Formula-syndrome correlation research on formulas containing Uncaria rhynchophylla intervene hypertension with liver Yang hyperactivity syndrome in rats

The study aims to interpret the formula-syndrome correspondence of pacifying liver-subduing Yang and liver Yang hyperactivity from formulas containing Uncaria rhynchophylla based on metabolomics technology, and establish an efficacy evaluation method for these formulas. The rat model of hypertension with liver Yang hyperactivity syndrome was established by intragastrically administering Fuzi Decoction to spontaneously hypertensive rats. Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDZYY20240304033). Tianma Gouteng Decoction, Lingjiao Gouteng Decoction, and Qingnao Jiangya Tablets were respectively administered. The blood pressure, appearance, pain threshold, facial temperature, level of irritability, and 24-hour water intake of the rats were observed. Ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry and metabolomics were used to analyze differential metabolic markers in the serum of rats treated with formulas containing Uncaria rhynchophylla, and metabolic pathway analysis was carried out. Meanwhile the intervention effects of formulas containing Uncaria rhynchophylla were judged according to the changes in the ion intensity of differential metabolites combined with macroscopic data, and partial least squares (PLS) regression analysis was applied to screen significantly differential metabolites. The identified common differential metabolites were regarded as the core metabolic phenotypes of hypertension with liver Yang hyperactivity syndrome. By integrating macroscopic data and metabolic phenotypes, an evaluation method for the syndrome efficacy of Uncaria-based prescriptions was constructed. A total of 35 common differential metabolic markers were identified in this experiment. Among them, 24 differential metabolites decreased in the model group and increased after the intervention of formulas containing Uncaria rhynchophylla, while 11 differential metabolites showed the opposite trend. Metabolic pathway enrichment analysis showed that the intervention pathways were mainly associated with arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis, and glycerophospholipid metabolism. Through PLS regression analysis, 14 significant differential metabolites were obtained, mainly involving three metabolic pathways: arachidonic acid metabolism, biosynthesis of unsaturated fatty acids and glycerophospholipid metabolism. The established efficacy evaluation method indicated that Tianma Gouteng Decoction showed the most significant intervention effect, which was consistent with the theory of traditional Chinese medicine. This study discovered the common factors of formulas containing Uncaria rhynchophylla in intervening hypertension with liver Yang hyperactivity syndrome, and revealed the metabolic basis of the correspondence between these formulas and liver Yang hyperactivity syndrome. The efficacy evaluation method was built to objectively quantify formulas containing Uncaria rhynchophylla, and offers evidence for clinical research.