Eucommia ulmoides leaf polyphenols reduce blood pressure and modulate gut microbiota in spontaneously hypertensive rats
EULP (1.25–3.75 mL/kg/day, 4 weeks) favorably reduced systolic blood pressure in SHR rats compared to the model group, with a dose-dependent pattern observed in a preclinical animal model.
| Population | Male SHR rats (10 weeks, SPF, n=8 per group), established genetic hypertension model |
|---|---|
| Intervention | Eucommia ulmoides leaf polyphenols (EULP) by gavage at three doses: 1.25 mL/kg/day (LD), 2.50 mL/kg/day (MD), 3.75 mL/kg/day (HD) for 4 weeks |
| Comparator | Model group (distilled water, untreated SHR) and positive control (nifedipine 6.0 mg/kg/day) |
| Outcome | Systolic blood pressure; Diastolic blood pressure; Serum vascular biomarkers (NO, eNOS, Ang II, ET); Gut microbiota composition (F/B ratio, Akkermansia, Lactobacillus); Fecal short-chain fatty acids (acetate, propionate, butyrate); Oxidative stress (SOD, GSH-Px, MDA); Lipid profile (TC, TG, LDL-C, HDL-C) |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Systolic blood pressure | MD not reported with 95% CI; statistically significant reduction HD vs Model (p<0.05, values not standardized) | — | Very low | — | 1 studies |
| Diastolic blood pressure | MD not reported with 95% CI; statistically significant reduction HD vs Model (p<0.05, values not standardized) | — | Very low | — | 1 studies |
| Serum vascular biomarkers (NO, eNOS, Ang II, ET) | Direction favorable HD vs Model; effect sizes and 95% CI not reported in standardized form | — | Very low | — | 1 studies |
| Gut microbiota composition (F/B ratio, Akkermansia, Lactobacillus) | Reduced F/B ratio and increased SCFA-producing genera in HD vs Model; effect sizes and 95% CI not reported | — | Very low | — | 1 studies |
| Fecal short-chain fatty acids (acetate, propionate, butyrate) | Increased fecal SCFAs in treated vs Model groups; absolute concentrations and 95% CI not standardized | — | Very low | — | 1 studies |
| Oxidative stress (SOD, GSH-Px, MDA) | Favorable direction HD vs Model; effect sizes and 95% CI not reported in standardized form | — | Very low | — | 1 studies |
| Lipid profile (TC, TG, LDL-C, HDL-C) | Favorable direction in treated vs Model groups; absolute values and 95% CI not standardized | — | Very low | — | 1 studies |
Context
Hypertension remains a leading cardiovascular risk factor, and the gut–heart axis represents an emerging therapeutic target. Eucommia ulmoides leaf polyphenols have traditional use in Chinese medicine, but their mechanisms via gut microbiota were poorly characterized. This study integrates 16S rRNA sequencing, global metabolomics, and targeted SCFA quantification in the SHR model.
What the study showed
The HD group showed reduced SBP compared to the model group with a dose-dependent trend; absolute values and 95% CIs were not fully reported. Favorable vascular markers included increased NO and eNOS and reduced Ang II, ET, and NE in HD vs. model. Gut microbiota in HD showed reduced Firmicutes/Bacteroidetes ratio and increased SCFA-producing genera (Akkermansia, Lactobacillus); fecal acetate, propionate, and butyrate concentrations increased in treated vs. model groups. Precise numerical data with CIs were not comprehensively reported.
How it was done
Controlled experimental study, without documented blinding, in male SHR rats (n=8/group, 6 groups total: NC Wistar, Model SHR, PC nifedipine, LD, MD, HD). Four-week gavage intervention after 5-day acclimatation. Analyses included tail-cuff blood pressure, ELISA for serum biomarkers, 16S rRNA sequencing of cecal content, GC-MS for SCFAs, and untargeted metabolomics.
Effect magnitude
Favorable effect on SBP and DBP reduction in HD vs. model group reported as statistically significant; absolute effect sizes (MD, SMD) and 95% CIs were not presented in standardized form — a critical limitation for assessing clinical magnitude.
Risk of bias
Exclusively preclinical study (SHR rats) without application of a formal risk of bias tool (e.g., SYRCLE for animal studies). Samples of n=8 per group provide very limited statistical power. No documented blinding in outcome assessment or formal randomization. Data presented without standardized 95% CIs. Extrapolation to humans is speculative: pharmacokinetics and human-equivalent dose not established.
What this study does NOT prove
This study does not prove antihypertensive efficacy in humans nor establishes causality between gut microbiota modulation and blood pressure reduction — microbiota and metabolomics correlations are associative, not mechanistic. Results are not generalizable to secondary hypertension, women, or other age groups.
In clinical practice
No basis for clinical recommendation in humans exists from this study. Clinicians should await adequately designed clinical trials before considering EULP as an antihypertensive intervention. The study contributes mechanistic hypotheses (microbiota–SCFA–blood pressure axis) for future investigation.
Limitations
Exclusively preclinical study (SHR rats) without application of a formal risk of bias tool (e.g., SYRCLE for animal studies). Samples of n=8 per group provide very limited statistical power. No documented blinding in outcome assessment or formal randomization. Data presented without standardized 95% CIs. Extrapolation to humans is speculative: pharmacokinetics and human-equivalent dose not established.
What is still missing
Randomized clinical trials in hypertensive humans with standardized EULP dose, pharmaceutical form, and duration are required. Pharmacokinetic studies and identification of bioactive intestinal metabolites of EULP in humans are essential intermediate steps.
Technical appendix
Version history
- 1.0 · 2026-10-02 — Auto-generated under Evidence Standard v1.0