Mechanism of Tianma-Gouteng granules lowering blood pressure based on the bile acid-regulated Farnesoid X Receptor-Fibroblast Growth Factor 15- Cholesterol 7α-hydroxylase pathway

Abstract

Ethnopharmacological relevance: Tianma-Gouteng granules (TGG) is a traditional Chinese medicine (TCM) compound that was first recorded by modern medical practitioner Hu Guangci in "New Meaning of the Treatment of Miscellaneous Diseases in Traditional Chinese Medicine". It is widely used to treat hypertensive vertigo, headache and insomnia.

Aim of study: To investigate the antihypertensive effect of TGG and explore its mechanism.

Materials and methods: Spontaneously hypertensive rats (SHR) were prepared a model of the ascendant hyperactivity of liver yang syndrome (AHLYS), blood pressure and general state of rats were recorded. A series of experiments were performed by enzyme-linked immunosorbent assay (ELISA), ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), 16S rRNA sequencing, real-time fluorescence quantitative PCR (RT-qPCR), and enzymatic colorimetry.

Results: TGG can effectively lower blood pressure and improve related symptoms. TGG significantly reduced the levels of IL-1β, IL-6, TNF-α, Renin and AngII. A total of 17 differential metabolites were found in plasma, with the two most potent metabolic pathways being glycerophospholipid metabolism and primary bile acid biosynthesis. After TGG intervention, 7 metabolite levels decreased and 10 metabolite levels increased. TGG significantly increased the relative abundance of Desulfovibio, Lachnoclostridium, Turicibacter, and decreased the relative abundance of Alluobaculum and Monoglobu. TGG also downregulated Farnesoid X Receptor (FXR) and Fibroblast Growth Factor 15 (FGF15) levels in the liver and ileum, upregulated Cholesterol 7α-hydroxylase (CYP7A1) levels, and regulated total bile acid (TBA) levels.

Conclusion: TGG can regulate bile acid metabolism through liver-gut axis, interfere with related intestinal flora and plasma metabolites, decrease blood pressure, and positively influence the pathologic process of SHR with AHLYS. When translating animal microbiota findings to humans, validation studies are essential to confirm reliability and applicability, particularly through empirical human research.

Keywords: Bile acid; CYP7A1; FGF15; FXR; Hypertension; Liver-gut axis; Tianma-Gouteng granules.