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An Analysis of the Intestinal Microbiome Combined with Metabo-lomics to Explore the Mechanism of How Pangxiejiao Tea Improves Metabolic Disorders in HFFD-Treated Rats

ABSTRACT:

The high-fat and high-fructose diet(HFFD) can lead to various metabolic disorders. Pangxiejiao (PXJ), a natural plant widely used in folk practices, has been found to contain bioactive compounds that exhibit hypoglycemic effects in vitro. However, the potential of PXJ aqueous extract to ameliorate metabolic disorders in vivo and its underlying mechanisms remain unexplored. This study aims to investigate the effects of PXJ on metabolic disorders induced by HFFD in rats. An HFFD was employed to mimic unhealthy dietary habits, while PXJ was administered via oral gavage for 10 weeks. The results demonstrated that PXJ intervention reduced body weight, improved glucose and lipid metabolism, and decreased serum uric acid levels. PXJ alleviated oxidative stress and inflammation, as evidenced by reduced serum levels of IL-1β, IL-6, and TNF-α, along with ameliorated pathological inflammatory manifestations in metabolism-related organs, such as liver, pancreas, and colon. Furthermore, PXJ was found to decrease the Firmicutes/Bacteroidota ratio, modulated gut microbiota composition, and maintain microbial homeostasis. Nontargeted metabolomics analysis identified 39 upregulated metabolites, including hippuric acid, and 9 downregulated metabolites, such as LysoPG(18:2(9Z,12Z)/0:0). Correlation analysis further revealed that PXJ maintains metabolic homeostasis through complex network crosstalk. Specifically, four gut microbial taxa including Alloprevotella and six metabolites , including hippuric acid, demonstrated significant negative correlations with IL-6, TNF-α , and MDA. In contrast, Lachnospiraceae_NK4A136_group showed positive correlations with these metabolites and SOD. In conclusion, early and sustained PXJ intervention alleviates HFFD-induced metabolic disorders, which is associated with restored gut microbiota balance, improved metabolism, and reduced inflammation and oxidative stress, demonstrating its potential as a novel functional tea for metabolic disorder prevention.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS12949 | MetaboLights | 2025-09-06

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12949_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS12949_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12949_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS12949_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:Objectives: Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Methods: Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. Results: PNLA reduced percentage of monocytes expressing cytokines: TNF-a by 23% (p=0.048), IL-6 by 25% (p=0.011), IL-1B by 23% (p=0.050), IL-8 by 20% (p=0.066). Pathway analysis identified upstream activation of peroxisomes proliferator-activated receptors (PPARs), sirtuin3, and let7miRNA, KLF15 which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-a, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p=9.14E-09) and mitochondrial dysfunction (p=4.18E-08), while the sirtuin (SIRTs) signalling pathway was activated (p=8.89E-06) which interfere with the pathophysiologic process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and Acetyl-CoA Acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. Conclusion: PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.

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An Analysis of the Intestinal Microbiome Combined with Metabo-lomics to Explore the Mechanism of How Pangxiejiao Tea Improves Metabolic Disorders in HFFD-Treated Rats

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