Hypertension, a global chronic noncommunicable disease, exhibits a trend towards younger onset (Whelton et al., 2018) and higher incidence with advancing age (LI et al., 2019). Ascendant hyperactivity of liver yang syndrome (AHLYS) is the most common type, accounting for about 87.3% of hypertension cases in China (LIU, 2022). Tianma-Gouteng granules (TGG) [Composition: Gastrodia elata Blume, Uncaria rhynchophylla (Miq.) Miq.ex Havil, Haliotis diversicolor Reeve, Gardenia jasminoides Ellis, Scutellaria baicalensis Georgi, Achyranthes bidentata Bl., Eucommia ulmoides Oliv., Leonurus japonicus Houtt., Taxillus chinensis (DC.) Danser, Poria Cocos (Schw.) Wolf., Polygonum multiflorum Thunb. The botanical names in TGG have been validated in MPNS (http://mpns.kew.org) and Pharmacopoeia of the People's Republic of China (2020 edition) with a validation date of October 10, 2023.], derived from Tianma-Gouteng decoction, are recommended for AHLYS hypertension, showing a high total effective rate of 90.00% (WANG et al., 2021). TGG effectively controls blood pressure, improves symptoms, and protects target organs, especially in primary and young hypertension cases and hypertensive emergencies. Although its specific mechanism is not fully understood, TGG may reduce reliance on Western medicines, warranting further research (MENG and XIONG, 2020). However, the specific mechanism of the effect of TGG in treating hypertension is still not clear enough, and further research is needed.

Previous studies have mainly explored the antihypertensive effect of Tianma-Gouteng decoction (granules) from the aspects of pharmacodynamics, neuro-endocrine-immune mechanism, genetics and proteomics, but there have been few studies on metabolomics and microbiome. What's more, there are no studies on the combined application of multi-omics. Metabolomics technology emphasizes the holistic study of human body (Zhou et al., 2013), the application of metabolomics methods and techniques in the study of Traditional Chinese Medicine (TCM) compound prescriptions will help interpret the scientific connotation of "symptomatic prescriptions" in the TCM diagnosis (CHEN et al., 2012). Although the efficacy of TGG in the treatment of hypertension is remarkable, but how it works after entering the body, whether changes in the structure of the intestinal flora are involved in the process of its effect is still unclear, combined with the effect of the drug in vivo need to be investigated on the changes in the intestinal flora (OUYANG et al., 2019). Combined application of multi-omics can reveal information about organisms from multiple directions and perspectives, reveal the effects of drugs on organisms, and help discover the pathogenesis of disease itself and the mechanisms of drug treatment (Yang and Hao, 2019). Recent studies have found that the disorder of bile acid metabolism is closely related to the pathogenesis and development of hypertension, but the exact mechanism remains unclear. Therefore, the aim of this study was to investigate the mechanism of TGG treatment for Spontaneously hypertensive rats (SHR) combined with AHLYS by integrating the relevance of gut flora and metabolites at multiple levels through the bile acid pathway.