Passiflora incarnata leaf polyphenol extract attenuates high-fat-diet-induced metabolic syndrome in mice via the gut-liver-adipose axis
In C57BL/6J mice fed a high-fat diet, oral supplementation with P. incarnata polyphenol extract favored reductions in body weight, serum lipids, hepatic steatosis, and inflammatory markers, associated with gut microbiota modulation and upregulation of adipose thermogenic genes; all effects were observed exclusively in a preclinical animal model with no human data.
| Population | Male C57BL/6J mice with metabolic syndrome induced by high-fat diet (HFD, 60% kcal from fat) |
|---|---|
| Intervention | P. incarnata leaf polyphenol extract (PP) by oral gavage at doses of 100 and 400 mg/kg/day for 8 weeks |
| Comparator | Untreated HFD group and standard diet group (negative control) |
| Outcome | Body weight; Serum total cholesterol; Serum triglycerides; Hepatic steatosis (NAFLD score); UCP1 and PGC-1α expression in adipose tissue; Akkermansia muciniphila abundance (microbiota); Fecal short-chain fatty acids (SCFAs) |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Body weight | direction favorable vs HFD; exact MD and 95% CI not reported | — | Very low | — | 1 studies |
| Serum total cholesterol | direction favorable vs HFD; exact MD and 95% CI not reported | — | Very low | — | 1 studies |
| Serum triglycerides | direction favorable vs HFD; exact MD and 95% CI not reported | — | Very low | — | 1 studies |
| Hepatic steatosis (NAFLD score) | direction favorable vs HFD; exact MD and 95% CI not reported | — | Very low | — | 1 studies |
| UCP1 and PGC-1α expression in adipose tissue | upregulation vs HFD; exact fold-change and 95% CI not reported | — | Very low | — | 1 studies |
| Akkermansia muciniphila abundance (microbiota) | enrichment vs HFD; exact values and 95% CI not reported | — | Very low | — | 1 studies |
| Fecal short-chain fatty acids (SCFAs) | increase vs HFD; exact values and 95% CI not reported | — | Very low | — | 1 studies |
Context
High-fat-diet-induced metabolic syndrome is an established experimental model for nutritional interventions. Plant polyphenols modulate the microbiota-metabolism-adipose axis, but most evidence remains preclinical. P. incarnata has characterized polyphenolic composition, but its integrated mechanism on the gut-liver-adipose axis had not been systematically evaluated.
What the study showed
The high-dose PP group (400 mg/kg/day) showed body weight reduction relative to the HFD group, with decreases in serum TC, TG, and LDL and increases in HDL; absolute numerical data with 95% CI were not systematically reported for most outcomes in the available text. Microbiota analysis showed enrichment of Akkermansia muciniphila and increased fecal SCFAs, associated with upregulation of UCP1 and PGC-1α in white adipose tissue. Hepatic transcriptomics and fecal metabolomics suggested activation of AMPK/PGC-1α and TGR5/cAMP/PKA pathways, without direct causal relationships being established.
How it was done
Preclinical experimental study in male C57BL/6J mice divided into groups (standard diet, HFD, HFD + PP 100 mg/kg, HFD + PP 400 mg/kg) for 8 weeks; integrated multi-omics approach including fecal 16S rRNA sequencing, untargeted fecal metabolomics, hepatic transcriptomics, and targeted gene expression analysis in adipose tissue. Network pharmacology was used to identify candidate molecular targets prior to animal experiments.
Effect magnitude
Precise effect sizes with 95% CI were not systematically provided in the available text; magnitude of between-group differences was reported primarily as statistically significant without standardized effect values (SMD, RR, or OR).
Risk of bias
Exclusively animal model (mice), with no human data — direct clinical generalization is impossible. The multi-omics approach generates associative hypotheses and does not establish causality between microbiota, metabolites, and metabolic effects. No formal preclinical risk-of-bias tool (SYRCLE or equivalent) was reported; sample size per group was not clearly specified in the available text.
What this study does NOT prove
This study does not prove efficacy or safety in humans, nor does it establish causality between gut microbiota modulation and the observed metabolic effects. Results are not generalizable to human populations with metabolic syndrome.
In clinical practice
This study does not support clinical recommendation of P. incarnata for metabolic syndrome treatment in humans. Clinicians should treat the findings as preclinical mechanistic hypothesis generation. Any therapeutic decision requires evidence from randomized controlled trials.
Limitations
Exclusively animal model (mice), with no human data — direct clinical generalization is impossible. The multi-omics approach generates associative hypotheses and does not establish causality between microbiota, metabolites, and metabolic effects. No formal preclinical risk-of-bias tool (SYRCLE or equivalent) was reported; sample size per group was not clearly specified in the available text.
What is still missing
Randomized controlled trials in humans with metabolic syndrome are needed to evaluate efficacy and safety of P. incarnata extracts. Dose-response studies, oral bioavailability, and pharmacological interactions in humans are similarly absent.
Technical appendix
Version history
- 1.0 · 2026-10-02 — Auto-generated under Evidence Standard v1.0