Effects of Eucommia ulmoides-Tribulus terrestris on intestinal microbiota in aged spontaneously hypertensive rats

Objective To observe the effects of the bark of eucommia（Eucommia ulmoides Oliv.） and tribulus terrestris（Tribulus terrestris L.）（ET） on blood pressure and intestinal microbiota in spontaneously hypertensive rats（SHR）. Methods A total of 28 18-month-old male SHR were randomly divided into control group, ET high, medium and low dose group. Rats in four groups were gavaged for 8 weeks. Blood pressure and body weight were measured weekly. Eight weeks later, serum level of N-terminal pro brain natriuretic peptide（NT-proBNP）, neuropeptide Y（NPY）, C reactive protein（CRP）, angiotensin Ⅱ（AngⅡ） and norepinephrine（NE） were measured by enzyme-linked immunosorbent assay（ELISA）, and the expression levels of IKK-α, IKK-β, IκBα and NF-κB p65 were detected by real-time fluorescence quantitative PCR（qRT-PCR）. Stool samples were taken from rats under the aseptic operation principle, and the amplicon information of 16 S V4 region was collected and analyzed. The content of short chain fatty acids（SCFA） in stool samples was detected by gas chromatography. Results The blood pressure of rats in ET high and medium dose group were significantly lower than that of SHR in control group systolic blood pressure/diastolic blood pressure:（170.3±10.7）/（114.0±6.6）,（171.6±10.4）/（112.4±7.3） vs（203.8±11.4）/（136.8±8.0）mm Hg, P＜0.05. Compared with the control group, medium dose of ET significantly decreased the levels of NT-proBNP, NPY, CRP and AngⅡ NT-proBNP:（321.5±31.4） vs（471.7±61.9）ng/L; NPY:（2001.9±26.6） vs（3826.7±68.4）ng/L, CRP:（42.4±13.0） vs（68.5±9.5）mg/L, AngⅡ:（481.9±21.4） vs（591.6±88.7）ng/L, P＜0.05, high dose of ET significantly decreased NPY level （2977.6±64.5） vs（3826.7±68.4）ng/L, P＜0.05. High and medium dose of ET can significantly change the expression of IκBα, IKKβ, NF-κB p65 and IKKα in thoracic aorta. The composition, alpha diversity and beta diversity of intestinal microbiota were significantly different after ET treatment. Anaeroplasma was characteristic microbiota of ET medium dose group at genus level. High and medium dose ET significantly increased the levels of acetic acid and propionic acid in stool samples, while low dose ET significantly increased the levels of butyric acid, isobutyric acid, valeric acid and isovaleric acid. The abundance of anaeroplasma was linearly correlated with CRP concentration（r=-0.85） and NF-κB p65 level（r=-0.78）. Conclusion ET effectively reduced blood pressure and inflammation level in elderly SHR. The mechanism of antihypertension effect may be related to the changes of composition and diversity of intestinal microbiota.