacteria which leads to an increased production of short-chain fatty acids (SCFAs), providing an extra source of energy for the host in the form of stored lipids or glucose; (b) augmented intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that trigger low-grade inflammation and insulin resistance; and (c) enhanced activity of the gut endocannabinoid system [23]. A number of our previous studies have shown that the protective effects of several herbal formulations against inflammatory insult and metabolic disorders are mediated via modulation of the gut microbial population [17,24,25,26,27,28,29]. The effects of PR and fPR on the distribution profile of mouse intestinal microbiota were studied in order to elucidate the possible mechanism(s) by which these two herbal formulations may exert their beneficial effects

Herbal Preparation
Animals and Treatment
Immunoblotting
Sequencing of 16S rRNA Gene Amplicon of Fecal Microbiota
Sequence Analysis
2.10. Statistical Analysis
Analysis of fPR Preparation
Anti-Inflammatory
Conclusions
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